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Sample records for prevent cardiac hypertrophy

  1. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

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    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  2. Raf-mediated cardiac hypertrophy in adult Drosophila

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    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  3. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

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    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy.

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    Diniz, Gabriela Placoná; Huang, Zhan-Peng; Liu, Jianming; Chen, Jinghai; Ding, Jian; Fonseca, Renata Inzinna; Barreto-Chaves, Maria Luiza; Donato, Jose; Hu, Xiaoyun; Wang, Da-Zhi

    2017-12-15

    Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy

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    Kohli, Shrey; Ahuja, Suchit; Rani, Vibha

    2011-01-01

    Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and anti-hypertrophic factors. Thi...

  6. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

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    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Macrophage microRNA-155 promotes cardiac hypertrophy and failure

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    Heymans, Stephane; Corsten, Maarten F.; Verhesen, Wouter; Carai, Paolo; van Leeuwen, Rick E. W.; Custers, Kevin; Peters, Tim; Hazebroek, Mark; Stöger, Lauran; Wijnands, Erwin; Janssen, Ben J.; Creemers, Esther E.; Pinto, Yigal M.; Grimm, Dirk; Schürmann, Nina; Vigorito, Elena; Thum, Thomas; Stassen, Frank; Yin, Xiaoke; Mayr, Manuel; de Windt, Leon J.; Lutgens, Esther; Wouters, Kristiaan; de Winther, Menno P. J.; Zacchigna, Serena; Giacca, Mauro; van Bilsen, Marc; Papageorgiou, Anna-Pia; Schroen, Blanche

    2013-01-01

    Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this

  8. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Zhou, Heng; Xu, Dachun; Shan, Tichao; Zhang, Fan; Guo, Yuan; Chen, Yuguo; Wu, Dawei

    2015-01-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  9. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

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    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  10. Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

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    Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

    2015-08-01

    Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Pharmacological targeting of CDK9 in cardiac hypertrophy.

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    Krystof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, Jirí

    2010-07-01

    Cardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. At the molecular level, growth of cells is linked to intensive transcription and translation. Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of RNA polymerase II and thus stimulates the elongation phase of transcription. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Recent determination of CDK9's crystal structure now allows the development of selective inhibitors and their further optimization in terms of biochemical potency and selectivity. CDK9 may therefore constitute a novel target for drugs against cardiac hypertrophy.

  12. How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial.

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    Blaustein, Mordecai P

    2017-11-01

    Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na + pumps, however, have demonstrated that cardiac ouabain-sensitive α 2 -Na + pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α 2 -Na + pumps and in mice with cardiac-selective knockout or transgenic overexpression of α 2 -Na + pumps. The latter, seemingly paradoxical, findings can be explained by comparing the numbers of available (ouabain-free) high-affinity (α 2 ) ouabain-binding sites in wild-type, knockout, and transgenic hearts. Conversely, hypertrophy was accelerated in α 2 -ouabain-resistant (R) mice in which the normally ouabain-resistant α 1 -Na + pumps were mutated to an ouabain-sensitive (S) form (α 1 S/S α 2 R/R or "SWAP" vs. wild-type or α 1 R/R α 2 S/S mice). Furthermore, transaortic constriction-induced hypertrophy in SWAP mice was prevented/reversed by immunoneutralizing circulating endogenous ouabain (EO). These findings show that EO and its receptor, ouabain-sensitive α 2 , are critical factors in pressure overload-induced cardiac hypertrophy. This complements reports linking elevated plasma EO to hypertension, cardiac hypertrophy, and failure in humans and elucidates the underappreciated role of the EO-Na + pump pathway in cardiovascular disease. Copyright © 2017 the American Physiological Society.

  13. Pharmacological targeting of CDK9 in cardiac hypertrophy

    Czech Academy of Sciences Publication Activity Database

    Kryštof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, J.

    2010-01-01

    Roč. 30, č. 4 (2010), s. 646-666 ISSN 0198-6325 R&D Projects: GA ČR GA204/08/0511; GA ČR GA301/09/1832; GA ČR GA301/08/1649 Institutional research plan: CEZ:AV0Z50380511 Keywords : P-TEFb * cardiac myocyte * cardiac hypertrophy Subject RIV: CE - Biochemistry Impact factor: 10.228, year: 2010

  14. Dance band on the Titanic: biomechanical signaling in cardiac hypertrophy.

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    Sussman, Mark A; McCulloch, Andrew; Borg, Thomas K

    2002-11-15

    Biomechanical signaling is a complex interaction of both intracellular and extracellular components. Both passive and active components are involved in the extracellular environment to signal through specific receptors to multiple signaling pathways. This review provides an overview of extracellular matrix, specific receptors, and signaling pathways for biomechanical stimulation in cardiac hypertrophy.

  15. Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.

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    Fernanda P Prado

    therapeutic targets to prevent heart failure as a consequence of cardiac hypertrophy.

  16. Myocardial uptake of thallium-201 in rat with cardiac hypertrophy

    International Nuclear Information System (INIS)

    Torii, Yukio; Adachi, Haruhiko; Kizu, Akira; Nakagawa, Masao; Ijichi, Hamao

    1985-01-01

    The thallium-201 (TL) has been used in order to diagnose myocardial infarction and ischemia. Although it is well known that TL distributes in the myocardium in proportion to the distribution of coronary blood flow, the biological property of TL in the loaded myocardium remains unclear. We studied the myocardial uptake of TL in rat with cardiac hypertrophy. Experiments were performed in 30 anesthetized rats devided into 3 groups; control group (C,N=14), hypertrophy group (H,N=6) and diltiazem group (D, 0.3 mg/kg/min. IV. N=10). Cardiac hypertrophy was produced with the banding of the ascending aorta. Myocardial blood flow (MBF) was measured by microspheres labeled with Strontium-85. Cardiac weight was increased in H, and both MBF and TL uptake were proportionally increased. MBF was negatively correlated with the extraction fraction in C (r=-0.71), in H (r=-0.66) and in D (r=-0.85), and this relationship in H was significantly different from it in C (p<0.05), but not in D. From these results, we concluded that TL uptake in H is not always dependant on MBF and affected by the altered metabolism of hypertrophied myocardium. (author)

  17. Adiponectin and Cardiac Hypertrophy in Acromegaly.

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    Gurbulak, Sabriye; Akin, Fulya; Yerlikaya, Emrah; Yaylali, Guzin F; Topsakal, Senay; Tanriverdi, Halil; Akdag, Beyza; Kaptanoglu, Bunyamin

    2016-01-01

    Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be

  18. GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

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    Javier Duran

    Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

  19. Association of myocardial cell necrosis with experimental cardiac hypertrophy

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    Revis, N W; Cameron, A J.V.

    1979-01-01

    Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

  20. Mouse models for the study of postnatal cardiac hypertrophy

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    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  1. Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

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    Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

    2004-07-02

    Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

  2. UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

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    Hongmei Lang

    2018-04-01

    Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

  3. Brain renin angiotensin system in cardiac hypertrophy and failure

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    Luciana eCampos

    2012-01-01

    Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

  4. A Systems Biology Approach to Investigating Sex Differences in Cardiac Hypertrophy.

    Science.gov (United States)

    Harrington, Josephine; Fillmore, Natasha; Gao, Shouguo; Yang, Yanqin; Zhang, Xue; Liu, Poching; Stoehr, Andrea; Chen, Ye; Springer, Danielle; Zhu, Jun; Wang, Xujing; Murphy, Elizabeth

    2017-08-19

    Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood. This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin II to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment. RNA sequencing was performed on hearts, and sex differences in mRNA expression at baseline and following hypertrophy were observed, as well as within-sex differences between baseline and hypertrophy. Sex differences in mRNA were substantial at baseline and reduced somewhat with hypertrophy, as the mRNA differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify mRNA networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on PPARα (peroxisome proliferator-activated receptor α). Mouse experiments further showed that acute inhibition of PPARα blocked sex differences in the development of hypertrophy. The data in this study suggest that PPARα is involved in the sex-dimorphic regulation of cardiac hypertrophy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  6. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

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    Gabriele G. Schiattarella

    2018-05-01

    Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  7. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

    2018-01-01

    Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  8. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

    Science.gov (United States)

    Fernandes, T; Soci, U P R; Oliveira, E M

    2011-09-01

    Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  9. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

    Directory of Open Access Journals (Sweden)

    T. Fernandes

    2011-09-01

    Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

  10. Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yao Song

    Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

  11. YY1 Protects Cardiac Myocytes from Pathologic Hypertrophy by Interacting with HDAC5

    Science.gov (United States)

    Dockstader, Karen; McKinsey, Timothy A.

    2008-01-01

    YY1 is a transcription factor that can repress or activate the transcription of a variety of genes. Here, we show that the function of YY1 as a repressor in cardiac myocytes is tightly dependent on its ability to interact with histone deacetylase 5 (HDAC5). YY1 interacts with HDAC5, and overexpression of YY1 prevents HDAC5 nuclear export in response to hypertrophic stimuli and the increase in cell size and re-expression of fetal genes that accompany pathological cardiac hypertrophy. Knockdown of YY1 results in up-regulation of all genes present during fetal development and increases the cell size of neonatal cardiac myocytes. Moreover, overexpression of a YY1 deletion construct that does not interact with HDAC5 results in transcription activation, suggesting that HDAC5 is necessary for YY1 function as a transcription repressor. In support of this relationship, we show that knockdown of HDAC5 results in transcription activation by YY1. Finally, we show that YY1 interaction with HDAC5 is dependent on the HDAC5 phosphorylation domain and that overexpression of YY1 reduces HDAC5 phosphorylation in response to hypertrophic stimuli. Our results strongly suggest that YY1 functions as an antihypertrophic factor by preventing HDAC5 nuclear export and that up-regulation of YY1 in human heart failure may be a protective mechanism against pathological hypertrophy. PMID:18632988

  12. CSI cardiac prevent 2015

    OpenAIRE

    S Ramakrishnan; Manisha Kaushik

    2015-01-01

    The CSI Cardiac Prevent 2015 was held at Hotel Taj Palace, New Delhi, on September 25-27, 2015. The major challenge was to create interest among cardiologists and physicians on preventive cardiology, a neglected area. The theme of the conference was "Innovations in Heart Disease Prevention.′′ This conference included "CSI at WHF Roadmap Workshop, Inauguration Ceremony, scientific program, plenary sessions, Nursing/Dietician track, Industry Exhibition, Social Events," Great India blood pressur...

  13. Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

    Directory of Open Access Journals (Sweden)

    McIver Lauren J

    2009-12-01

    Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

  14. Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Yao

    2017-04-01

    Full Text Available Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model. Gastrodin was found to alleviate the cardiac hypertrophy in both models. Mechanistically, gastrodin attenuated the store-operated Ca2+ entry (SOCE by reducing the expression of STIM1 and Orai1, two key proteins in SOCE, in animal models as well as in cultured cardiomyocyte model. Furthermore, suppressing SOCE by RO2959, Orai1-siRNAs or STIM1-siRNAs markedly attenuated the phenylephrine-induced hypertrophy in cultured cardiomyocyte model. Together, these results showed that gastrodin inhibited cardiac hypertrophy and it also reduced the SOCE via its action on the expression of STIM1 and Orai1. Furthermore, suppression of SOCE could reduce the phenylephrine-induced cardiomyocyte hypertrophy, suggesting that SOCE-STIM1-Orai1 is located upstream of hypertrophy.

  15. Obesity-associated cardiac pathogenesis in broiler breeder hens: Pathological adaption of cardiac hypertrophy.

    Science.gov (United States)

    Chen, C Y; Lin, H Y; Chen, Y W; Ko, Y J; Liu, Y J; Chen, Y H; Walzem, R L; Chen, S E

    2017-07-01

    Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days. AL hens exhibited increased bodyweight, adiposity, absolute and relative heart weight, ventricular hypertrophy, and cardiac protein/DNA ratio by d 21 (P hens (P Hens allowed AL feeding for 70 d exhibited a higher incidence of mortality (40% vs. 10%) in association with ascites, pericardial effusion, and ventricle dilation. A higher incidence of irregular ECG patterns and rhythmicity consistent with persistently elevated systolic blood pressure and ventricle fibrosis were observed in AL hens (P feeding in broiler hens results in maladaptive cardiac hypertrophy that progresses to overt pathogenesis in contractility and thereby increases mortality. Feed restriction provides clear physiological benefit to heart function of adult broiler hens. © 2017 Poultry Science Association Inc.

  16. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Elkhatali, Samya; El-Sherbeni, Ahmed A.; Elshenawy, Osama H. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Abdelhamid, Ghada [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan (Egypt); El-Kadi, Ayman O.S., E-mail: aelkadi@ualberta.ca [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague–Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200 mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography–mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. - Highlights: • We found 19-hydroxy arachidonic acid to protect cardiomyocytes from hypertrophy. • We validated the use of isoniazid as a cardiac 19-hydroxy arachidonic acid inducer. • We found isoniazid to increase protective and inhibit toxic eicosanoides. • We found isoniazid to protect against angiotensin-induced cardiac hypertrophy. • This will help to

  17. Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment

    International Nuclear Information System (INIS)

    Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

    2016-01-01

    Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. - Highlights: • Cardiomyocyte targeted Curcumin/CMC-peptide increases bioavailability of the drug.

  18. Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats

    NARCIS (Netherlands)

    Tian, Xiao-Li; Pinto, Yigal Martin; Costerousse, Olivier; Franz, Wolfgang M.; Lippoldt, Andrea; Hoffmann, Sigrid; Unger, Thomas; Paul, Martin

    2004-01-01

    Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains

  19. Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection.

    Science.gov (United States)

    Zablocki, Daniela; Sadoshima, Junichi

    2013-11-08

    A series of studies conducted 20 years ago, documenting the cardiac hypertrophy phenotype and its underlying signaling mechanism induced by angiotensin II (Ang II) and mechanical stress, showed a remarkable similarity between the effect of the Gαq agonist and that of mechanical forces on cardiac hypertrophy. Subsequent studies confirmed the involvement of autocrine/paracrine mechanisms, including stretch-induced release of Ang II in load-induced cardiac hypertrophy. Recent studies showed that the Ang II type 1 (AT1) receptor is also directly activated by mechanical forces, suggesting that AT1 receptors play an important role in mediating load-induced cardiac hypertrophy through both ligand- and mechanical stress-dependent mechanisms.

  20. CSI cardiac prevent 2015

    Directory of Open Access Journals (Sweden)

    S Ramakrishnan

    2015-01-01

    Full Text Available The CSI Cardiac Prevent 2015 was held at Hotel Taj Palace, New Delhi, on September 25-27, 2015. The major challenge was to create interest among cardiologists and physicians on preventive cardiology, a neglected area. The theme of the conference was "Innovations in Heart Disease Prevention.′′ This conference included "CSI at WHF Roadmap Workshop, Inauguration Ceremony, scientific program, plenary sessions, Nursing/Dietician track, Industry Exhibition, Social Events," Great India blood pressure Survey, and CSI Smart Heart App. A total of 848 delegates/faculties attended this conference against a total of 1140 people registered for the meeting.

  1. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    OpenAIRE

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, ...

  2. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Directory of Open Access Journals (Sweden)

    Chiaki Nagai-Okatani

    Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  3. Ghrelin and its promoter variant associated with cardiac hypertrophy.

    Science.gov (United States)

    Ukkola, O; Pääkkö, T; Kesäniemi, Y A

    2012-07-01

    The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

  4. Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus).

    Science.gov (United States)

    Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias

    2014-05-15

    Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics. © 2014. Published by The Company of Biologists Ltd.

  5. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Torii, Yukio

    1983-01-01

    I studied experimentally the myocardial uptake of 201 Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that 201 Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia. (J.P.N.)

  6. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, H.J.; Ouyang, W.; Liu, J.H.; Sun, Y.G.; Hu, R.; Huang, L.H.; Xian, J.L. [Southern Medical University, Department of Nuclear Medicine, Zhujiang Hospital, Guangzhou, China, Department of Nuclear Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Jing, C.F.; Zhou, M.J. [Sun Yat-Sen University, South China Sea Marine Biotechnology, National Engineering Research Center, Guangzhou, China, National Engineering Research Center, South China Sea Marine Biotechnology, Sun Yat-Sen University, Guangzhou (China)

    2014-04-11

    Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

  7. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    International Nuclear Information System (INIS)

    Sultana, R.; Sultana, N.; Rashid, A.; Rasheed, S.Z.; Ahmed, M.; Ishaq, M.; Samad, A.

    2010-01-01

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  8. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Sultana, R; Sultana, N; Rashid, A; Rasheed, S Z; Ahmed, M; Ishaq, M; Samad, A [Karachi Institute of Heart Diseases, Karachi (Pakistan)

    2010-10-15

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  9. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Slava Malatiali

    2008-01-01

    Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

  10. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

    Science.gov (United States)

    Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

    2015-09-01

    The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

  11. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

    2013-07-15

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

  12. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    International Nuclear Information System (INIS)

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

    2013-01-01

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

  13. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  14. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

  15. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

    Science.gov (United States)

    Egner, Ingrid M; Bruusgaard, Jo C; Gundersen, Kristian

    2016-08-15

    The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei. © 2016. Published by The Company of Biologists Ltd.

  16. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    2008-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

  17. Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

  18. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S.; Krause, T.; van Geel, P. P.; Willenbrock, R.; Pagel, I.; Pinto, Y. M.; Buikema, H.; van Gilst, W. H.; Lindschau, C.; Paul, M.; Inagami, T.; Ganten, D.; Urata, H.

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  19. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  20. Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

    Science.gov (United States)

    Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

    2018-07-01

    The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

  1. Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Hao Su; Marco Pistolozzi; Xingjuan Shi; Xiaoou Sun; Wen Tan

    2017-01-01

    The development of cardiac hypertrophy is a complicated process,which undergoes a transition from compensatory hypertrophy to heart failure,and the identification of new biomarkers and targets for this disease is greatly needed.Here we investigated the development of isoproterenol (ISO)-induced cardiac hypertrophy in an in vitro experimental model.After the induction of hypertrophy with ISO treatment in H9c2 cells,cell surface area,cell viability,cellular reactive oxygen species (ROS),and nitric oxide (NO) levels were tested.Our data showed that the cell viability,mitochondrial membrane potential,and NO/ROS balance varied during the development of cardiac hypertrophy in H9c2 cells.It was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2 (Prdx2) was decreased during the cardiac hypertrophy of H9c2 cells.These results suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2 cells and in the transition from compensated hypertrophy to de-compensated hypertrophy in H9c2 cells,and our findings may have important implications for the management of this disease.

  2. Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

    Directory of Open Access Journals (Sweden)

    Żebrowska Aleksandra

    2017-04-01

    Full Text Available Several studies have suggested that testosterone exerts a growth-promoting effect in the heart. Limited data are available regarding interactions between possible endocrine/paracrine effects in response to exercise training. Therefore, we examined supraphysiological testosterone-induced heart hypertrophy and cardiac insulin-like growth factor (IGF-1 content in sedentary and exercise-trained rats.

  3. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

    1997-08-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

  4. Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Grabner, Alexander; Hermann, Laura; Richter, Beatrice; Schmitz, Karin; Fischer, Dagmar-Christiane; Yanucil, Christopher; Faul, Christian; Haffner, Dieter

    2017-09-01

    Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. 5/6 nephrectomized (5/6 Nx) rats were treated with different doses of calcitriol for 4 or 10 weeks and cardiac expression of FGF23/FGFR4 and activation of calcineurin/NFAT as well as LVH were analyzed. FGFR4 activation and hypertrophic cell growth were studied in cultured cardiac myocytes that were co-treated with FGF23 and calcitriol. In 5/6Nx rats with LVH, we detected elevated FGF23 expression in bone and myocardium, increased cardiac expression of FGFR4 and elevated cardiac activation of calcineurin/NFAT signaling. Cardiac expression levels of FGF23 and FGFR4 significantly correlated with the presence of LVH in uremic rats. Treatment with calcitriol reduced LVH as well as cardiac FGFR4 expression and calcineurin/NFAT activation. Bone and cardiac FGF23 expression were further stimulated by calcitriol in a dose-dependent manner, but levels of intact cardiac FGF23 protein were suppressed by high-dose calcitriol. In cultured cardiac myocytes, co-treatment with calcitriol blocked FGF23-induced activation of FGFR4 and hypertrophic cell growth. Our data suggest that in CKD, cardioprotective effects of calcitriol stem from its inhibitory actions on the cardiac FGF23/FGFR4 system, and based on their counterbalancing effects on cardiac myocytes, high FGF23 and low calcitriol synergistically contribute to cardiac hypertrophy. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  5. Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

    Science.gov (United States)

    2014-01-01

    Background Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Methods Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Results Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Conclusions Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats. PMID:24521405

  6. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

    Science.gov (United States)

    Galán, María; Varona, Saray; Guadall, Anna; Orriols, Mar; Navas, Miquel; Aguiló, Silvia; de Diego, Alicia; Navarro, María A; García-Dorado, David; Rodríguez-Sinovas, Antonio; Martínez-González, José; Rodriguez, Cristina

    2017-09-01

    Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H 2 O 2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

  7. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    International Nuclear Information System (INIS)

    Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

    2013-01-01

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

  8. Cyclin D2 is a critical mediator of exercise-induced cardiac hypertrophy.

    Science.gov (United States)

    Luckey, Stephen W; Haines, Chris D; Konhilas, John P; Luczak, Elizabeth D; Messmer-Kratzsch, Antke; Leinwand, Leslie A

    2017-12-01

    A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1 -/- ), and mice deficient in cyclin D2 (cyclin D2 -/- ). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2 -/- mice. Cardiac function was not impacted in the cyclin D2 -/- mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2 -/- mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

  9. Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.

    Science.gov (United States)

    Apaijai, Nattayaporn; Charoenphandhu, Narattaphol; Ittichaichareon, Jitjiroj; Suntornsaratoon, Panan; Krishnamra, Nateetip; Aeimlapa, Ratchaneevan; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2017-10-31

    Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) ( n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats. © 2017 The Author(s).

  10. Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress.

    Science.gov (United States)

    Feng, Hong; Cao, Jianlei; Zhang, Guangyu; Wang, Yanggan

    2017-07-01

    Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine for in vitro study. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. In in vitro experiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

  11. Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

    Directory of Open Access Journals (Sweden)

    Liming Pan

    Full Text Available This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418 on cardiac hypertrophy caused by aortic banding (AB, phenylephrine (PE or angiotensin II (Ang II in vivo and in vitro.The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM or hypertrophic cardiomyopathy (HCM and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

  12. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

    Science.gov (United States)

    Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-10-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

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

    Directory of Open Access Journals (Sweden)

    Walker LeeAnn

    2002-01-01

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

  14. Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

    Science.gov (United States)

    Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

    2017-10-01

    Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

  15. Accessory papillary muscles and papillary muscle hypertrophy are associated with sudden cardiac arrest of unknown cause.

    Science.gov (United States)

    Uhm, Jae-Sun; Youn, Jong-Chan; Lee, Hye-Jeong; Park, Junbeom; Park, Jin-Kyu; Shim, Chi Young; Hong, Geu-Ru; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

    2015-10-15

    The present study was performed for elucidating the associations between the morphology of the papillary muscles (PMs) and sudden cardiac arrest (SCA). We retrospectively reviewed history, laboratory data, electrocardiography, echocardiography, coronary angiography, and cardiac CT/MRI for 190 patients with SCA. The prevalence of accessory PMs and PM hypertrophy in patients with SCA of unknown cause was compared with that in patients with SCA of known causes and 98 age- and sex-matched patients without SCA. An accessory PM was defined as a PM with origins separated from the anterolateral and posteromedial PMs, or a PM that branched into two or three bellies at the base of the anterolateral or posteromedial PM. PM hypertrophy was defined as at least one of the two PMs having a diameter of ≥1.1cm. In 49 patients (age 49.9±15.9years; 38 men) the cause of SCA was unknown, whereas 141 (age 54.2±16.6years; 121 men) had a known cause. The prevalence of accessory PMs was significantly higher in the unknown-cause group than in the known-cause group (24.5% and 7.8%, respectively; p=0.002) or the no-SCA group (7.1%, p=0.003). The same was true for PM hypertrophy (unknown-cause 12.2%, known-cause 2.1%, p=0.010; no SCA group 1.0%, p=0.006). By logistic regression, accessory PM and PM hypertrophy were independently associated with sudden cardiac arrest of unknown cause. An accessory PM and PM hypertrophy are associated with SCA of unknown cause. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

    Science.gov (United States)

    Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

    2016-04-01

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.

  17. Andrographis paniculata extract attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet fed mice.

    Science.gov (United States)

    Hsieh, You-Liang; Shibu, Marthandam Asokan; Lii, Chong-Kuei; Viswanadha, Vijaya Padma; Lin, Yi-Lin; Lai, Chao-Hung; Chen, Yu-Feng; Lin, Kuan-Ho; Kuo, Wei-Wen; Huang, Chih-Yang

    2016-11-04

    Andrographis paniculata (Burm. f.) Nees (Acanthaceae) has a considerable medicinal reputation in most parts of Asia as a potent medicine in the treatment of Endocrine disorders, inflammation and hypertension. Water extract of A. paniculata and its active constituent andrographolide are known to possess anti-inflammatory and anti-apoptotic effects. Our aim is to identify whether A. paniculata extract could protect myocardial damage in high-fat diet induced obese mice. The test mice were divided into three groups fed either with normal chow or with high fat diet (obese) or with high fat diet treated with A. paniculata extract (2g/kg/day, through gavage, for a week). We found that the myocardial inflammation pathway related proteins were increased in the obese mouse which potentially contributes to cardiac hypertrophy and myocardial apoptosis. But feeding with A. paniculata extract showed significant inhibition on the effects of high fat diet. Our study strongly suggests that supplementation of A. paniculata extract can be used for prevention and treatment of cardiovascular disease in obese patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance.

    Science.gov (United States)

    Arai, Chikako; Arai, Norie; Mizote, Akiko; Kohno, Keizo; Iwaki, Kanso; Hanaya, Toshiharu; Arai, Shigeyuki; Ushio, Simpei; Fukuda, Shigeharu

    2010-12-01

    Trehalose has been shown to evoke lower insulin secretion than glucose in oral saccharide tolerance tests in humans. Given this hypoinsulinemic effect of trehalose, we hypothesized that trehalose suppresses adipocyte hypertrophy by reducing storage of triglyceride and mitigates insulin resistance in mice fed a high-fat diet (HFD). Mice were fed an HFD and given drinking water containing 2.5% saccharide (glucose [Glc], trehalose [Tre], maltose [Mal], high-fructose corn syrup, or fructose [Fru]) ad libitum. After 7 weeks of HFD and saccharide intake, fasting serum insulin levels in the Tre/HFD group were significantly lower than in the Mal/HFD and Glc/HFD groups (P fructose corn syrup/HFD, or Fru/HFD group. Analysis of gene expression in mesenteric adipocytes showed that no statistically significant difference in the expression of monocyte chemoattractant protein-1 (MCP-1) messenger RNA (mRNA) was observed between the Tre/HFD group and the distilled water/standard diet group, whereas a significant increase in the MCP-1 mRNA expression was observed in the Glc/HFD, Mal/HFD, Fru/HFD, and distilled water/HFD groups. Thus, our data indicate that trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in HFD-fed mice by reducing insulin secretion and down-regulating mRNA expression of MCP-1. These findings further suggest that trehalose is a functional saccharide that mitigates insulin resistance. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

    OpenAIRE

    KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

    1997-01-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

  20. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

    OpenAIRE

    Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-01-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats...

  1. Cardiac hypertrophy in chick embryos induced by hypothermia

    International Nuclear Information System (INIS)

    Boehm, C.; Johnson, T.R.; Caston, J.D.; Przybylski, R.J.

    1987-01-01

    A decrease in incubation temperature from 38 to 32 0 C elicits a decrease in chicken embryo size and weight with concomitant heart enlargement if done after day 10 of incubation. When assayed at day 18 of incubation with the hypothermia started on day 11 or 14, evidence is presented that the heart enlargement is an hypertrophy with no detectable hyperplasia. Supporting data are presented for various physical parameters showing increases in heart wet and dry weight, volume, area, wall thickness, and cell size. There was little difference in DNA content and nuclear [ 3 H]thymidine labeling index between hearts of control and hypothermic embryos. Hearts of hypothermic embryos showed a slight increase in water content and considerable increases in RNA, protein, and glycogen content per unit DNA. The average size of polysomes isolated from hypothermic hearts was larger than that of polysomes isolated from controls. Microscopic studies showed no obvious increase in amount of capillary beds, connective tissue, and myocardial cells. Annulate lamellae were found only in myocardial cells of hypothermic embryos in sparse amounts and low frequency but always associated with large deposits of glycogen

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

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

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

  3. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Okin, Peter M; Olsen, Michael H

    2007-01-01

    BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertens......BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction...... risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14...

  4. Novel Sulfur Metabolites of Garlic Attenuate Cardiac Hypertrophy and Remodeling through Induction of Na+/K+-ATPase Expression.

    Science.gov (United States)

    Khatua, Tarak N; Borkar, Roshan M; Mohammed, Soheb A; Dinda, Amit K; Srinivas, R; Banerjee, Sanjay K

    2017-01-01

    Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. However, the molecular basis for the beneficial effect of garlic on the heart is not known. Therefore, the objective of the present study was to (1) investigate the effect of raw garlic on isoproterenol (Iso) induced cardiac hypertrophy (2) find the active metabolites of garlic responsible for the beneficial effect. Cardiac hypertrophy was induced in rats by subcutaneous single injection of Iso 5 mg kg -1 day -1 for 15 days and the effect of garlic (250 mg/kg/day orally) was evaluated. Garlic metabolites in in vivo were identified by LC/MS study. The effect of garlic and its metabolites were evaluated against hypertrophy in H9C2 cells. Garlic normalized cardiac oxidative stress after Iso administration. Cardiac pathology and mitochondrial enzyme activities were improved in hypertrophy heart after garlic administration. Decreased Na + /K + -ATPase protein level that observed in hypertrophy heart was increased after garlic administration. We identified three garlic metabolites in rat serum. To confirm the role of garlic metabolites on cardiac hypertrophy, Na + /K + -ATPase expression and intracellular calcium levels were measured after treating H9C2 cells with raw garlic and two of its active metabolites, allyl methyl sulfide and allyl methyl sulfoxide. Raw garlic and both metabolites increased Na + /K + -ATPase protein level and decreased intracellular calcium levels and cell size in Iso treated H9C2 cells. This antihypertrophic effect of garlic and its sulfur metabolites were lost in H9C2 cells in presence of Na + /K + -ATPase inhibitor. In conclusion, garlic and its active metabolites increased Na + /K + -ATPase in rat heart, and attenuated cardiac hypertrophy and associated remodeling. Our data suggest that identified new garlic metabolites may be useful for therapeutic intervention against cardiac hypertrophy.

  5. Extracellular signal-regulated kinases 1/2 as regulators of cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Michael eMutlak

    2015-07-01

    Full Text Available Cardiac hypertrophy results from increased mechanical load on the heart and through the actions of local and systemic neuro-humoral factors, cytokines and growth factors. These mechanical and neuroendocrine effectors act through stretch, G protein-coupled receptors and tyrosine kinases to induce the activation of a myriad of intracellular signaling pathways including the extracellular signal-regulated kinases 1/2 (ERK1/2. Since most stimuli that provoke myocardial hypertrophy also elicit an acute phosphorylation of the threonine-glutamate-tyrosine (TEY motif within the activation loops of ERK1 and ERK2 kinases, resulting in their activation, ERKs have long been considered promotors of cardiac hypertrophy. Several mouse models were generated in order to directly understand the causal role of ERK1/2 activation in the heart. These models include direct manipulation of ERK1/2 such as overexpression, mutagenesis or knockout models, manipulations of upstream kinases such as MEK1 and manipulations of the phosphatases that depohosphorylate ERK1/2 such as DUSP6. The emerging understanding from these studies, as will be discussed here, is more complex than originally considered. While there is little doubt that ERK1/2 activation or the lack of it modulates the hypertrophic process or the type of hypertrophy that develops, it appears that not all ERK1/2 activation events are the same. While much has been learned, some questions remain regarding the exact role of ERK1/2 in the heart, the upstream events that result in ERK1/2 activation and the downstream effector in hypertrophy.

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

    Directory of Open Access Journals (Sweden)

    Mohammad T. Elnakish

    2015-01-01

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

  7. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

    Science.gov (United States)

    Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2016-11-11

    The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

  8. Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy

    Science.gov (United States)

    Ding, Yuan-Yuan; Li, Jing-Mei; Guo, Feng-Jie; Liu, Ya; Tong, Yang-Fei; Pan, Xi-Chun; Lu, Xiao-Lan; Ye, Wen; Chen, Xiao-Hong; Zhang, Hai-Gang

    2016-01-01

    The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson’s trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes. PMID:27965581

  9. Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse

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    Elena Ulasova

    2013-01-01

    Full Text Available Hypercholesterolemia is a risk factor for the development of hypertrophic cardiomyopathy. Nevertheless, there are few studies aimed at determining the effects of dietary compounds on early or mild cardiac hypertrophy associated with dyslipidemia. Here we describe left ventricular (LV hypertrophy in 12 week-old Apo E−/− hypercholesterolemic mice. The LV end diastolic posterior wall thickness and overall LV mass were significantly increased in Apo E−/− mice compared with wild type (WT controls. Fractional shortening, LV end diastolic diameter, and hemodynamic parameters were unchanged from WT mice. Oral low dose quercetin (QCN; 0.1 µmol QCN/kg body weight for 6 weeks significantly reduced total cholesterol and very low density lipoprotein in the plasma of Apo E−/− mice. QCN treatment also significantly decreased LV posterior wall thickness and LV mass in Apo E−/− mice. Myocardial geometry and function were unaffected in WT mice by QCN treatment. These data suggest that dietary polyphenolic compounds such as QCN may be effective modulators of plasma cholesterol and could prevent maladaptive myocardial remodeling.

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

    Science.gov (United States)

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

    2017-08-01

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

  11. Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

    Science.gov (United States)

    Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

    2016-03-01

    Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Restoration of Circulating MFGE8 (Milk Fat Globule-EGF Factor 8) Attenuates Cardiac Hypertrophy Through Inhibition of Akt Pathway.

    Science.gov (United States)

    Deng, Ke-Qiong; Li, Jing; She, Zhi-Gang; Gong, Jun; Cheng, Wen-Lin; Gong, Fu-Han; Zhu, Xue-Yong; Zhang, Yan; Wang, Zhihua; Li, Hongliang

    2017-10-01

    Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients. Deleting Mfge8 in mice maintained normal heart function at basal level but substantially exacerbated the hypertrophic enlargement of cardiomyocytes, reprogramming of pathological genes, contractile dysfunction, and myocardial fibrosis after aortic banding surgery. In contrast, cardiac-specific Mfge8 overexpression in transgenic mice significantly blunted aortic banding-induced cardiac hypertrophy. Whereas MAPK (mitogen-activated protein kinase) pathways were unaffected in either Mfge8 -knockout or Mfge8 -overexpressing mice, the activated Akt/PKB (protein kinase B)-Gsk-3β (glycogen synthase kinase-3β)/mTOR (mammalian target of rapamycin) pathway after aortic banding was significantly potentiated by Mfge8 deficiency but suppressed by Mfge8 overexpression. Inhibition of Akt with MK-2206 blocked the prohypertrophic effects of Mfge8 deficiency in angiotensin II-treated neonatal rat cardiomyocytes. Finally, administering a recombinant human MFGE8 in mice in vivo alleviated cardiac hypertrophy induced by aortic banding. Our findings indicate that Mfge8 is an endogenous negative regulator of pathological cardiac hypertrophy and may, thus, have potential both as a novel biomarker and as a therapeutic target for treatment of cardiac hypertrophy. © 2017 American Heart Association, Inc.

  13. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

    Science.gov (United States)

    Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-09-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

  14. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

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    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  15. Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

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    Aline Cristina Piratello

    2010-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

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

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    Quan He

    2014-01-01

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

  17. Endurance training in the spontaneously hypertensive rat: conversion of pathological into physiological cardiac hypertrophy.

    Science.gov (United States)

    Garciarena, Carolina D; Pinilla, Oscar A; Nolly, Mariela B; Laguens, Ruben P; Escudero, Eduardo M; Cingolani, Horacio E; Ennis, Irene L

    2009-04-01

    The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228+/-7 versus 251+/-5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased approximately 40%, collagen volume fraction decreased approximately 50%, and capillary density increased approximately 45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100+/-19% versus 41+/-10% and 100+/-8% versus 61+/-9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca(2+) pump was significantly augmented, whereas that of Na(+)/Ca(2+) exchanger was unchanged (93+/-7% versus 167+/-8% and 158+/-13% versus 157+/-7%, sarcoplasmic reticulum Ca(2+) pump and Na(+)/Ca(2+) exchanger in SHR-Cs and SHR-Es, respectively; PEndurance training inhibited apoptosis, as reflected by a decrease in caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage, and normalized calcineurin activity without inducing significant changes in the phosphatidylinositol 3-kinase/Akt pathway. The swimming routine improved midventricular shortening determined by echocardiography (32.4+/-0.9% versus 36.9+/-1.1% in SHR-Cs and SHR-Es, respectively; Pendurance training to convert pathological into physiological hypertrophy improving cardiac performance. The reduction of myocardial fibrosis and calcineurin activity plus the increase in capillary density represent factors to be considered in determining this beneficial effect.

  18. Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

    DEFF Research Database (Denmark)

    Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.

    2006-01-01

    also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system......RNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle....

  19. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

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

    Science.gov (United States)

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

    2009-01-01

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

  1. Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

    Science.gov (United States)

    Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

    2016-01-01

    Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

  2. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  3. Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

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    Shu-ichi Fujita

    Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.

  4. Exploring Regulatory Mechanisms of Atrial Myocyte Hypertrophy of Mitral Regurgitation through Gene Expression Profiling Analysis: Role of NFAT in Cardiac Hypertrophy.

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    Tzu-Hao Chang

    Full Text Available Left atrial enlargement in mitral regurgitation (MR predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown.This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD, and 6 purchased samples from normal subjects (NC. We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1 were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC.Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

  5. Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients.

    Directory of Open Access Journals (Sweden)

    Yuki Fujimura

    Full Text Available Xanthine oxidoreductase (XOR, which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients.Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI, alanine aminotransferase (ALT, HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD, those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF and increased plasma B-type natriuretic peptide (BNP levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages.Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

  6. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Craig Bolte

    Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  7. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

  8. Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

    Science.gov (United States)

    Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

    2017-08-01

    Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus

  9. Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

    Science.gov (United States)

    Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

    2012-01-01

    African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

  10. Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

    Science.gov (United States)

    Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

    2018-05-09

    Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

  11. GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

    International Nuclear Information System (INIS)

    Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

    2005-01-01

    We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

  12. Elevated Levels of Asymmetric Dimethylarginine (ADMA in the Pericardial Fluid of Cardiac Patients Correlate with Cardiac Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Zoltan Nemeth

    Full Text Available Pericardial fluid (PF contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg precursor of NO-synthase (NOS and asymmetric dimethylarginine (ADMA, an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology.L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28 or valve replacement (VR, n = 25 were determined.We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7 ± 4.6 μmol/L vs. 58.1 ± 4.9 μmol/L, p = 0.011, whereas PF ADMA level was higher in VR than CABG (0.9 ± 0.0 μmol/L vs. 0.7 ± 0.0 μmol/L, p = 0.009. L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1 ± 6.6 vs. CABGplasma: 125.4 ± 10.7, p = 0.004; VRPF: 81.7 ± 4.8 vs. CABGPF: 110.4 ± 7.2, p = 0.009. There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015; and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031; and plasma and PF ADMA in VR (r = 0.529, p = 0.003; and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034. The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7 ± 0.5 mm vs. 11.9 ± 0.4 mm, p = 0.000; posterior wall thickness (12.6 ± 0.3 mm vs. 11.5 ± 0.2 mm, p = 0.000; left ventricular (LV mass (318.6 ± 23.5 g vs. 234.6 ± 12.3 g, p = 0.007; right ventricular (RV (33.9 ± 0.9 cm2 vs. 29.7 ± 0.7 cm2, p = 0.004; right atrial (18.6 ± 1.0 cm2 vs. 15.4 ± 0.6 cm2, p = 0.020; left atrial (19.8 ± 1.0 cm2 vs. 16.9 ± 0.6 cm2, p = 0.033 areas. There was a positive correlation

  13. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  14. Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

    Science.gov (United States)

    Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

    2013-01-01

    Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

  15. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

    Science.gov (United States)

    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations.

    Directory of Open Access Journals (Sweden)

    Marie Demion

    Full Text Available RATIONALE: TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. OBJECTIVES: We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/- model. METHODS AND RESULTS: Morpho-functional analysis revealed left ventricular (LV eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. CONCLUSIONS: TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular

  17. Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia.

    Science.gov (United States)

    Nuglozeh, Edem

    2017-07-01

    compelled us to work at the level of hemizygosity. The histological characterisation of left ventricle shows cardiac hypertrophy together with decrease in body mass and alopecia, this compared to the wild type. The immunohistochemical staining of aorta root showed hyperplasia with increased expression and colocalisation of renin and CTGF demonstrating that CTGF may be involved in vascular tone control. Genetic engineering is a noble avenue to investigate the function of new or existing genes. Our data have shown that CTGF transgenic mouse has cardiac and aorta root hypertrophy and abnormal renin accumulation in aorta root as compared to the wild-type animals. The transgenic animals developed alopecia and lean body mass adding two new functions on pre-existing CTGF multiple functions.

  18. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

  19. The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Güínever Eustáquio do Império

    2015-08-01

    Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  1. Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

    Science.gov (United States)

    Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

    2016-01-01

    It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

  2. Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

    Science.gov (United States)

    Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

    2015-09-01

    The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

  3. MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

    Science.gov (United States)

    Ogata, Takehiro; Naito, Daisuke; Nakanishi, Naohiko; Hayashi, Yukiko K; Taniguchi, Takuya; Miyagawa, Kotaro; Hamaoka, Tetsuro; Maruyama, Naoki; Matoba, Satoaki; Ikeda, Koji; Yamada, Hiroyuki; Oh, Hidemasa; Ueyama, Tomomi

    2014-03-11

    The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

  4. Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

    Science.gov (United States)

    Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

    2015-01-01

    YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

  5. Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

    Science.gov (United States)

    Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

    2017-01-01

    Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

  6. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?

    Science.gov (United States)

    Leischik, Roman; Spelsberg, Norman; Niggemann, Hiltrud; Dworrak, Birgit; Tiroch, Klaus

    2014-01-01

    Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the "cardiac fatigue" caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  7. Molecular and cellular characterization of cardiac overload-induced hypertrophy and failure

    NARCIS (Netherlands)

    Umar, Soban

    2009-01-01

    In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover.

  8. Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); J.M. van Gool (Jeanette); M.J.M. Kofflard (Marcel); A.H.J. Danser (Jan); F.J. ten Cate (Folkert)

    2001-01-01

    textabstractThe development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1

  9. [Pressure sensors to prevent cardiac decompensation].

    Science.gov (United States)

    Klug, Didier

    2017-11-01

    Most cases of hospitalisation for heart failure are preceded by episodes of cardiac decompensation. Preventing these episodes would improve quality of life and reduce mortality and treatment costs. The monitoring of intracardiac pressures, using innovative sensors, coupled with telemedicine, offers interesting perspectives. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

    Science.gov (United States)

    Lu, Songhe; Xu, Dezhong

    2013-12-06

    Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism. Copyright © 2013. Published by Elsevier Inc.

  11. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

    Science.gov (United States)

    Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

    2016-01-01

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  12. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

    International Nuclear Information System (INIS)

    Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K.

    2006-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET A receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, β-myosin heavy chain (β-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET A receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and β-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET A receptor as primary determinants of hypertension and cardiac pathology in AhR null mice

  13. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy

    DEFF Research Database (Denmark)

    Hinrichsen, Rebecca; Hansen, A.H.; Haunsø, S.

    2008-01-01

    /6-phosphorylated retinoblastoma protein (pRb) during hypertrophy and expression of an unphosphorylatable pRb mutant impaired hypertrophic growth in cardiomyocytes. Transcription factor E2F was activated by hypertrophic elicitors but activation was impaired by pharmacological inhibition of cyclin D-cdk4...

  14. Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Louise M Burrell

    Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

  15. Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

    2013-07-11

    The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

  16. Exposure to low dose benzo[a]pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish.

    Science.gov (United States)

    Huang, Lixing; Gao, Dongxu; Zhang, Youyu; Wang, Chonggang; Zuo, Zhenghong

    2014-07-15

    Growing evidence indicates that polycyclic aromatic hydrocarbons (PAHs) can lead to cardiac hypertrophy and recent research indicates that exposure to low dose crude oil during early embryonic development may lead to impacts on heart health at later life stages. The aim of this study was to evaluate whether exposure during early life stages to low dose benzo[a]pyrene (BaP), as a high-ring PAH, would lead to cardiac hypertrophy at later life stages. Zebrafish were exposed to low dose BaP until 96 hpf, then transferred to clean water and maintained for a year before histological and molecular biological analysis. Our results showed that exposure to low level BaP during early life stages increased heart weight to body weight ratios and deposited collagen in the heart of adult zebrafish. ANP, BNP and c-Myc were also induced in the heart of adult zebrafish by BaP. These results proved that low level BaP exposure during early life stages caused symptoms similar to cardiac hypertrophy in adult zebrafish. Our results displayed an elevated expression of CdC42, RhoA, p-ERK1, 2 and Rac1. Therefore, the mechanism of the cardiac hypertrophy caused by BaP exposure during early life stages may be through inducing the expression of CdC42, RhoA and Rac1, together with activating ERK1, 2. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Pressure overload stimulated cardiac hypertrophy leads to a rapid decrease in the mRNA for creatine kinase

    International Nuclear Information System (INIS)

    Boheler, K.; Popovich, B.; Dillmann, W.H.

    1987-01-01

    Cardiac hypertrophy (CH) leads to a decrease in creatine kinase (CK) enzymatic activity. To determine if the mRNA for CK also decreases with CH, they performed the following studies. Cardiac RNA was isolated from rats subjected to either abdominal aortic stenosis (AS) or sham surgery. Through Northern blot analysis, total cardiac RNA was quantitated with a CK specific 32 P-labelled cDNA clone. At 3 and 8 days post-constriction, the mRNA for CK decreases by 54.6 +/- 7% and 65.3 +/- 18% respectively, whereas the heart weight increases by 19% and 37% relative to controls. Further studies indicate that CK mRNA also decreases by 41.8% in hypothyroid rats (Tx) but decreases by a total of 68.1% in Tx rats subjected to 8 days of AS. Pressure overload stimulated CH leads to a rapid decrease in CK mRNA in normal and Tx rats. This CK mRNA decrease may account for the decreased efficiency of contraction seen in CH

  18. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

    Czech Academy of Sciences Publication Activity Database

    McDermott-Roe, Ch.; Ye, J.; Ahmed, R.; Sun, X. M.; Serafín, A.; Ware, J.; Bottolo, L.; Muckett, P.; Caňas, X.; Zhang, J.; Rowe, G. C.; Buchan, R.; Lu, H.; Braithwaite, A.; Mancini, M.; Hauton, D.; Martí, R.; García-Arumí, E.; Hubner, N.; Jacob, H.; Serikawa, T.; Zídek, Václav; Papoušek, František; Kolář, František; Cardona, M.; Ruiz-Meana, M.; García-Dorado, D.; Comella, J. X.; Felkin, L. E.; Barton, P. J. R.; Arany, Z.; Pravenec, Michal; Petretto, E.; Sanchis, D.; Cook, S.A.

    2011-01-01

    Roč. 478, č. 7367 (2011), s. 114-118 ISSN 0028-0836 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/08/0166 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular hypertrophy * endonuclease G * mitochondrial dysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 36.280, year: 2011

  19. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  20. Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W

    2017-09-01

    A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were

  1. [Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

    Science.gov (United States)

    Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

    2018-04-28

    To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (Pguinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

  2. Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs.

    Directory of Open Access Journals (Sweden)

    Jihan Xia

    Full Text Available A long-term high-energy diet affects human health and leads to obesity and metabolic syndrome in addition to cardiac steatosis and hypertrophy. Ectopic fat accumulation in the heart has been demonstrated to be a risk factor for heart disorders, but the molecular mechanism of heart disease remains largely unknown. Bama miniature pigs were fed a high-fat, high-sucrose diet (HFHSD for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased body weight (2.73-fold, P<0.01, insulin level (4.60-fold, P<0.01, heart weight (1.82-fold, P<0.05 and heart volume (1.60-fold, P<0.05 compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. Microarray analyses revealed that 1,022 genes were significantly differentially expressed (P<0.05, ≥1.5-fold change, including 591 up-regulated and 431 down-regulated genes in the HFHSD group relative to the control group. KEGG analysis indicated that the observed heart disorder involved the signal transduction-related MAPK, cytokine, and PPAR signaling pathways, energy metabolism-related fatty acid and oxidative phosphorylation signaling pathways, heart function signaling-related focal adhesion, axon guidance, hypertrophic cardiomyopathy and actin cytoskeleton signaling pathways, inflammation and apoptosis pathways, and others. Quantitative RT-PCR assays identified several important differentially expressed heart-related genes, including STAT3, ACSL4, ATF4, FADD, PPP3CA, CD74, SLA-8, VCL, ACTN2 and FGFR1, which may be targets of further research. This study shows that a long-term, high-energy diet induces obesity, cardiac steatosis, and hypertrophy and provides insights into the molecular mechanisms of hypertrophy and fatty heart to facilitate further research.

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

    Directory of Open Access Journals (Sweden)

    Xiong-Zhi Li

    2017-12-01

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

  4. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.

    Science.gov (United States)

    Wang, Zhi; Li, Liaoliao; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2015-08-01

    Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Saragoca, M.A.; Canziani, M.E.; Gil, M.A.; Castiglioni, M.L.; Cassiolato, J.L.; Barbieri, A.; Lima, V.C.; Draibe, S.A.; Martinez, E.E.

    1991-01-01

    In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program

  6. Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

    Science.gov (United States)

    Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2017-08-01

    We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

  7. Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

    Science.gov (United States)

    Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

    2017-07-01

    BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

  8. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload

    NARCIS (Netherlands)

    Shimano, Masayuki; Ouchi, Noriyuki; Nakamura, Kazuto; van Wijk, Bram; Ohashi, Koji; Asaumi, Yasuhide; Higuchi, Akiko; Pimentel, David R.; Sam, Flora; Murohara, Toyoaki; van den Hoff, Maurice J. B.; Walsh, Kenneth

    2011-01-01

    Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial

  9. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

    Science.gov (United States)

    Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

    2012-01-01

    Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

  10. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

    Science.gov (United States)

    Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

    2017-06-01

    Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. R Wave in aVL Lead is a Robust Index of Left Ventricular Hypertrophy: A Cardiac MRI Study.

    Science.gov (United States)

    Courand, Pierre-Yves; Grandjean, Adrien; Charles, Paul; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Boussel, Loïc; Lantelme, Pierre; Harbaoui, Brahim

    2015-08-01

    In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR). In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women. RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients. Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Genetically Modified Mouse Models Used for Studying the Role of the AT2 Receptor in Cardiac Hypertrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Maria D. Avila

    2011-01-01

    Full Text Available The actions of Angiotensin II have been implicated in many cardiovascular conditions. It is widely accepted that the cardiovascular effects of Angiotensin II are mediated by different subtypes of receptors: AT1 and AT2. These membrane-bound receptors share a part of their nucleic acid but seem to have different distribution and pathophysiological actions. AT1 mediates most of the Angiotensin II actions since it is ubiquitously expressed in the cardiovascular system of the normal adult. Moreover AT2 is highly expressed in the developing fetus but its expression in the cardiovascular system is low and declines after birth. However the expression of AT2 appears to be modulated by pathological states such as hypertension, myocardial infarction or any pathology associated to tissue remodeling or inflammation. The specific role of this receptor is still unclear and different studies involving in vivo and in vitro experiments have shown conflicting data. It is essential to clarify the role of the AT2 receptor in the different pathological states as it is a potential site for an effective therapeutic regimen that targets the Angiotensin II system. We will review the different genetically modified mouse models used to study the AT2 receptor and its association with cardiac hypertrophy and heart failure.

  13. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  14. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  15. Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

    Directory of Open Access Journals (Sweden)

    Michel eKINDO

    2012-08-01

    Full Text Available Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi and whether pressure overload-induced left ventricular hypertrophy (LVH might modulate transmural gradients through increased reactive oxygen species (ROS production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group. Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01 and complex IV activity (-57.4%, P<0.05. Mitochondrial hydrogen peroxide (H2O2 production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass, associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%, increased mitochondrial H2O2 production (+86.9 and +73.1%, free radical leak (+27.2% and +36.3% and citrate synthase activity (+27.2% and +36.3% in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02. Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.

  16. Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: the multi-ethnic study of atherosclerosis.

    Science.gov (United States)

    Armstrong, Anderson C; Gjesdal, Ola; Almeida, André; Nacif, Marcelo; Wu, Colin; Bluemke, David A; Brumback, Lyndia; Lima, João A C

    2014-01-01

    Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk. Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities. Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76. Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods. © 2013. This article is a U.S. Government work and is in the public domain in the USA.

  17. Preventive role of Withania somnifera on hyperlipidemia and cardiac ...

    African Journals Online (AJOL)

    and cardiac oxidative stress in streptozotocin induced type. 2 diabetic rats ... Abstract. Purpose: The present study was intended to investigate the preventive role ofWithania somnifera (WS) ..... The authors declare that this work was done by.

  18. Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.

    Directory of Open Access Journals (Sweden)

    Belén Picatoste

    Full Text Available BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1 enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin or vehicle (n=10, each. After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36, alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36 promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.

  19. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  20. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    International Nuclear Information System (INIS)

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-01-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  1. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  2. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

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    Jody Groenendyk

    Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

  3. Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Paulis, L.; Pecháňová, Olga; Zicha, Josef; Krajčírovičová, K.; Barta, A.; Pelouch, V.; Adamcová, M.; Šimko, F.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S11-S16 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA305/08/0139 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypertension * cardiac hypertrophy * collagen Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  4. Prevention of sudden cardiac death in young athletes: controversies and conundrums.

    Science.gov (United States)

    Rowland, Thomas

    2011-01-01

    Strategies for preventing sudden cardiac death in young athletes are predicated on the assumption that: (1) these events reflect pre-existing, clinically silent heart disease, and (2) means for detecting these abnormalities on the pre-participation evaluation are both feasible and accurate. Recent controversy has surrounded both of these presumptions. Some evidence suggests that the myocardial hypertrophy accompanying sports training itself might serve as a substrate for fatal arrhythmias. As well, vigorous debate has arisen over the optimal content of the pre-participation evaluation, particularly regarding the inclusion of routine screening electrocardiograms. As the rarity of these fatal events does not lend itself to an experimental approach, such disagreements are not easily resolved. Consequently, it is expected that decisions regarding approaches to prevention of sudden death in athletes will be dictated largely by region-specific financial, political, and cultural factors. This chapter examines the aetiologies of sudden cardiac death in young athletes as well as the controversies surrounding the prevention of these tragedies. Copyright © 2011 S. Karger AG, Basel.

  5. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  6. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes? [v1; ref status: indexed, http://f1000r.es/3b4

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    Roman Leischik

    2014-05-01

    Full Text Available Background: Exercise-induced arterial hypertension (EIAH leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM, the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037. The spiroergometric results were: maximum oxygen uptake (relative VO2max 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns. Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034 or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019. Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

  7. Differential diagnosis of left ventricular hypertrophy: usefulness of multimodality imaging and tissue characterization with cardiac magnetic resonance.

    Science.gov (United States)

    Izgi, Cemil; Vassiliou, Vassilis; Baksi, A John; Prasad, Sanjay K

    2016-11-01

    Differential diagnosis of asymmetrical left ventricular hypertrophy may be challenging, particularly in patients with history of hypertension. A middle-aged man underwent an echocardiographic examination during workup for hypertension, which unexpectedly showed significant asymmetrical septal hypertrophy and raised suspicion for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance confirmed the asymmetrical hypertrophy. No myocardial late gadolinium contrast enhancement was seen. However, precontrast T1 mapping revealed a low native myocardial T1 value. This was highly suggestive of Anderson-Fabry disease, which was subsequently proved with very low alpha galactosidase enzyme levels and mutation analysis. The case illustrates clinical usefulness of multimodality imaging and the novel tissue characterization techniques for assessment of left ventricular hypertrophy. © 2016, Wiley Periodicals, Inc.

  8. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

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    Xu, Tongyi [Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zhang, Ben [Centre of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Yang, Fan; Cai, Chengliang; Wang, Guokun [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Han, Qingqi, E-mail: handoctor@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zou, Liangjian, E-mail: zouliangjiansh@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2015-05-08

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  9. Garlic extracts prevent oxidative stress, hypertrophy and apoptosis in cardiomyocytes: a role for nitric oxide and hydrogen sulfide

    Science.gov (United States)

    2012-01-01

    Background In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. Methods Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. Results Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. Conclusion These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S. PMID:22931510

  10. Cardiac rehabilitation: an effective secondary prevention intervention.

    Science.gov (United States)

    Milligan, Fiona

    A combination of quantitative and qualitative research was used to determine the effectiveness of a cardiac rehabilitation (CR) programme in a cohort of patients referred to the service at a London hospital. Quantitative data analysis provided evidence of effectiveness of participation in CR in reduced hospital readmission rates and use of recognised pharmacological management strategies. Self-reported physical activity levels and quality of life (QOL) in individuals who participated in the cardiac rehabilitation programme were qualitatively measured with questionnaires. Results provided evidence of benefit in continued participation in exercise. However, there was no evidence of benefit to QOL status post participation at 1 year. A p-value of 0.001 provided significant statistical evidence supporting the hypothesis of benefit in continued participation in exercise in participants following attendance at a cardiac rehabilitation programme. QOL status; a statistically significant p-value of 0.001 rejected the hypothesis (H1) of benefit. This would imply that participation CR programmes does not appear to provide sustained benefits in QOL. A number of moderating variables were suggested as explaining the finding such as homogeneity of respondents, age, mood bias and the timeframe of 1 year between participation in rehabilitation and self-reporting. CR appears to be an effective but time-limited intervention in relation to improvements in QOL. Collaborative working partnerships between specialist interventions, such as CR with chronic disease management strategies may provide greater sustainability of benefits gained from participation in cardiac rehabilitation programmes.

  11. Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation

    Science.gov (United States)

    Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

    2017-01-01

    Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson’s trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR

  12. Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation.

    Science.gov (United States)

    Wang, Bin; Xu, Ming; Li, Wenju; Li, Xiaoli; Zheng, Qiangsun; Niu, Xiaolin

    2017-01-01

    Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson's trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230

  13. Exome Sequencing Identified a Splice Site Mutation in FHL1 that Causes Uruguay Syndrome, an X-Linked Disorder With Skeletal Muscle Hypertrophy and Premature Cardiac Death.

    Science.gov (United States)

    Xue, Yuan; Schoser, Benedikt; Rao, Aliz R; Quadrelli, Roberto; Vaglio, Alicia; Rupp, Verena; Beichler, Christine; Nelson, Stanley F; Schapacher-Tilp, Gudrun; Windpassinger, Christian; Wilcox, William R

    2016-04-01

    Previously, we reported a rare X-linked disorder, Uruguay syndrome in a single family. The main features are pugilistic facies, skeletal deformities, and muscular hypertrophy despite a lack of exercise and cardiac ventricular hypertrophy leading to premature death. An ≈19 Mb critical region on X chromosome was identified through identity-by-descent analysis of 3 affected males. Exome sequencing was conducted on one affected male to identify the disease-causing gene and variant. A splice site variant (c.502-2A>G) in the FHL1 gene was highly suspicious among other candidate genes and variants. FHL1A is the predominant isoform of FHL1 in cardiac and skeletal muscle. Sequencing cDNA showed the splice site variant led to skipping of exons 6 of the FHL1A isoform, equivalent to the FHL1C isoform. Targeted analysis showed that this splice site variant cosegregated with disease in the family. Western blot and immunohistochemical analysis of muscle from the proband showed a significant decrease in protein expression of FHL1A. Real-time polymerase chain reaction analysis of different isoforms of FHL1 demonstrated that the FHL1C is markedly increased. Mutations in the FHL1 gene have been reported in disorders with skeletal and cardiac myopathy but none has the skeletal or facial phenotype seen in patients with Uruguay syndrome. Our data suggest that a novel FHL1 splice site variant results in the absence of FHL1A and the abundance of FHL1C, which may contribute to the complex and severe phenotype. Mutation screening of the FHL1 gene should be considered for patients with uncharacterized myopathies and cardiomyopathies. © 2016 American Heart Association, Inc.

  14. Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

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    Lijun Catherine Liu

    2016-09-01

    Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

  15. Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

    Science.gov (United States)

    Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

    2013-01-01

    Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

  16. Cardiac Cachexia: Perspectives for Prevention and Treatment.

    Science.gov (United States)

    Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

    2017-01-01

    Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

  17. High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

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    Ulises Novoa

    2017-01-01

    Full Text Available Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes.

  18. Screening of young competitive athletes for the prevention of sudden cardiac death with a wireless electrocardiographic transmission device: a pilot study.

    Science.gov (United States)

    Cho, Jae Hyung; Selen, Mats A; Kocheril, Abraham G

    2015-08-11

    The 12-lead electrocardiographic screening for the prevention of sudden cardiac death in young competitive athletes is not cost-effective and thus not routinely recommended. We investigate whether a less expensive wireless electrocardiographic transmission device can be used to screen for the prevention of sudden cardiac death in this population. During pre-participation screening, twenty college football players underwent two electrocardiograms: a conventional 12-lead electrocardiogram and a wireless 9-lead electrocardiogram. We compared several electrocardiographic parameters (QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow-Lyon criteria, ST deviation and corrected QT interval) to determine the correlation. The QRS duration, left ventricular hypertrophy using the Cornell voltage criteria and the Sokolow-Lyon criteria and corrected QT interval exhibited significant correlation between the two types of electrocardiograms (correlation coefficient 0.878, 0.630, 0.770 and 0.847, respectively with P values of 0.01, 0.003, 0.01 and 0.01, respectively). ST deviation in V1 was weakly correlated between the two types of electrocardiograms without statistical significance (correlation coefficient 0.360 with a P value of 0.119). Our newly developed wireless 9-lead electrocardiogram demonstrated significant correlations with a conventional 12-lead electrocardiogram in terms of QRS duration, left ventricular hypertrophy and corrected QT interval.

  19. Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet.

    Science.gov (United States)

    Viana Gonçalves, Igor Cândido; Cerdeira, Cláudio Daniel; Poletti Camara, Eduardo; Dias Garcia, José Antônio; Ribeiro Pereira Lima Brigagão, Maísa; Bessa Veloso Silva, Roberta; Bitencourt Dos Santos, Gérsika

    2017-09-01

    Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed. A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group. In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Causes and prevention of sudden cardiac death in the elderly.

    Science.gov (United States)

    Tung, Patricia; Albert, Christine M

    2013-03-01

    Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

  1. Early exercise training after myocardial infarction prevents contractile but not electrical remodelling or hypertrophy

    NARCIS (Netherlands)

    V. Bito (Virginie); M.C. de Waard (Monique); L. Biesmans (Liesbeth); I. Lenaerts (Ilse); S. Ozdemir (Semir); E.D. van Deel (Elza); Y. Abdel-Mottaleb (Yousra); R. Driesen (Ronald); P. Holemans (Patricia); D.J.G.M. Duncker (Dirk); K.R. Sipido (Karin)

    2010-01-01

    textabstractAims: Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca2+. We investigated whether this represents partial or complete reversal of cellular remodelling. Methods and results: Mice with MI following left coronary

  2. Enalaprilato na prevenção da hipertrofia ventricular esquerda induzida pelo isoproterenol Enalaprilat prevents the left ventricular hypertrophy induced by isoproterenol

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    Eduardo A. S. Costa

    1997-07-01

    Full Text Available OBJETIVO: Avaliar se o enalaprilato, droga inibidora da enzima de conversão da angiotensina I, previne a hipertrofia ventricular esquerda (HVE induzida pelo isoproterenol. MÉTODOS: Foram divididos em 4 grupos, 72 ratos Wistar-EPM: CON controle; ENA, tratados com enalaprilato (1mg/kg via subcutânea (sc por 8 dias; ISO, tratados com isoproterenol (0,3mg/kg via sc/8 dias e ENA+ISO, tratados simultaneamente com ambas as drogas. Em 10 animais de cada grupo foram determinadas a freqüência cardíaca (FC e a pressão arterial (PA e verificado o peso de ventrículo esquerdo (VE. Em 8 animais de cada grupo, fragmento do VE foi corado com hematoxilina-eosina e picro-sírius e preparado para estudo morfométrico e ultra-estrutural, respectivamente, com microscópio de luz e eletrônico. RESULTADOS: Nos grupos estudados (CON, ENA, ISO e ISO+ENA não ocorreram variações na PA. Os grupos ISO e ISO+ENA exibiram aumentos significantes na FC. O grupo ISO apresentou aumento significativo do peso do VE (PU= 0,821g e PS= 0,204g, quando comparado ao grupo CON. O grupo ENA não exibiu modificação de peso do VE quando comparado ao grupo CON (PU= 0,590g e PS= 0,139g. No grupo ENA+ISO (PU= 0,737g e PS= 0,177g constatou-se diferença de peso ao ser comparado aos grupos ISO e CON. A análise morfométrica e ultra-estrutural mostraram que o ISO induziu hipertrofia dos cardiomiócitos e aumento do tecido conjuntivo com depósito de fibras colágenas do tipo I. O enalaprilato associado com isoproterenol atenuou importantemente aquela manifestação. CONCLUSÃO: O enalaprilato inibiu a ação do isoproterenol sobre os cardiomiócitos, evitando parcialmente, na dose utilizada, a HVE e diminuindo também a quantidade de fibras colágenas.PURPOSE: To evaluate whether the enalaprilat, angiotensin I enzyme conversion inhibitor, could prevent the left ventricular hypertrophy (LVH induced by isoproterenol. METHODS: Seventy two adult Wistar-EPM rats were divided into four

  3. The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

    Science.gov (United States)

    Brasil, Girlandia Alexandre; Silva-Cutini, Mirian de Almeida; Moraes, Flávia de Souza Andrade; Pereira, Thiago de Melo Costa; Vasquez, Elisardo Corral; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Lima, Ewelyne Miranda; Biancardi, Vinícia Campana; Maia, June Ferreira; de Andrade, Tadeu Uggere

    We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP 50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP 50 , the lower plateau, and HR range. In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone.

    Science.gov (United States)

    Diniz, Gabriela Placoná; Lino, Caroline Antunes; Moreno, Camila Rodrigues; Senger, Nathalia; Barreto-Chaves, Maria Luiza Morais

    2017-12-01

    It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T 3 for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T 3 treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T 3 -induced cardiomyocyte hypertrophy and reduced HADC4 mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T 3 -induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4. © 2017 Wiley Periodicals, Inc.

  5. Cardiac hypertrophy and structural and metabolic remodeling related to seasonal dormancy in the first annual cycle in tegu lizards.

    Science.gov (United States)

    da Silveira, Lilian Cristina; do Nascimento, Lucas Francisco R; Colquhoun, Alison; Abe, Augusto S; de Souza, Silvia Cristina R

    2013-07-01

    Morpho-functional adjustments in the heart of juvenile tegu lizards (Tupinambis merianae) were analyzed at distinct seasonal periods to investigate how the demands of growth and of energy saving are reconciled during the first annual cycle. The relative ventricular mass (Mv) was 31% and 69% larger in late autumn and winter dormancy, respectively, compared to early autumn. This effect did not persist during unfed arousal, suggesting that protein accumulates in the heart during hypometabolism and is degraded on arousal. Both the hypertrophy and the atrophy were disproportionate in the largest individuals. In contrast, Mv was smaller in lizards that were starved during spring activity compared to fed lizards, this effect being larger in smaller individuals. In late autumn and winter dormancy the spongy myocardium had 8% of the section area covered by lacunary spaces, which expanded after food intake during arousal and reached 29% in spring activity together with higher density of cardiomyocytes. Total and soluble proteins per mass unity were unchanged, and maximum activities of selected enzymes suggest sustained glycolytic and aerobic capacities during hypometabolism. Results indicate that important structural adjustments occur in the heart in anticipation of dormancy, and that the protein balance in the tissue is maintained at winter temperatures ~17°C. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Characteristics of left ventricular hypertrophy estimated by MIBG and BMIPP cardiac scintigraphy in patients undergoing peritoneal dialysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hiroshige; Oda, Hiroshi; Ohno, Michiya; Watanabe, Sachirow; Kotoo, Yasunori; Matsuno, Yukihiko [Gifu Prefectural Hospital (Japan)

    2002-12-01

    Left ventricular hypertrophy (LVH) has been reported as a major factor in morbidity and mortality in chronic dialysis patients. However, cardiovascular mortality in peritoneal dialysis (PD) patients with LVH is substantially similar to that in hemodialysis (HD) patients. The present study sought to study whether sympathetic nerve activity and fatty acid metabolism of the myocardium estimated by {sup 123}I metaiodobenzylguanidine (MIBG) and {sup 123}I {beta}-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy are impaired or not in PD patients with LVH. The underlying disease of 45 PD patients enrolled in this study was chronic glomerulonephritis in all cases. Serum levels of natriuretic peptides (arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP)) and free carnitine and MIBG, BMIPP myocardial scintigraphy and 2-dimensional echocardiography were measured in these 45 PD patients. The following results were obtained. The prevalence of increased left ventricular mass index (LVMI) was 84.4%. LVMI correlated with age, and serum levels of ANP and BNP, and inversely correlated with a heart-to-mediastinum ratio (H/M) estimated by MIBG and BMIPP myocardial scintigraphy. Percentages of the normal image of MIBG and BMIPP measured with a single photon emission computed tomography (SPECT) were 37.8% and 62.2%, respectively. The PD patients showing the diffuse defect of MIBG or BMIPP imaging had the decrease in left ventricular ejection fraction (LVEF). Especially, the serum level of free carnitine was reduced in the PD patients with diffuse defect of BMIPP SPECT. From these results, we concluded that PD patients with LVH showed impaired sympathetic nerve activity and fatty acid metabolism of the myocardium. Metabolic and functional disturbances of the myocardium may influence mortality in PD patients. (author)

  7. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Su Rin Shin

    2016-01-01

    Full Text Available The incidence of acute kidney injury after cardiac surgery (CS-AKI ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

  8. Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

    Science.gov (United States)

    Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

    2011-07-01

    Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

  9. Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

    Science.gov (United States)

    Parvatiyar, Michelle S; Marshall, Jamie L; Nguyen, Reginald T; Jordan, Maria C; Richardson, Vanitra A; Roos, Kenneth P; Crosbie-Watson, Rachelle H

    2015-12-23

    Duchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy. SSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix. SSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion.

    Science.gov (United States)

    Balogun, Kayode A; Cheema, Sukhinder K

    2016-01-01

    Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.

  11. Myocardial hypertrophy in the recipient with twin-to-twin transfusion syndrome

    DEFF Research Database (Denmark)

    Jeppesen, D.L.; Jorgensen, F.S.; Pryds, O.A.

    2008-01-01

    pressure measurements revealed persistent systemic hypertension. Biventricular hypertrophy was demonstrated by echocardiography. Blood pressure normalised after treatment with Nifedipine and the cardiac hypertrophy subsided over the following weeks. A potential contributing mechanism is intrauterine...

  12. Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies

    Directory of Open Access Journals (Sweden)

    Georges N. Kanaan

    2018-04-01

    Full Text Available Glutaredoxin 2 (GRX2, a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Keywords: Human heart, Mitochondria, Oxidative stress, Redox, Cardiac metabolism, Cardiac hypertrophy

  13. Electrocardiographic Measures of Left Ventricular Hypertrophy in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial

    OpenAIRE

    Ernst, Michael E.; Davis, Barry R.; Soliman, Elsayed Z.; Prineas, Ronald J.; Okin, Peter M.; Ghosh, Alokananda; Cushman, William C.; Einhorn, Paula T.; Oparil, Suzanne; Grimm, Richard H.

    2016-01-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up ECGs in 26,376 ALLHAT participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH were examined using continuous and categorical classifications of Cornell voltage. At 2- and 4-years, prevalence of LVH in the C-group (5.57%; 6.14%) was not statistically different from A-group (2-years: 5.47%; p=0.806, 4-years: 6.54%; p=0.857), or...

  14. Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

    Science.gov (United States)

    Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

    2016-08-04

    Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We

  15. Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

    OpenAIRE

    Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

    2010-01-01

    Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

  16. Aldosterone Inhibits the Fetal Program and Increases Hypertrophy in the Heart of Hypertensive Mice

    Science.gov (United States)

    Azibani, Feriel; Devaux, Yvan; Coutance, Guillaume; Schlossarek, Saskia; Polidano, Evelyne; Fazal, Loubina; Merval, Regine; Carrier, Lucie; Solal, Alain Cohen; Chatziantoniou, Christos; Launay, Jean-Marie; Samuel, Jane-Lise; Delcayre, Claude

    2012-01-01

    Background Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of “fetal” gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. Methodology/Principal Findings RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (−75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. Conclusions/Significance Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction of

  17. Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Feriel Azibani

    Full Text Available BACKGROUND: Arterial hypertension (AH induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren with cardiac hyperaldosteronism (AS mice and systemic hypertension (Ren. AS-Ren mice had increased (x2 angiotensin II in plasma and increased (x2 aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70% versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41% in AS-Ren mice (P<0.05 vs Ren. The increase of ANP (x 2.5; P<0.01 mRNA observed in Ren mice was blunted in AS-Ren mice. This non-induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH-induced increase of ßMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001 in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05, an inhibitor of ßMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of β-myosin heavy chain expression through the induction

  18. F-MARC: promoting the prevention and management of sudden cardiac arrest in football

    OpenAIRE

    Kramer, Efraim Benjamin; Dvorak, J; Schmied, C; Meyer, T

    2015-01-01

    Sudden cardiac death is the most common cause of unnatural death in football. To prevent and urgently manage sudden cardiac arrest on the football field-of-play, F-MARC (FIFA Medical and Research Centre) has been fully committed to a programme of research, education, standardisation and practical implementation. This strategy has detected football players at medical risk during mandatory precompetition medical assessments. Additionally, FIFA has (1) sponsored internationally accepted guidelin...

  19. Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat

    International Nuclear Information System (INIS)

    Mollaoglu, Hakan; Gokcimen, Alpaslan; Ozguner, Fehmi; Oktem, Faruk; Koyu, Ahmet; Kocak, Ahmet; Demirin, Hilmi; Gokalp, Osman; Cicek, Ekrem

    2006-01-01

    Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine the effect of CAPE on cadmium (Cd)-induced hypertension and cardiomyopathy in rats. In particular, nitric oxide (NO) may contribute to the pathophysiology of Cd induced cardiac impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels and nitric oxide (NO, a vasodilator) levels were used as markers Cd-induced cardiac impairment and the success of CAPE treatment. Also, the findings have been supported by the histopathologic evidences. The rats were randomly divided into three experimental groups each (12), as follows: the control group, Cd-treated group (Cd) and Cd plus CAPE-treated group (Cd + CAPE). CdCl 2 in 0.9% NaCl was administrated intraperitoneally (i.p.) with a dose of 1 mg/kg/day. CAPE was co-administered i.p. a dose of 10 μM/kg for 15 days. Hypertension was found to be induced by intraperitoneal administration of Cd in a dose of 1 mg/kg/day on the measurements taken 15 days later. MDA levels were increased (p < 0.001) in cardiac tissue and NO levels were decreased (p < 0.05) in serum in the Cd group than those of the control group had. On the other hand, there was a slight difference (increase) in MDA levels in the Cd + CAPE group than the ones in the control group (p < 0.003). In addition, MDA levels were decreased and NO levels were increased in the Cd + CAPE group compared with the Cd group (p < 0.001, p < 0.0001, respectively). As a result, treatment with CAPE significantly reversed the increased lipid peroxidation (LPO) product, MDA, and decreased NO levels in Cd treated animals. In the histopathologic examination, a significant hypertrophy in atrial and ventricular myofibrils was observed in only Cd administered group, in comparison with the control group. There was no statistically significant difference

  20. Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

    DEFF Research Database (Denmark)

    Piepoli, Massimo Francesco; Corrà, Ugo; Benzer, Werner

    2010-01-01

    Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to card......Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR......) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic...... makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all...

  1. Electrocardiographic Measures of Left Ventricular Hypertrophy in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial

    Science.gov (United States)

    Ernst, Michael E.; Davis, Barry R.; Soliman, Elsayed Z.; Prineas, Ronald J.; Okin, Peter M.; Ghosh, Alokananda; Cushman, William C.; Einhorn, Paula T.; Oparil, Suzanne; Grimm, Richard H.

    2016-01-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up ECGs in 26,376 ALLHAT participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH were examined using continuous and categorical classifications of Cornell voltage. At 2- and 4-years, prevalence of LVH in the C-group (5.57%; 6.14%) was not statistically different from A-group (2-years: 5.47%; p=0.806, 4-years: 6.54%; p=0.857), or L-group (2-years: 5.64%; p=0.857, 4-years: 6.50%; p=0.430). Incident LVH followed similarly, with no difference at 2-years for C (2.99%) compared to A (2.57%; p=0.173) or L (3.16%; p=0.605), and at 4-years (C=3.52%, A=3.29%, L=3.71%; p=0.521 C vs A, p=0.618 C vs L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2-years = +3 to -27 μV, ANOVA p=0.8612; 4-years = +10 to -17 μV, ANOVA p=0.9692). We conclude that risk reductions associated with C treatment in secondary endpoints of ALLHAT cannot be attributed to differential improvements in ECG LVH. PMID:27938852

  2. Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

    Directory of Open Access Journals (Sweden)

    Irene Cuadrado

    Full Text Available Inhibition of Extracellular Matrix degradation by nitric oxide (NO induces cardiac protection against coronary ischemia/reperfusion (IR. Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN stimulates enzymatic activation of matrix metalloproteinases (MMPs in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2 knockout (KO mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9, in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF. NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6. The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5, or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.

  3. Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

    Science.gov (United States)

    Cuadrado, Irene; Castejon, Borja; Martin, Ana M; Saura, Marta; Reventun-Torralba, Paula; Zamorano, Jose Luis; Zaragoza, Carlos

    2016-01-01

    Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.

  4. Influence of strength training on cardiac risk prevention in ...

    African Journals Online (AJOL)

    It has widely been shown that exercise, particularly aerobic exercise, has extensive cardioprotective benefits and is an important tool in the prevention of coronary heart disease (CHD). The present investigation aimed to determine the multivariate impact of strength training, designed to prevent the development of CHD, on ...

  5. Prevention of gastrointestinal injury by using glutamine in cardiac surgery

    Directory of Open Access Journals (Sweden)

    С. М. Ефремов

    2015-10-01

    Full Text Available A pilot double-blind, placebo-controlled, randomized study The aim of this study was to evaluate the efficiency of perioperative administration of glutamine to preserve intestinal integrity in patients undergoing cardiac surgery. 24 patients scheduled for elective coronary artery bypass surgery under cardiopulmonary bypass were included in this prospective, randomized, double-blind placebo controlled pilot study. 12 patients were randomized to receive glutamine (20% solution of N(2-L-alanyl-L-glutamine 0.4 g/kg a day, while the remaining 12 patients received an equivalent placebo dose (0.9% solution of NaCl. Infusion of glutamine/placebo was started after the induction of anesthesia and was continued for 24 hours. The primary end-point was dynamics of plasma concentration of a specific marker of intestinal damage, intestinal fatty acid binding protein (I-FABP. The secondary end-points were liver fatty acid binding protein (L-FABP, alpha glutathione s-transferase (aGST, heat shock protein 70 (HSP 70. There were no between-group differences of all the studied biochemical parameters at any stage of the study. Plasma I-FABP levels (median [25-75 percentile] were markedly elevated during CPB and remained the same postoperatively: 962 (577-2 067 and 883 (444-1 625 г/ml 5 min after un-clamping of aorta, 2203 (888-3 429 and 1 560 (506-2 657 г/ml 2 hours post-bypass, 897 (555-1 424 and 794 (505-951 г/ml 6 hours post-bypass in the GLN and control groups respectively. Perioperative administration of glutamine in dose of 0.4 g/kg a day does not appear to preserve intestinal integrity in low risk cardiac surgery patients.

  6. Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

    DEFF Research Database (Denmark)

    Corrà, Ugo; Piepoli, Massimo F; Carré, François

    2010-01-01

    of a healthy lifestyle. These secondary prevention targets are included in the overall goal of cardiac rehabilitation (CR). Cardiac rehabilitation can be viewed as the clinical application of preventive care by means of a professional multi-disciplinary integrated approach for comprehensive risk reduction...... and global long-term care of cardiac patients. The CR approach is delivered in tandem with a flexible follow-up strategy and easy access to a specialized team. To promote implementation of cardiac prevention and rehabilitation, the CR Section of the EACPR (European Association of Cardiovascular Prevention...... and Rehabilitation) has recently completed a Position Paper, entitled 'Secondary prevention through cardiac rehabilitation: A condition-oriented approach'. Components of multidisciplinary CR for seven clinical presentations have been addressed. Components include patient assessment, physical activity counselling...

  7. Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias

    NARCIS (Netherlands)

    Fernandes, Sarah; van Rijen, Harold V. M.; Forest, Virginie; Evain, Stéphane; Leblond, Anne-Laure; Mérot, Jean; Charpentier, Flavien; de Bakker, Jacques M. T.; Lemarchand, Patricia

    2009-01-01

    Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients

  8. Preventing tomorrow's sudden cardiac death today: part I: Current data on risk stratification for sudden cardiac death.

    Science.gov (United States)

    Al-Khatib, Sana M; Sanders, Gillian D; Bigger, J Thomas; Buxton, Alfred E; Califf, Robert M; Carlson, Mark; Curtis, Anne; Curtis, Jeptha; Fain, Eric; Gersh, Bernard J; Gold, Michael R; Haghighi-Mood, Ali; Hammill, Stephen C; Healey, Jeff; Hlatky, Mark; Hohnloser, Stefan; Kim, Raymond J; Lee, Kerry; Mark, Daniel; Mianulli, Marcus; Mitchell, Brent; Prystowsky, Eric N; Smith, Joseph; Steinhaus, David; Zareba, Wojciech

    2007-06-01

    Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.

  9. F-MARC: promoting the prevention and management of sudden cardiac arrest in football.

    Science.gov (United States)

    Kramer, Efraim Benjamin; Dvorak, J; Schmied, C; Meyer, T

    2015-05-01

    Sudden cardiac death is the most common cause of unnatural death in football. To prevent and urgently manage sudden cardiac arrest on the football field-of-play, F-MARC (FIFA Medical and Research Centre) has been fully committed to a programme of research, education, standardisation and practical implementation. This strategy has detected football players at medical risk during mandatory precompetition medical assessments. Additionally, FIFA has (1) sponsored internationally accepted guidelines for the interpretation of an athlete's ECG, (2) developed field-of-play-specific protocols for the recognition, response, resuscitation and removal of a football player having sudden cardiac arrest and (3) introduced and distributed the FIFA medical emergency bag which has already resulted in the successful resuscitation of a football player who had a sudden cardiac arrest on the field-of-play. Recently FIFA, in association with the Institute of Sports and Preventive Medicine in Saarbrücken, Germany, established a worldwide Sudden Death Registry with a view to documenting fatal events on the football field-of-play. These activities by F-MARC are testimony to FIFA's continued commitment to minimising sudden cardiac arrest while playing football. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Preventive role of Withania somnifera on hyperlipidemia and cardiac ...

    African Journals Online (AJOL)

    Purpose: The present study was intended to investigate the preventive role of Withania somnifera (WS) on hyperlipidemia and oxidative stress in the heart of streptozotocin (STZ)-induced type 2 diabetic rats. Methods: Single intraperitoneal injection of STZ (100 mg/kg) was given to 2 days rat pups to induce type 2 diabetes ...

  11. Prevention of cardiac complications in peripheral vascular surgery

    International Nuclear Information System (INIS)

    Cutler, B.S.

    1986-01-01

    The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. Complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. To reduce the incidence of cardiac complications, it is first necessary to identify patients at risk through screening tests. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise

  12. Role of diclofenac in the prevention of postpericardiotomy syndrome after cardiac surgery

    Science.gov (United States)

    Sevuk, Utkan; Baysal, Erkan; Altindag, Rojhat; Yaylak, Baris; Adiyaman, Mehmet Sahin; Ay, Nurettin; Alp, Vahhac; Beyazit, Unal

    2015-01-01

    Objective Postpericardiotomy syndrome (PPS), which is thought to be related to autoimmune phenomena, represents a common postoperative complication in cardiac surgery. Late pericardial effusions after cardiac surgery are usually related to PPS and can progress to cardiac tamponade. Preventive measures can reduce postoperative morbidity and mortality related to PPS. In a previous study, diclofenac was suggested to ameliorate autoimmune diseases. The aim of this study was to determine whether postoperative use of diclofenac is effective in preventing early PPS after cardiac surgery. Methods A total of 100 patients who were administered oral diclofenac for postoperative analgesia after cardiac surgery and until hospital discharge were included in this retrospective study. As well, 100 patients undergoing cardiac surgery who were not administered nonsteroidal anti-inflammatory drugs were included as the control group. The existence and severity of pericardial effusion were determined by echocardiography. The existence and severity of pleural effusion were determined by chest X-ray. Results PPS incidence was significantly lower in patients who received diclofenac (20% vs 43%) (Pdiclofenac had a significantly lower incidence of pericardial effusion (15% vs 30%) (P=0.01). Although not statistically significant, pericardial and pleural effusion was more severe in the control group than in the diclofenac group. The mean duration of diclofenac treatment was 5.11±0.47 days in patients with PPS and 5.27±0.61 days in patients who did not have PPS (P=0.07). Logistic regression analysis demonstrated that diclofenac administration (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.18–0.65, P=0.001) was independently associated with PPS occurrence. Conclusion Postoperative administration of diclofenac may have a protective role against the development of PPS after cardiac surgery. PMID:26170687

  13. Perioperative management for the prevention of bacterial infection in cardiac implantable electronic device placement

    Directory of Open Access Journals (Sweden)

    Katsuhiko Imai

    2016-08-01

    Full Text Available Cardiac implantable electronic devices (CIEDs have become important in the treatment of cardiac disease and placement rates increased significantly in the last decade. However, despite the use of appropriate antimicrobial prophylaxis, CIED infection rates are increasing disproportionately to the implantation rate. CIED infection often requires explantation of all hardware, and at times results in death. Surgical site infection (SSI is the most common cause of CIED infection as a pocket infection. The best method of combating CIED infection is prevention. Prevention of CIED infections comprises three phases: before, during, and after device implantation. The most critical factors in the prevention of SSIs are detailed operative techniques including the practice of proper technique by the surgeon and surgical team.

  14. Recent advances in understanding and prevention of sudden cardiac death [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jamie I. Vandenberg

    2017-08-01

    Full Text Available There have been tremendous advances in the diagnosis and treatment of heart disease over the last 50 years. Nevertheless, it remains the number one cause of death. About half of heart-related deaths occur suddenly, and in about half of these cases the person was unaware that they had underlying heart disease. Genetic heart disease accounts for only approximately 2% of sudden cardiac deaths, but as it typically occurs in younger people it has been a particular focus of activity in our quest to not only understand the underlying mechanisms of cardiac arrhythmogenesis but also develop better strategies for earlier detection and prevention. In this brief review, we will highlight trends in the recent literature focused on sudden cardiac death in genetic heart diseases and how these studies are contributing to a broader understanding of sudden death in the community.

  15. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

    Science.gov (United States)

    Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

    2016-09-01

    Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. Copyright © 2016 the American Physiological Society.

  16. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist. The effect of the αAnalogue on Angiotensin II (AngII)-induced hypertension......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...... failure. It preserved heart function, assessed by echocardiography, whilst protecting against adverse cardiac remodelling and apoptosis. Moreover, treatment with the αAnalogue was well-tolerated with neither signs of desensitisation nor behavioural changes. Conclusions -These findings, in two distinct...

  17. Efficacy of ranolazine in preventing atrial fibrillation following cardiac surgery: Results from a meta-analysis

    Directory of Open Access Journals (Sweden)

    Chintan Trivedi, MD, MPH

    2017-06-01

    Conclusions: Ranolazine may prove beneficial in POAF prevention following cardiac surgeries. Although the pooled treatment effect is quite impressive with a reduction of more than 50% of risk of developing POAF, small number of studies and variation in ranolazine dose regimen in each study make our results inconclusive, but worthy of further investigation. That is why this result has to be interpreted as only hypothesis generating, rather than conclusion drawing.

  18. Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

    Science.gov (United States)

    Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

    2018-03-06

    The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied

  19. Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation

    Science.gov (United States)

    Li, Shu-Hong; Sun, Zhuo; Guo, Lily; Han, Mihan; Wood, Michael F G; Ghosh, Nirmalya; Alex Vitkin, I; Weisel, Richard D; Li, Ren-Ke

    2012-01-01

    After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P elastin showed the greatest functional improvement (P elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration. PMID:22435995

  20. Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

    Science.gov (United States)

    Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

    2017-08-01

    Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  2. Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Sultana, Md Razia; Bagul, Pankaj K; Katare, Parameshwar B; Anwar Mohammed, Soheb; Padiya, Raju; Banerjee, Sanjay K

    2016-11-01

    Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart. Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart. We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts. Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Sudden cardiac death in athletes and its preventive strategies: review article

    Directory of Open Access Journals (Sweden)

    Farzin Halabchi

    2017-12-01

    Full Text Available Sudden cardiac death in sport, although rare, but is a tragic event, attracting the media and public attention. Sport and exercise may act as a trigger for sudden cardiac death. Risk of sudden death in young athletes with cardiovascular disease is 2.5 times more frequent than non-athlete individuals. More than 90% of cases of sudden death occur during or immediately after training or competition. Incidence of sudden cardiac death in any population, including athletes, is related to multiple factors such as gender, age, race, nationality, diagnostic screening methods and preventive measures for sudden cardiac death. Otherwise, incidence rate of sudden cardiac death is linked to the used definition and method of diagnosis. Different cardiovascular disorders may result in death of young athletes and hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia and aortic rupture are among the most common causes. Marfan syndrome, dilated cardiomyopathy, viral myocarditis, Wolff-Parkinson-White (WPW syndrome, congenital long QT syndrome, Brugada syndrome and commotio cordis are reported as other etiologies. In older athletes (more than 35 years, ischemic coronary heart disease is responsible for majority of the cases similar to the general population. Because the outcome of sudden cardiac arrest in sports is very poor except in few cases, proper national strategies are needed to diminish the burden of sudden death in young athletes. It seems that there are two main strategies to achieve this goal: A Primary prevention with use of purposeful pre-participation evaluation programs. This evaluation should focuss on the proper history and physical examination. Nevertheless, there is significant debate between American and European countries regarding the use of paraclinical investigations (especially ECG. American heart association does not recommend ECG as an essential part of evaluation. In contrast, European

  4. Cardiomyopathies as a Cause of Sudden Cardiac Death (SCD in Egypt: Recognition and Preventive Strategies Needed

    Directory of Open Access Journals (Sweden)

    Nora Fnon

    2016-06-01

    Full Text Available This study aimed at evaluating the epidemiological characteristics and pathological features of different types of cardiomyopathies in Egypt, highlighting the role of the forensic pathologist in identifying cases of cardiomyopathies and initiating for their families a possible genetic study aiming at prevention of sudden death. All cases with sudden cardiac death (SCD due to cardiomyopathies during the period from the beginning of January 2010 until the end of December 2014 (5 years were included in this study. All hearts underwent detailed gross and histological examination. Circumstances of death, medical history, and post-mortem pathological findings were thoroughly  investigated. Out of 535 cases of sudden cardiac death, there were 22 cases (4.1% diagnosed as having cardiomyopathies; sudden death was their first presentation. Eighteen cases (81.8% were male, with the 4th decade (11 cases, 50% being the most affected age; severe physical activity and exertion were evident in death circumstances of 14 cases (63.6%; pathological evaluation revealed that hypertrophic cardiomyopathy was the most frequent type, being diagnosed in 10 cases (45%. Cardiomyopathies are an infrequent cause of sudden cardiac death. Most deaths are in children and adults, so cases are of high social impact that demands multidisciplinary research and resources. In all cases of SCD, forensic autopsy should be done. Forensic study is the key to identifying an affected family and the starting point regarding assessing them.

  5. Manual hyperinflation partly prevents reductions of functional residual capacity in cardiac surgical patients--a randomized controlled trial

    NARCIS (Netherlands)

    Paulus, Frederique; Veelo, Denise P.; de Nijs, Selma B.; Beenen, Ludo F. M.; Bresser, Paul; de Mol, Bas A. J. M.; Binnekade, Jan M.; Schultz, Marcus J.

    2011-01-01

    Cardiac surgery is associated with post-operative reductions of functional residual capacity (FRC). Manual hyperinflation (MH) aims to prevent airway plugging, and as such could prevent the reduction of FRC after surgery. The main purpose of this study was to determine the effect of MH on

  6. Effect of Thymol on Serum Antioxidant Capacity of Rats Following Myocardial Hypertrophy

    Directory of Open Access Journals (Sweden)

    Mohabbat Jamhiri

    2017-07-01

    Full Text Available Abstract Background: Oxidative stress plays an important role in the pathogenesis of hypertension- induced cardiac hypertrophy. Plants are a rich source of antioxidant compounds. Thymol is a natural monoterpen phenol which is plentiful in some plants and shows many biological effects. The aim of the present study was to assess the effects of thymol on activity of antioxidant enzyme catalase, malondialdehyde (MDA level and the activity of the inhibition of free radical DPPH (2,2-Diphenyl-1-picryl-hydrazyl, following left ventricular hypertrophy in rats. Materials and Methods: In this experimental study, rats were divided into hypertrophied group without any treatment (H group and rats pretreated with 25 and 50 mg/kg/day of thymol (Thy25+H and Thy50+H groups, respectively. Intact animals were served as control (Ctl. Animal model of left ventricular hypertrophy was induced by abdominal aortic banding. Serum catalase (CAT activity, malondialdehyde (MDA level and the activity of inhibition of free radicals DPPH were determined by the biochemical methods. Results: In Thy25+H and Thy50+H groups, the CAT activity was increased significantly in serum (p<0.01, vs. Ctl. Also, serum level of MDA was decreased significantly compared to the group H in Thy25+H and Thy50+H groups (p<0.05 and p<0.001, respectively. The effect of inhibiting DPPH free radicals was increased significantly in Thy25+H and Thy50+H groups compared to the group H (p<0.001 and p<0.05, respectively. Conclusion: The findings of this study suggest that thymol as an antioxidant causes cardioprotective effects and as well as prevents left ventricular hypertrophy via augmentation of serum antioxidant capacity.

  7. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  8. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    International Nuclear Information System (INIS)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

    2009-01-01

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal α-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  9. PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.

    Science.gov (United States)

    Huelsmann, Martin; Neuhold, Stephanie; Resl, Michael; Strunk, Guido; Brath, Helmut; Francesconi, Claudia; Adlbrecht, Christopher; Prager, Rudolf; Luger, Anton; Pacher, Richard; Clodi, Martin

    2013-10-08

    The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP). Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context. A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years. At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

    Science.gov (United States)

    Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

    2016-01-01

    Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

  11. Carvedilol for prevention of atrial fibrillation after cardiac surgery: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hui-Shan Wang

    Full Text Available BACKGROUND: Postoperative atrial fibrillation (POAF remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF. OBJECTIVE: To investigate the efficacy of carvedilol in preventing POAF. METHODS: PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR with 95% confidence interval (CI was calculated using random- or fixed-effect models when appropriate. Six comparative trials (three randomized controlled trials and three nonrandomized controlled trials including 765 participants met the inclusion criteria. RESULTS: Carvedilol was associated with a significant reduction in POAF (relative risk [RR] 0.49, 95% confidence interval [CI] 0.37 to 0.64, p<0.001. Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF (RR 0.51, 95% CI 0.37 to 0.70, p<0.001. No evidence of heterogeneity was observed. CONCLUSIONS: In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF.

  12. Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

    NARCIS (Netherlands)

    van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

    2013-01-01

    Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

  13. Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

    Institute of Scientific and Technical Information of China (English)

    LIU Tong; DONG Jian-zeng; GAO Yun; GAO Yu-long; CHENG Yu-tong; WANG Su; LI Zhi-zhong; ZHANG Hai-bo; MENG Xu; MA Chang-sheng

    2012-01-01

    Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients.We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus.Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

  14. Hypertension and cardiac arrhythmias

    DEFF Research Database (Denmark)

    Lip, Gregory Y.H.; Coca, Antonio; Kahan, Thomas

    2017-01-01

    Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both...... supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia......, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society...

  15. Role of heterotrimeric G protein and calcium in cardiomyocyte hypertrophy induced by IGF-1.

    Science.gov (United States)

    Carrasco, Loreto; Cea, Paola; Rocco, Paola; Peña-Oyarzún, Daniel; Rivera-Mejias, Pablo; Sotomayor-Flores, Cristian; Quiroga, Clara; Criollo, Alfredo; Ibarra, Cristian; Chiong, Mario; Lavandero, Sergio

    2014-04-01

    In the heart, insulin-like growth factor-1 (IGF-1) is a peptide with pro-hypertrophic and anti-apoptotic actions. The pro-hypertrophic properties of IGF-1 have been attributed to the extracellular regulated kinase (ERK) pathway. Recently, we reported that IGF-1 also increases intracellular Ca(2+) levels through a pertussis toxin (PTX)-sensitive G protein. Here we investigate whether this Ca(2+) signal is involved in IGF-1-induced cardiomyocyte hypertrophy. Our results show that the IGF-1-induced increase in Ca(2+) level is abolished by the IGF-1 receptor tyrosine kinase inhibitor AG538, PTX and the peptide inhibitor of Gβγ signaling, βARKct. Increases in the activities of Ca(2+) -dependent enzymes calcineurin, calmodulin kinase II (CaMKII), and protein kinase Cα (PKCα) were observed at 5 min after IGF-1 exposure. AG538, PTX, βARKct, and the dominant negative PKCα prevented the IGF-1-dependent phosphorylation of ERK1/2. Participation of calcineurin and CaMKII in ERK phosphorylation was discounted. IGF-1-induced cardiomyocyte hypertrophy, determined by cell size and β-myosin heavy chain (β-MHC), was prevented by AG538, PTX, βARKct, dominant negative PKCα, and the MEK1/2 inhibitor PD98059. Inhibition of calcineurin with CAIN did not abolish IGF-1-induced cardiac hypertrophy. We conclude that IGF-1 induces hypertrophy in cultured cardiomyocytes by activation of the receptor tyrosine kinase activity/βγ-subunits of a PTX-sensitive G protein/Ca(2+) /PKCα/ERK pathway without the participation of calcineurin. © 2013 Wiley Periodicals, Inc.

  16. Does Resistance Training Stimulate Cardiac Muscle Hypertrophy?

    Science.gov (United States)

    Bloomer, Richard J.

    2003-01-01

    Reviews the literature on the left ventricular structural adaptations induced by resistance/strength exercise, focusing on human work, particularly well-trained strength athletes engaged in regular, moderate- to high-intensity resistance training (RT). The article discusses both genders and examines the use of anabolic-androgenic steroids in…

  17. [Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager].

    Science.gov (United States)

    Lederbogen, F; Schwarz, P; Häfner, S; Schweiger, U; Bohus, M; Deuschle, M

    2015-07-01

    People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

  18. Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

    Directory of Open Access Journals (Sweden)

    Tulay Akman

    2014-11-01

    Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

  19. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy ...

    African Journals Online (AJOL)

    Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro. Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under ...

  20. Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

    African Journals Online (AJOL)

    Diabetes or hyperglycemia disrupts HIF-mediated cardiac hypertrophy adaptive regulatory mechanism [14]. In diabetic retinopathy, abnormal increase of ... detection system. Flow cytometry. After digesting with EDTA-free trypsin, the H9C2 cells were centrifuged at 1000 rpm for 5 min. After discarding the medium, the cells ...

  1. Multicenter Quality Improvement Project to Prevent Sternal Wound Infections in Pediatric Cardiac Surgery Patients.

    Science.gov (United States)

    Woodward, Cathy; Taylor, Richard; Son, Minnette; Taeed, Roozbeh; Jacobs, Marshall L; Kane, Lauren; Jacobs, Jeffrey P; Husain, S Adil

    2017-07-01

    Children undergoing cardiac surgery are at risk for sternal wound infections (SWIs) leading to increased morbidity and mortality. Single-center quality improvement (QI) initiatives have demonstrated decreased infection rates utilizing a bundled approach. This multicenter project was designed to assess the efficacy of a protocolized approach to decrease SWI. Pediatric cardiac programs joined a collaborative effort to prevent SWI. Programs implemented the protocol, collected compliance data, and provided data points from local clinical registries using Society of Thoracic Surgery Congenital Heart Surgery Database harvest-compliant software or from other registries. Nine programs prospectively collected compliance data on 4,198 children. Days between infections were extended from 68.2 days (range: 25-82) to 130 days (range: 43-412). Protocol compliance increased from 76.7% (first quarter) to 91.3% (final quarter). Ninety (1.9%) children developed an SWI preprotocol and 64 (1.5%) postprotocol, P = .18. The 657 (15%) delayed sternal closure patients had a 5% infection rate with 18 (5.7%) in year 1 and 14 (4.3%) in year 2 P = .43. Delayed sternal closure patients demonstrated a trend toward increased risk for SWI of 1.046 for each day the sternum remained open, P = .067. Children who received appropriately timed preop antibiotics developed less infections than those who did not, 1.9% versus 4.1%, P = .007. A multicenter QI project to reduce pediatric SWIs demonstrated an extension of days between infections and a decrease in SWIs. Patients who received preop antibiotics on time had lower SWI rates than those who did not.

  2. Evidence to service gap: cardiac rehabilitation and secondary prevention in rural and remote Western Australia.

    Science.gov (United States)

    Hamilton, Sandra; Mills, Belynda; McRae, Shelley; Thompson, Sandra

    2018-01-30

    Cardiovascular disease (CVD), a leading cause of morbidity and mortality, has similar incidence in metropolitan and rural areas but poorer cardiovascular outcomes for residents living in rural and remote Australia. Cardiac Rehabilitation (CR) is an evidence-based intervention that helps reduce subsequent cardiovascular events and rehospitalisation. Unfortunately CR attendance rates are as low as 10-30% with rural/remote populations under-represented. This in-depth assessment investigated the provision of CR and secondary prevention services in Western Australia (WA) with a focus on rural and remote populations. CR and Aboriginal Community Controlled Health Services were identified through the Directory of Western Australian Cardiac Rehabilitation and Secondary Prevention Services 2012. Structured interviews with CR coordinators included questions specific to program delivery, content, referral and attendance. Of the 38 CR services identified, 23 (61%) were located in rural (n = 11, 29%) and remote (n = 12, 32%) regions. Interviews with coordinators from 34 CR services (10 rural, 12 remote, 12 metropolitan) found 77% of rural/remote services were hospital-based, with no service providing a comprehensive home-based or alternative method of program delivery. The majority of rural (60%) and remote (80%) services provided CR through chronic condition exercise programs compared with 17% of metropolitan services; only 27% of rural/remote programs provided education classes. Rural/remote coordinators were overwhelmingly physiotherapists, and only 50% of rural and 33% of remote programs had face-to-face access to multidisciplinary support. Patient referral and attendance rates differed greatly across WA and referrals to rural/remote services generally numbered less than 5 per month. Program evaluation was reported by 33% of rural/remote coordinators. Geography, population density and service availability limits patient access to CR services in rural/remote WA. Current

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

    Directory of Open Access Journals (Sweden)

    Nikole J. Byrne, BSc

    2017-08-01

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

  4. Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

    DEFF Research Database (Denmark)

    Corrà, Ugo; Piepoli, Massimo F; Carré, François

    2010-01-01

    , exercise training, diet/nutritional counselling, weight control management, lipid management, blood pressure monitoring, smoking cessation, and psychosocial management. Cardiac rehabilitation services are by definition multi-factorial and comprehensive, with physical activity counselling and exercise...... training as central components in all rehabilitation and preventive interventions. Many of the risk factor improvements occurring in CR can be mediated through exercise training programmes. This call-for-action paper presents the key components of a CR programme: physical activity counselling and exercise...

  5. The role of satellite cells in muscle hypertrophy.

    Science.gov (United States)

    Blaauw, Bert; Reggiani, Carlo

    2014-02-01

    The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.

  6. RSK3 is required for concentric myocyte hypertrophy in an activated Raf1 model for Noonan syndrome.

    Science.gov (United States)

    Passariello, Catherine L; Martinez, Eliana C; Thakur, Hrishikesh; Cesareo, Maria; Li, Jinliang; Kapiloff, Michael S

    2016-04-01

    Noonan syndrome (NS) is a congenital disorder resulting from mutations of the Ras-Raf signaling pathway. Hypertrophic cardiomyopathy associated with RAF1 "RASopathy" mutations is a major risk factor for heart failure and death in NS and has been attributed to activation of MEK1/2-ERK1/2 mitogen-activated protein kinases. We recently discovered that type 3 p90 ribosomal S6 kinase (RSK3) is an ERK effector that is required, like ERK1/2, for concentric myocyte hypertrophy in response to pathological stress such as pressure overload. In order to test whether RSK3 also contributes to NS-associated hypertrophic cardiomyopathy, RSK3 knock-out mice were crossed with mice bearing the Raf1(L613V) human NS mutation. We confirmed that Raf1(L613V) knock-in confers a NS-like phenotype, including cardiac hypertrophy. Active RSK3 was increased in Raf1(L613V) mice. Constitutive RSK3 gene deletion prevented the Raf1(L613V)-dependent concentric growth in width of the cardiac myocyte and attenuated cardiac hypertrophy in female mice. These results are consistent with RSK3 being an important mediator of ERK1/2-dependent growth in RASopathy. In conjunction with previously published data showing that RSK3 is important for pathological remodeling of the heart, these data suggest that targeting of this downstream MAP-kinase pathway effector should be considered in the treatment of RASopathy-associated hypertrophic cardiomyopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Idiopathic masseter muscle hypertrophy.

    Science.gov (United States)

    Kebede, Biruktawit; Megersa, Shimalis

    2011-11-01

    Benign Masseteric Hypertrophy is a relatively uncommon condition that can occur unilaterally or bilaterally. Pain may be a symptom, but most frequently a clinician is consulted for cosmetic reasons. In some cases prominent Exostoses at the angle of the mandible are noted. Although it is tempting to point to Malocclusion, Bruxism, clenching, or Temporomandibular joint disorders, the etiology in the majority of cases is unclear. Diagnosis is based on awareness of the condition, clinical and radiographic findings, and exclusion of more serious Pathology such as Benign and Malignant Parotid Disease, Rhabdomyoma, and Lymphangioma. Treatment usually involves resection of a portion of the Masseter muscle with or without the underlying bone.

  8. The role of long-term antibiotics in the prevention of infection in postoperative cardiac surgeries

    International Nuclear Information System (INIS)

    Shahid, U.; Arain, M.A.; Dar, M.I.; Khan, A.B.; Aftab, S.; Manan, A.U.

    2007-01-01

    To compare the effect of long-term (7 days) versus short-term (2 days) postoperative antibiotics in preventing postoperative infective complications in patients who have undergone open-heart surgeries. Cardiac patients (n=42), operated for valvular disease (36%), coronary artery bypass grafting (50%), or septal repair (14%), were included in our study. Patients were prospectively randomized into two groups. Group A (n=21) patients received oral antibiotics for 7 days, whereas group B (n=21) patients were given the same for 2 days postoperative. Pre-operative and intraoperative variables were equal in both groups. Total leukocyte count and temperature were monitored daily until the patients were discharged. The chest and leg wounds were inspected daily for any signs of infection. Sputum and urine cultures were sent for selected patients in case of respiratory tract infection or urinary tract infection, respectively. Each patient was followed until the next routine visit in outpatient department. In group A, 3 patients (14%), developed infection postoperatively, whereas in group B, 13 patients (62%) (p =0.001) had to be started on oral or intravenous antibiotics as a result of developing either wound infection, a positive sputum culture, a positive urine culture or a localized infection elsewhere. Mean ward stay in group A was 4.8 +- 4.5 days and in group B 6.5 +- 4.1 days (p =0.011). In this series, there was a significantly higher frequency of infection and longer hospital stay in patients who received antibiotics for 2 days postoperatively as compared to those who received antibiotics for 7 days. (author)

  9. Tissue characteristics in left ventricular hypertrophy using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Yoshida, Shigeru; Ueno, Yuji; Arita, Mikio; Nishio, Ichiro; Masuyama, Yoshiaki

    1988-01-01

    For 15 normotensive patients with asymmetric septal hypertrophy (ASH), 10 hypertensive patients with concentric hypertrophy (CH), and five normal subjects (N), we examined changes in myocardial T 1 and T 2 values related to the cardiac cycle. The usefulness of those values in differentiating diseases with left ventricular hypertrophy was evaluated. Left ventricular (LV) short-axis spin echo images and inversion recovery images were obtained at endsystolic and diastolic cardiac phases, and T 1 and T 2 images were calculated. The regional wall thickness (WT) and T 1 and T 2 values were measured in the anterior septum, anterior wall, lateral wall, posterior wall and posterior septum. Myocardial T 1 and T 2 values were significantly decreased in systole (T 1 : 185.6±37.9 msec, T 2 : 24.4±6.3 msec, mean±SD) compared to those in diastole (T 1 : 249.2±56.7 msec, T 2 : 31.7±9.4 msec). In both the ASH and CH groups, significant correlations were observed between diastolic T 1 values and WT (ASH: r = 0.80, p 2 values and WT (ASH: r = 0.58, p 1 values in the ASH group (343.4±40.5 msec) were significantly higher than those of the CH group (247.3±21.4 msec), although the mean wall thickness values were similar in both groups. The T 1 /WT and T 2 /WT were significantly lower in the CH group than those in the ASH and N groups. In conclusion, myocardial T 1 and T 2 values were related not only to the cardiac cycle, but to wall thickness and to types of hypertrophy. The T 1 and T 2 values may be useful for distinguishing hypertrophic cardiomyopathy from hypertrophy due to hypertension. (author)

  10. Wound ventilation : A new concept for prevention of complications in cardiac surgery

    OpenAIRE

    Persson, Mikael

    2003-01-01

    Cardiac surgery through an open chest wound is a major operation both in size and duration. The wound exposure to ambient air implies considerable risks. 1) Air may enter the heart and great vessels and embolize to the brain or cardiac muscle where it may cause dysfunction or permanent damage. 2) The wound is exposed to airborne bacterial contamination, which may lead to postoperative wound infection. 3) The wound is subjected to desiccation, which may lead to serious adhesi...

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

    Science.gov (United States)

    Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

    2016-01-15

    Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Prevention of liver cancer cachexia-induced cardiac wasting and heart failure

    Science.gov (United States)

    Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Mareike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J.S.; Beadle, John; Argiles, Josep M.; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D.

    2014-01-01

    Aims Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Methods and results Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Conclusion Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer. PMID:23990596

  14. Pregnancy as a cardiac stress model

    Science.gov (United States)

    Chung, Eunhee; Leinwand, Leslie A.

    2014-01-01

    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

  15. Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

    Science.gov (United States)

    Myerburg, Robert J; Ullmann, Steven G

    2015-04-01

    Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise. © 2015 American Heart Association, Inc.

  16. PREVENTION OF LEFT VENTRICLE SYSTOLIC DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST SEGMENT ELEVATION AFTER CARDIAC REVASCULARIZATION

    Directory of Open Access Journals (Sweden)

    A. L. Alyavi

    2016-01-01

    Full Text Available Aim. To study effects of bioflavonoid quercetin (corvitin on left ventricle (LV systolic dysfunction in patients with acute coronary syndrome with ST segment elevation (ACS+ST after cardiac revascularization.Material and methods. 60 patients with ACS+ST (44,2±1,3 y.o. were examined. Patients were admitted to hospital within 6 hours after complaints beginning. Patients were randomized in two groups. 30 patients of group A had standard therapy and cardiac revascularization. 30 patients of group B received corvitin additionally to standard therapy before cardiac revascularization. Echocardiography initially and stress-echocardiography with dobutamine after status stabilization (at 8-10 days of disease were performed.Results. Dobutamine test (with low and high doses showed myocardial viability in patients of group B. Patients of group A had irreversible LV systolic dysfunction in 32 % of segments. Corvitin slowed down LV dilatation progression in patients with ACS+ST. It resulted in the end-diastolic and end-systolic indexes did not change within 10 days. The LV ejection fraction was more increased in patients of group B in comparison with patients of group A.Conclusion. The early corvitin prescribing has positive effects on LV systolic function and prevents post-reperfusion complications. 

  17. PREVENTION OF LEFT VENTRICLE SYSTOLIC DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST SEGMENT ELEVATION AFTER CARDIAC REVASCULARIZATION

    Directory of Open Access Journals (Sweden)

    A. L. Alyavi

    2009-01-01

    Full Text Available Aim. To study effects of bioflavonoid quercetin (corvitin on left ventricle (LV systolic dysfunction in patients with acute coronary syndrome with ST segment elevation (ACS+ST after cardiac revascularization.Material and methods. 60 patients with ACS+ST (44,2±1,3 y.o. were examined. Patients were admitted to hospital within 6 hours after complaints beginning. Patients were randomized in two groups. 30 patients of group A had standard therapy and cardiac revascularization. 30 patients of group B received corvitin additionally to standard therapy before cardiac revascularization. Echocardiography initially and stress-echocardiography with dobutamine after status stabilization (at 8-10 days of disease were performed.Results. Dobutamine test (with low and high doses showed myocardial viability in patients of group B. Patients of group A had irreversible LV systolic dysfunction in 32 % of segments. Corvitin slowed down LV dilatation progression in patients with ACS+ST. It resulted in the end-diastolic and end-systolic indexes did not change within 10 days. The LV ejection fraction was more increased in patients of group B in comparison with patients of group A.Conclusion. The early corvitin prescribing has positive effects on LV systolic function and prevents post-reperfusion complications. 

  18. Dexamethasone for the prevention of postpericardiotomy syndrome: A DExamethasone for Cardiac Surgery substudy

    NARCIS (Netherlands)

    Bunge, Jeroen J. H.; van Osch, Dirk; Dieleman, Jan M.; Jacob, Kirolos A.; Kluin, Jolanda; van Dijk, Diederik; Nathoe, Hendrik M.; Bredée, Jaap J.; Buhre, Wolfgang F.; van Herwerden, Lex A.; Kalkman, Cor J.; van Klarenbosch, Jan; Moons, Karel G.; Numan, Sandra C.; Ottens, Thomas H.; Roes, Kit C.; Sauer, Anne-Mette C.; Slooter, Arjen J.; Nierich, Arno P.; Ennema, Jacob J.; Rosseel, Peter M.; van der Meer, Nardo J.; van der Maaten, Joost M.; Cernak, Vlado; Hofland, Jan; van Thiel, Robert J.; Diephuis, Jan C.; Schepp, Ronald M.; Haenen, Jo; de Lange, Fellery; Boer, Christa; de Jong, Jan R.; Tijssen, Jan G.

    2014-01-01

    The postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery. The pathophysiology remains unclear, although evidence exists that surgical trauma and the use of cardiopulmonary bypass provoke an immune response leading to PPS. We hypothesized that an intraoperative dose of

  19. Syncope and the risk of sudden cardiac death: Evaluation, management, and prevention

    Directory of Open Access Journals (Sweden)

    Ryan J. Koene, MD

    2017-12-01

    Full Text Available Syncope is a clinical syndrome defined as a relatively brief self-limited transient loss of consciousness (TLOC caused by a period of inadequate cerebral nutrient flow. Most often the trigger is an abrupt drop of systemic blood pressure. True syncope must be distinguished from other common non-syncope conditions in which real or apparent TLOC may occur such as seizures, concussions, or accidental falls. The causes of syncope are diverse, but in most instances, are relatively benign (e.g., reflex and orthostatic faints with the main risks being accidents and/or injury. However, in some instances, syncope may be due to more worrisome conditions (particularly those associated with cardiac structural disease or channelopathies; in such circumstances, syncope may be an indicator of increased morbidity and mortality risk, including sudden cardiac death (SCD. Establishing an accurate basis for the etiology of syncope is crucial in order to initiate effective therapy. In this review, we focus primarily on the causes of syncope that are associated with increased SCD risk (i.e., sudden arrhythmic cardiac death, and the management of these patients. In addition, we discuss the limitations of our understanding of SCD in relation to syncope, and propose future studies that may ultimately address how to improve outcomes of syncope patients and reduce SCD risk. Keywords: Syncope, Sudden cardiac death, Risk assessment

  20. Compensative hypertrophy of the kidney

    International Nuclear Information System (INIS)

    Raynaud, C.

    1976-01-01

    Several measurement methods are available to practitioners to reveal a compensative hypertrophy. Mensuration of the kidney has the advantage of simplicity but is in fact an unreliable and inaccurate method. Separate clearances in their traditional form have never entered into routine use because of the disadvantages of ureteral catheterism. The use of radioactive tracers avoids this drawback, but clearances calculated in this way are only valid in the absence of obstructive urinary disorders. Solutions have been proposed, but the values obtained are no longer identical with the clearances. The Hg uptake test quantifies quite accurately the function of each kidney. From the results obtained a complete compensative hypertrophy developed on a healthy kidney and an incomplete compensative hypertrophy developed on the diseased kidney have been described. In each of these situations the degree to which compensative hypertrophy develops seems to be fixed at a given level peculiar to each patient [fr

  1. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

    Directory of Open Access Journals (Sweden)

    Takanobu Nagata

    Full Text Available Myocardial ischemia reperfusion injury (IRI adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS-3, an intrinsic negative feedback regulator of the Janus kinase (JAK-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO. The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1 was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

  2. Comprehensive cardiac rehabilitation for secondary prevention after transient ischemic attack or mild stroke: I: feasibility and risk factors.

    Science.gov (United States)

    Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville

    2011-11-01

    Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; Pstroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

  3. Prevention of sudden cardiac death in athletes, sportspersons and marathoners in India

    Directory of Open Access Journals (Sweden)

    Amit Vora

    2018-01-01

    Full Text Available The annual incidence of sudden cardiac death (SCD in athletes is significantly lower than the general population. However, when SCD occurs in an athlete during sporting event or training, it sends shockwaves in the society and raises questions about cardiovascular effects of sports and exercise. This document reviews the causes and mechanism of SCD in sports and exercise in young and older athletes. In the Indian context, we suggest a ‘pre-participation screening’ of young and older athletes and consider a ‘supervised, graded exercise regime’ for the uninitiated, older sports participant. Finally, the document proposes medical infrastructure required to successfully revive a victim of sudden cardiac arrest during a sporting event.

  4. Epidermal growth factor inhibits rat pancreatic cell proliferation, causes acinar cell hypertrophy, and prevents caerulein-induced desensitization of amylase release.

    Science.gov (United States)

    Morisset, J; Larose, L; Korc, M

    1989-06-01

    The in vivo effects of epidermal growth factor (EGF) on pancreatic growth and digestive enzyme concentrations were compared with the actions of the pancreatic secretagogue caerulein in the adult rat. EGF (10 micrograms/kg BW) did not alter pancreatic weight or protein content. However, this concentration of EGF inhibited [3H]thymidine incorporation into DNA by 44%, decreased DNA content by 20%, and increased the concentrations of amylase, chymotrypsinogen, and protein by 106%, 232%, and 42%, respectively. Pancreatic acini prepared from EGF-treated rats exhibited a characteristic secretory response to caerulein that was superimposable to that obtained in acini from saline-treated rats. In both groups of acini half-maximal and maximal stimulation of amylase release occurred at approximately 5 pM and 50 pM caerulein, respectively. In contrast to EGF, caerulein (1 microgram/kg BW) increased pancreatic weight by 29% and protein content by 59%, and enhanced [3H]thymidine incorporation into DNA by 70%. Although caerulein increased the concentrations of pancreatic amylase and chymotrypsinogen by 38% and 297%, respectively, pancreatic acini prepared from caerulein-treated rats were less sensitive to the actions of caerulein in vitro when compared with acini from control rats. Indeed, the EC50 was shift from 4.8 pM to 9.8 pM after 4 days of treatment. EGF potentiated the actions of caerulein on pancreatic weight, protein content, and chymotrypsinogen concentration, and prevented the caerulein-induced alteration in the secretory responsiveness of the acinar cell. Conversely, caerulein reversed the inhibitory effect of EGF on thymidine incorporation. These findings suggest that EGF may modulate the trophic effects of certain gastrointestinal hormones, and may participate in the regulation of pancreatic exocrine function in vivo.

  5. Preventing Sudden Cardiac Death: Automated External Defibrillators in Ohio High Schools.

    Science.gov (United States)

    Lear, Aaron; Hoang, Minh-Ha; Zyzanski, Stephen J

    2015-10-01

    Ohio passed legislation in 2004 for optional public funding of automated external defibrillators (AEDs) in all Ohio high schools. To report occurrences of sudden cardiac arrest in which AEDs were used in Ohio high schools and to evaluate the adherence of Ohio high schools with AEDs to state law and published guidelines on AEDs and emergency action plans (EAPs) in schools. Cross-sectional survey. Web-based survey. A total of 264 of 827 schools that were members of the Ohio High School Athletic Association. We surveyed schools on AED use, AED maintenance, and EAPs. Twenty-five episodes of AED deployment at 22 schools over an 11-year period were reported; 8 (32%) involved students and 17 (68%) involved adults. The reported survival rate was 60% (n = 15). Most events (n = 20, 80%) in both students and adults occurred at or near athletic facilities. The annual use rate of AEDs was 0.7%. Fifty-three percent (n = 140) of schools reported having an EAP in place for episodes of cardiac arrest. Of the schools with EAPs, 57% (n = 80) reported having rehearsed them. Our data supported the placement of AEDs in high schools given the frequency of use for sudden cardiac arrest and the survival rate reported. They also suggested the need for increased awareness of recommendations for EAPs and the need to formulate and practice EAPs. School EAPs should emphasize planning for events in the vicinity of athletic facilities.

  6. The effect of 12 weeks of aerobic exercise on plasma levels of fibroblast growth factor 23, Angiotensin converting enzyme and left ventricular hypertrophy in hypertensive elderly women

    Directory of Open Access Journals (Sweden)

    Z Keshavarzi

    2017-06-01

    Conclusion: The results of this study demonstrated that aerobic exercise has a positive effect on heart function and serum levels of ACE, and can potentially reverse cardiac dysfunction associated with left ventricular hypertrophy.

  7. Prolactin induces adrenal hypertrophy

    Directory of Open Access Journals (Sweden)

    E.J. Silva

    2004-02-01

    Full Text Available Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc. In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05, and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05. We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05, and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05. Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

  8. Cardiac effects of noncardiac neoplasms

    International Nuclear Information System (INIS)

    Schoen, F.J.; Berger, B.M.; Guerina, N.G.

    1984-01-01

    Clinically significant cardiovascular abnormalities may occur as secondary manifestations of noncardiac neoplasms. The principal cardiac effects of noncardiac tumors include the direct results of metastases to the heart or lungs, the indirect effects of circulating tumor products (causing nonbacterial thrombotic endocarditis, myeloma-associated amyloidosis, pheochromocytoma-associated cardiac hypertrophy and myofibrillar degeneration, and carcinoid heart disease), and the undesired cardiotoxicities of chemotherapy and radiotherapy. 89 references

  9. Possibly preventable cardiac arrest in a morbidly obese patient - a comment on the 2015 ERC guidelines.

    Science.gov (United States)

    Hans, Felix Patricius; Hoeren, Claudia Johanna Maria; Kellmeyer, Phillipp; Hohloch, Lisa; Busch, Hans-Jörg; Bayer, Jörg

    2016-10-04

    The incidence of overweight and obesity has been steadily on the rise and has reached epidemic proportions in various countries and this represents a well-known major health problem. Nevertheless, current guidelines for resuscitation do not include special sequences of action in this subset of patients. The aim of this letter is to bring this controversy into focus and to suggest alterations of the known standard cardiopulmonary resuscitation in the obese. An obese patient weighing 272 kg fell to the floor, afterwards being unable to get up again. Thus, emergency services were called for assistance. There were no signs or symptoms signifying that the person had been harmed in consequence of the fall. Only when brought into a supine position the patient suffered an immediate cardiac arrest. Cardiopulmonary resuscitation was performed but there was no return of a stable spontaneous circulation until the patient was brought into a full lateral position. In spite of immediate emergency care the patient ultimately suffered a lethal hypoxic brain damage. A full lateral position should be considered in obese patients having a cardiac arrest as it might help to re-establish stable circulatory conditions.

  10. Role of cardiac magnetic resonance imaging focusing on QOL and preventive medicine

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Ito, Hirotoshi; Kubota, Takao

    2003-01-01

    Cardiac magnetic resonance imaging (MRI) using fast imaging techniques has been developing quickly recently. Left ventricular function with pharmacological intervention can be evaluated using True fast imaging with steady-state precession (FISP) method. In addition, left ventricular diastolic function can be evaluated by retrospective gating with a high frame rate. Myocardial perfusion and viability can also be evaluated by first-pass imaging and delayed enhancement with Gd-DTPA. Data concerning myocardial ischemia, viability, and left ventricular function is now almost equivalent to that of myocardial SPECT and contrast echo. Additionally, coronary arterial narrowing and coronary vessel wall can be visualized with both the bright-blood and black-blood method. These methods are still currently in the research stage. The prognostic value of myocardial perfusion and ventricular function in ischemic heart disease should be established using large numbers of patients. Multi-center trials using cardiac MRI should be recommended for this purpose. Furthermore, detecting acute coronary syndrome in the emergency department can be performed with safety and accuracy. MR coronary angiography should be used not only for flow-limiting coronary stenosis but also the atherosclerotic wall region. This provides information that may predict cardiovascular risk, and facilitate further study of artherothrombosis, progression and response to therapy. It may also provide for the assessment of subclinical disease. (author)

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

    Science.gov (United States)

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

    2012-01-01

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

  12. Can sudden cardiac death in the young be predicted and prevented? Lessons from autopsy for the emergency physician.

    Science.gov (United States)

    White, Jennifer L; Chang, Anna Marie; Cesar, Sergi; Sarquella-Brugada, Georgia

    2018-06-01

    Sudden unexpected death in the young, though rare, is devastating for both the family and the community. Although only 1.3 to 8.5 cases of sudden cardiac death (SCD) occur per 100 000 young people, autopsy is often inconclusive. Many causes of SCD are related to autosomal dominant inherited risk, however; therefore, answers are important for survivors. Causes of autopsy-positive SCD in young patients include hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia. Autopsy-negative SCD has been related to inherited arrhythmogenic causes such as long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, Wolff- Parkinson-White syndrome, and idiopathic ventricular fibrillation. The important question for the emergency physician is how SCD can be predicted and prevented in the young so that there is no need for an autopsy.

  13. Dosing of Milrinone in Preterm Neonates to Prevent Postligation Cardiac Syndrome: Simulation Study Suggests Need for Bolus Infusion.

    Science.gov (United States)

    Hallik, Maarja; Tasa, Tõnis; Starkopf, Joel; Metsvaht, Tuuli

    2017-01-01

    Milrinone has been suggested as a possible first-line therapy for preterm neonates to prevent postligation cardiac syndrome (PLCS) through decreasing systemic vascular resistance and increasing cardiac contractility. The optimal dosing regimen, however, is not known. To model the dosing of milrinone in preterm infants for prevention of PLCS after surgical closure of patent ductus arteriosus (PDA). Milrinone time-concentration profiles were simulated for 1,000 subjects using the volume of distribution and clearance estimates based on one compartmental population pharmacokinetic model by Paradisis et al. [Arch Dis Child Fetal Neonatal Ed 2007;92:F204-F209]. Dose optimization was based on retrospectively collected demographic data from neonates undergoing PDA ligation in Estonian PICUs between 2012 and 2014 and existing pharmacodynamic data. The target plasma concentration was set at 150-200 ng/ml. The simulation study used demographic data from 31 neonates who underwent PDA ligation. The median postnatal age was 13 days (range: 3-29) and weight was 760 g (range: 500-2,351). With continuous infusion of milrinone 0.33 μg/kg/min, the proportion of subjects within the desired concentration range was 0% by 3 h, 36% by 6 h, and 61% by 8 h; 99% of subjects exceeded the range by 18 h. The maximum proportion of total simulated concentrations in the target range was attained with a bolus infusion of 0.73 μg/kg/min for 3 h followed by a 0.16-μg/kg/min maintenance infusion. Mathematical simulations suggest that in preterm neonates the plasma time-concentration profile of milrinone can be optimized with a slow loading dose followed by maintenance infusion. © 2016 S. Karger AG, Basel.

  14. Discrete event simulation model of sudden cardiac death predicts high impact of preventive interventions.

    Science.gov (United States)

    Andreev, Victor P; Head, Trajen; Johnson, Neil; Deo, Sapna K; Daunert, Sylvia; Goldschmidt-Clermont, Pascal J

    2013-01-01

    Sudden Cardiac Death (SCD) is responsible for at least 180,000 deaths a year and incurs an average cost of $286 billion annually in the United States alone. Herein, we present a novel discrete event simulation model of SCD, which quantifies the chains of events associated with the formation, growth, and rupture of atheroma plaques, and the subsequent formation of clots, thrombosis and on-set of arrhythmias within a population. The predictions generated by the model are in good agreement both with results obtained from pathological examinations on the frequencies of three major types of atheroma, and with epidemiological data on the prevalence and risk of SCD. These model predictions allow for identification of interventions and importantly for the optimal time of intervention leading to high potential impact on SCD risk reduction (up to 8-fold reduction in the number of SCDs in the population) as well as the increase in life expectancy.

  15. Comparison of granisetron, metoclopramide and gastric decompression for prevention of postoperative nausea and vomiting after fast track cardiac anesthesia

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    Omid Aghadavoudi

    2008-08-01

    Full Text Available

    • BACKGROUND: Different methods have been suggested to prevent postoperative nausea and vomiting (PONV, but the efficacy of these methods has not been fully studied in fast track cardiac anesthesia (FTCA.
    • METHODS: In a randomized double blind clinical trial study, 120 patients aged 18-70 years with ASA II or III, undergoing elective cardiac surgery, were selected. They were divided randomly into four groups. In group M, group G and group P, intravenous (IV metoclopramide (0.1 mg/kg, granisetron (0.01 mg/kg, and normal saline were administered, respectively, about thirty minutes before extubation in the intensive care unit (ICU. In group N, a nasogastric (NG tube was inserted after tracheal intubation in the operating room and removed about thirty minutes before extubation in the ICU. The incidence and severity of nausea and the episodes of vomiting were recorded by a blinded investigator at the time of extubation and performed regularly for a maximum of 24 hours. Assessment of severity of nausea was scored using a visual analogue scale (VAS device. Data were analyzed by using ANOVA, chi-squared and Kruskal- Wallis and repeated measures tests.
    • RESULTS: Overall the 24-h incidence of PONV was significantly lower in the G and M groups than in the P and N groups (10% and 16.7% vs. 33.3% and 40%, respectively; P < 0.02. Postoperative rescue medication was significantly less required in the G and M groups compared to the other two groups (P < 0.01. Less satisfaction, according to PONV status, was observed in the P and N groups (P < 0.01.
    • CONCLUSIONS: According to this study, metoclopramide and granisetron, but not gastric decompression, are effective regimens for preventing PONV after FTCA. Given the economics and a considerable background incidence in patients exhibiting PONV, we suggest metoclopramide as a routine prophylactic antiemetic in FTCA

    • Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

      Science.gov (United States)

      Ianuzzo, C. D.; Chen, V.

      1977-01-01

      Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

    • Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

      Directory of Open Access Journals (Sweden)

      Jie Wu

      Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

    • Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study.

      Science.gov (United States)

      Caru, Maxime; Kern, Laurence; Bousquet, Marc; Curnier, Daniel

      2018-04-26

      To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs). A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors ( i.e ., abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking). It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression. This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce a protection for some risk factors, despite having a CVD.

    • Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis.

      Science.gov (United States)

      Khangura, Jaspreet; Culleton, Bruce F; Manns, Braden J; Zhang, Jianguo; Barnieh, Lianne; Walsh, Michael; Klarenbach, Scott W; Tonelli, Marcello; Sarna, Magdalena; Hemmelgarn, Brenda R

      2010-06-24

      Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC). Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy. A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

    • Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis

      Directory of Open Access Journals (Sweden)

      Walsh Michael

      2010-06-01

      Full Text Available Abstract Background Left ventricular (LV hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. Methods This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra-dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month. Agreement was assessed using Lin's concordance correlation coefficient (CCC and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC. Results Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre-dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80 predictive power for LV hypertrophy. Conclusions A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results.

  1. Analysis of Pre-participation Screening Protocols for Football Players in Europe, USA, and Libya: Possible Implications for Preventing Sudden Cardiac Death

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    Salaheddin Sharif

    2017-06-01

    Full Text Available Sudden cardiac death is the leading cause of death in sport participants and may result from undiagnosed cardiac diseases. It has been universally agreed upon that pre-participation screening can identify those athletes at risk of sudden cardiac death, and yet, there is no commonly accepted protocol to screen athletes. Although the European Society of Cardiology (ESC and the American Heart Association (AHA recommend the routine screening of athletes to prevent sudden death, there is significant disagreement regarding the guidelines of the protocols. The American Heart Association protocol includes a detailed medical history and a physical examination, whereas the European Society of Cardiology protocol includes 12-lead electrocardiography with a detailed medical history and a physical examination. The cost benefit of using electrocardiography is debatable, particularly if the screening is used to prevent sudden death associated with uncommon diseases. The Libyan Football Federation established a new seasonal pre-competition medical assessment protocol for Libyan football athletes during the 2013-2014 season, which includes a medical history, physical examination, 12 lead electrocardiography, echocardiography, and blood test. Regardless of cost and differences in protocol, there is a significant value in pre-participation screening for athletes in order to decrease the incidence of sudden cardiac death, and this report examines some of these different protocols as well as their potential for identifying athletes at risk for sudden cardiac death.

  2. What Does It Cost to Prevent On-Duty Firefighter Cardiac Events? A Content Valid Method for Calculating Costs

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    P. Daniel Patterson

    2013-01-01

    Full Text Available Cardiac arrest is a leading cause of mortality among firefighters. We sought to develop a valid method for determining the costs of a workplace prevention program for firefighters. In 2012, we developed a draft framework using human resource accounting and in-depth interviews with experts in the firefighting and insurance industries. The interviews produced a draft cost model with 6 components and 26 subcomponents. In 2013, we randomly sampled 100 fire chiefs out of >7,400 affiliated with the International Association of Fire Chiefs. We used the Content Validity Index (CVI to identify the content valid components of the draft cost model. This was accomplished by having fire chiefs rate the relevancy of cost components using a 4-point Likert scale (highly relevant to not relevant. We received complete survey data from 65 fire chiefs (65% response rate. We retained 5 components and 21 subcomponents based on CVI scores ≥0.70. The five main components include, (1 investment costs, (2 orientation and training costs, (3 medical and pharmaceutical costs, (4 education and continuing education costs, and (5 maintenance costs. Data from a diverse sample of fire chiefs has produced a content valid method for calculating the cost of a prevention program among firefighters.

  3. Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose.

    Science.gov (United States)

    Frantz, Stefan; Calvillo, Laura; Tillmanns, Jochen; Elbing, Inka; Dienesch, Charlotte; Bischoff, Hilmar; Ertl, Georg; Bauersachs, Johann

    2005-04-01

    Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

  4. Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest: a health technology assessment and patient focus group study

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    Ettinger S

    2017-11-01

    Full Text Available Sabine Ettinger,1 Michal Stanak,1 Piotr Szymański,2 Claudia Wild,1 Romana Tandara Haček,3 Darija Erčević,3 Renata Grenković,3 Mirjana Huić3 1Ludwig Boltzmann Institute for Health Technology Assessment, Vienna, Austria; 2Institute of Cardiology, Warsaw, Poland; 3Department for Development, Research and Health Technology Assessment, Agency for Quality and Accreditation in Health Care and Social Welfare, Zagreb, Croatia Aim: To summarize the evidence on clinical effectiveness and safety of wearable cardioverter defibrillator (WCD therapy for primary and secondary prevention of sudden cardiac arrest in patients at risk. Methods: We performed a systematic literature search in databases including MEDLINE via OVID, Embase, the Cochrane Library, and CRD (DARE, NHS-EED, HTA. The evidence obtained was summarized according to GRADE methodology. A health technology assessment (HTA was conducted using the HTA Core Model® for rapid relative effectiveness assessment. Primary outcomes for the clinical effectiveness domain were all-cause and disease-specific mortality. Outcomes for the safety domain were adverse events (AEs and serious adverse events (SAEs. A focus group with cardiac disease patients was conducted to evaluate ethical, organizational, patient, social, and legal aspects of the WCD use. Results: No randomized- or non-randomized controlled trials were identified. Non-comparative studies (n=5 reported AEs including skin rash/itching (6%, false alarms (14%, and palpitations/light-headedness/fainting (9% and discontinuation due to comfort/lifestyle issues (16–22%, and SAEs including inappropriate shocks (0–2%, unsuccessful shocks (0–0.7%, and death (0–0.3%. The focus group results reported that experiencing a sense of security is crucial to patients and that the WCD is not considered an option for weeks or even months due to expected restrictions in living a “normal” life. Conclusion: The WCD appears to be relatively safe for short

  5. Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.

    Science.gov (United States)

    Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel

    2018-06-01

    The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  6. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

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    Valentina Sala

    2016-01-01

    Full Text Available Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  7. The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi

    1999-01-01

    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123 I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting 201 Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced 201 Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

  8. Cardiac chambers and their walls in cardiomyopathies as evaluated with CT

    International Nuclear Information System (INIS)

    Wojtowicz, J.; Pawlak, B.; Lehman, Z.; Karwowski, A.; Akademia Medyczna, Poznan

    1984-01-01

    Thirty-two patients with cardiomyopathy, 25 with hypertrophic and 7 with dilated form were examined by cardiac catheterisation, left ventriculography, selective coronary angiography and ungated cardiac computed tomography. Diffuse hypertrophy, localized hypertrophy and dilated cardiomyopathy were diagnosed and assessed quantitatively based on CT linear, surface and volumetric parameters of cardiac morphology. Absolute septal thickness and left ventricular mass measured in CT image are the most discriminative attributes. (orig.)

  9. Effect of prophylactic digitalization on the development of myocardial hypertrophy.

    Science.gov (United States)

    Cutilletta, A F; Rudnik, M; Arcilla, R A; Straube, R

    1977-11-01

    The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

  10. The FIFA medical emergency bag and FIFA 11 steps to prevent sudden cardiac death: setting a global standard and promoting consistent football field emergency care.

    Science.gov (United States)

    Dvorak, Jiri; Kramer, Efraim B; Schmied, Christian M; Drezner, Jonathan A; Zideman, David; Patricios, Jon; Correia, Luis; Pedrinelli, André; Mandelbaum, Bert

    2013-12-01

    Life-threatening medical emergencies are an infrequent but regular occurrence on the football field. Proper prevention strategies, emergency medical planning and timely access to emergency equipment are required to prevent catastrophic outcomes. In a continuing commitment to player safety during football, this paper presents the FIFA Medical Emergency Bag and FIFA 11 Steps to prevent sudden cardiac death. These recommendations are intended to create a global standard for emergency preparedness and the medical response to serious or catastrophic on-field injuries in football.

  11. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  12. Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease.

    Science.gov (United States)

    Burkhardt, Barbara E U; Rücker, Gerta; Stiller, Brigitte

    2015-03-25

    Children with congenital heart disease often undergo heart surgery at a young age. They are at risk for postoperative low cardiac output syndrome (LCOS) or death. Milrinone may be used to provide inotropic and vasodilatory support during the immediate postoperative period. This review examines the effectiveness of prophylactic postoperative use of milrinone to prevent LCOS or death in children having undergone surgery for congenital heart disease. Electronic and manual literature searches were performed to identify randomised controlled trials. We searched CENTRAL, MEDLINE, EMBASE and Web of Science in February 2014 and conducted a top-up search in September 2014 as well as clinical trial registries and reference lists of published studies. We did not apply any language restrictions. Only randomised controlled trials were selected for analysis. We considered studies with newborn infants, infants, toddlers, and children up to 12 years of age. Two review authors independently extracted data according to a pre-defined protocol. We obtained additional information from all study authors. Three of the five included studies compared milrinone versus levosimendan, one study compared milrinone with placebo, and one compared milrinone verus dobutamine, with 101, 242, and 50 participants, respectively. Three trials were at low risk of bias while two were at higher risk of bias. The number and definitions of outcomes were non-uniform as well. In one study comparing two doses of milrinone and placebo, there was some evidence in an overall comparison of milrinone versus placebo that milrinone lowered risk for LCOS (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.28 to 0.96; 227 participants). The results from two small studies do not provide enough information to determine whether milrinone increases the risk of LCOS when compared to levosimendan (RR 1.22, 95% CI 0.32 to 4.65; 59 participants). Mortality rates in the studies were low, and there was insufficient evidence to

  13. Clinical evaluation of left ventricular wall thickness by combined technique with gated planer 201Tl image and gated cardiac pool image

    International Nuclear Information System (INIS)

    Nakai, Kenji; Katsuragawa, Shigehiko; Takahashi, Tsuneo; Matsushita, Kazuo; Kawamura, Akiyoshi

    1983-01-01

    To evaluate the left ventricular (LV) wall thickness, combined technique with gated planer 201-Thallium image and gated cardiac pool image was applied to 6 patients with hypertrophic cardiomyopathy (HCM) and 4 patients with secondary hypertrophy due to hypertension (HHD) proven by electrocardiography and ultrasonic-echocardiography. Scintigraphic pattern of hypertrophy on reconstructed planer 201 Tl image showed diffuse or asymmetrical apical hypertrophy in HHD, asymmetrical septal hypertrophy in HCM. It was very interesting that abnormal perfusion was shown in 201 Tl image, despite symmetrical hypertrophy in echocardiography. This techniques provided useful information for evaluating the LV wall thickness and cardiac performance. (author)

  14. Clinical evaluation of left ventricular wall thickness by combined technique with gated planer /sup 201/Tl image and gated cardiac pool image

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, Kenji; Katsuragawa, Shigehiko; Takahashi, Tsuneo; Matsushita, Kazuo; Kawamura, Akiyoshi

    1983-11-01

    To evaluate the left ventricular (LV) wall thickness, a combined technique with gated planer 201-thallium image and gated cardiac pool image was applied to 6 patients with hypertrophic cardiomyopathy (HCM) and 4 patients with secondary hypertrophy due to hypertension (HHD) proven by electrocardiography and ultrasonic-echocardiography. Scintigraphic pattern of hypertrophy on reconstructed planer /sup 201/Tl image showed diffuse or asymmetrical apical hypertrophy in HHD, asymmetrical septal hypertrophy in HCM. It was very interesting that abnormal perfusion was shown in /sup 201/Tl image, despite symmetrical hypertrophy in echocardiography. This techniques provided useful information for evaluating the LV wall thickness and cardiac performance.

  15. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

    Science.gov (United States)

    Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

    2014-10-01

    Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  16. Improving Surveillance and Prevention of Surgical Site Infection in Pediatric Cardiac Surgery.

    Science.gov (United States)

    Cannon, Melissa; Hersey, Diane; Harrison, Sheilah; Joy, Brian; Naguib, Aymen; Galantowicz, Mark; Simsic, Janet

    2016-03-01

    Postoperative cardiovascular surgical site infections are preventable events that may lead to increased morbidity, mortality, and health care costs. To improve surgical wound surveillance and reduce the incidence of surgical site infections. An institutional review of surgical site infections led to implementation of 8 surveillance and process measures: appropriate preparation the night before surgery and the day of surgery, use of appropriate preparation solution in the operating room, appropriate timing of preoperative antibiotic administration, placement of a photograph of the surgical site in the patient's chart at discharge, sending a photograph of the surgical site to the patient's primary care physician, 30-day follow-up of the surgical site by an advanced nurse practitioner, and placing a photograph of the surgical site obtained on postoperative day 30 in the patient's chart. Mean overall compliance with the 8 measures from March 2013 through February 2014 was 88%. Infections occurred in 10 of 417 total operative cases (2%) in 2012, in 8 of 437 total operative cases (2%) in 2013, and in 7 of 452 total operative cases (1.5%) in 2014. Institution of the surveillance process has resulted in improved identification of suspected surgical site infections via direct rather than indirect measures, accurate identification of all surgical site infections based on definitions of the National Healthcare Safety Network, collaboration with all persons involved, and enhanced communication with patients' family members and referring physicians. ©2016 American Association of Critical-Care Nurses.

  17. [Asymmetric hypertrophy of the masticatory muscles].

    Science.gov (United States)

    Arzul, L; Corre, P; Khonsari, R H; Mercier, J-M; Piot, B

    2012-06-01

    Hypertrophy of the masticatory muscles most commonly affects the masseter. Less common cases of isolated or associated temporalis hypertrophy are also reported. Parafunctional habits, and more precisely bruxism, can favor the onset of the hypertrophy. This condition is generally idiopathic and can require both medical and/or surgical management. A 29-year-old patient was referred to our department for an asymmetric swelling of the masticatory muscles. Physical examination revealed a bilateral hypertrophy of the masticatory muscles, predominantly affecting the right temporalis and the left masseter. Major bruxism was assessed by premature dental wearing. The additional examinations confirmed the isolated muscle hypertrophy. Benign asymmetric hypertrophy of the masticatory muscles promoted by bruxism was diagnosed. Treatment with injections of type A botulinum toxin was conducted in association with a splint and relaxation. Its effectiveness has been observed at six months. Few cases of unilateral or bilateral temporalis hypertrophy have been reported, added to the more common isolated masseter muscles hypertrophy. The diagnosis requires to rule out secondary hypertrophies and tumors using Magnetic Resonance Imaging. The condition is thought to be favoured by parafunctional habits such as bruxism. The conservative treatment consists in reducing the volume of the masticatory muscles using intramuscular injections of type A botulinum toxin. Other potential conservative treatments are wearing splints and muscle relaxant drugs. Surgical procedures aiming to reduce the muscle volume and/or the bone volume (mandibular gonioplasty) can be proposed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Prevention of deterioration of ventricular fibrillation by basic life support during out-of-hospital cardiac arrest

    NARCIS (Netherlands)

    Waalewijn, Reinier A.; Nijpels, Marië A.; Tijssen, Jan G.; Koster, Rudolph W.

    2002-01-01

    Survival of cardiac arrest is improved by basic life support (BLS). This study investigated the relationship between ventricular fibrillation (VF) characteristics and survival. In a 2-year prospective study out-of-hospital witnessed non-traumatic cardiac arrests were observed. The probabilities of

  19. Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease

    Directory of Open Access Journals (Sweden)

    Sherin Saheera

    2017-10-01

    Full Text Available Background Cardiac stem cells (CSCs play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. Methods To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Results Functional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment. Discussion As anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of

  20. Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

    Science.gov (United States)

    Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank

    2016-05-10

    Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

  1. The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ford, Andrew H; Flicker, Leon; Passage, Jurgen; Wibrow, Bradley; Anstey, Matthew; Edwards, Mark; Almeida, Osvaldo P

    2016-01-28

    Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015).

  2. Genetics Home Reference: myostatin-related muscle hypertrophy

    Science.gov (United States)

    ... Twitter Home Health Conditions Myostatin-related muscle hypertrophy Myostatin-related muscle hypertrophy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Myostatin-related muscle hypertrophy is a rare condition characterized ...

  3. Comparative study of the antioxidant properties of monocarbonyl curcumin analogues C66 and B2BrBC in isoproteranol induced cardiac damage.

    Science.gov (United States)

    Hadzi-Petrushev, Nikola; Bogdanov, Jane; Krajoska, Jovanka; Ilievska, Jovana; Bogdanova-Popov, Biljana; Gjorgievska, Elizabeta; Mitrokhin, Vadim; Sopi, Ramadan; Gagov, Hristo; Kamkin, Andre; Mladenov, Mitko

    2018-03-15

    To test the antioxidant properties of the newly synthesized (2E,6E)-2,6-bis(2-bromobenzylidene)cyclohexanone (B2BrBC) in parallel with C66 in rats with cardiac hypertrophy. The protective effects of both C66 and B2BrBC against oxidative stress in rats with cardiac hypertrophy, was studied by evaluating the activity of antioxidant enzymes, the relationship between the ratio of the activities of the antioxidant enzymes R = SOD/(GPx + CAT) and levels of thiols and lipid peroxidation in the heart. In order to gain better understanding of the antioxidant properties of the studied compounds, computational methods were utilized. The properties of selected structurally related derivatives were obtained on optimized geometries for ground states, using semi-empirical PM3 quantum mechanical calculations. The ratio R shows disequilibrium in rats with induced hypertrophy (p antioxidant. The obtained results indicated that the antioxidant ability of B2BrBC is positively associated with the catalytic SOD and GPx activities expressed through preserved t-SH levels. It seems plausible that for a compound to exhibit antioxidant activity, as most of the 2,6-bis(benzylidene)cyclohexanones do, they should be good electron donors. Understanding the relationship between cardiac hypertrophy induced oxidative injuries and supporters of endogenous reparatory machinery will help in establishing the beneficial role of adequate antioxidant supplementation. In this study reliable data on the preventive effects of newly synthesized symmetric monocarbonyl curcumin analogue B2BrBC and its role in the prevention of oxidative injuries on three levels (enzymatic, protein and lipid), in the heart hypertrophic onset, were obtained. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Intersections between cardiac physiology, emotion regulation and interpersonal warmth in preschoolers: Implications for drug abuse prevention from translational neuroscience.

    Science.gov (United States)

    Clark, Caron A C; Skowron, Elizabeth A; Giuliano, Ryan J; Fisher, Philip A

    2016-06-01

    Early childhood is characterized by dramatic gains in emotion regulation skills that support social adjustment and mental health. Understanding the physiological substrates of healthy emotion regulation may offer new directions for altering trajectories toward initiation and escalation of substance abuse. Here, we describe the intersections between parasympathetic and sympathetic tone, emotion regulation and prosocial behavior in a high-risk sample of preschoolers. Fifty-two 3-6 year old children completed an assessment of attention regulation in response to affective stimuli. Cardiac respiratory sinus arrhythmia, an index of parasympathetic tone, and pre-ejection period, a marker of sympathetic activation, were recorded at rest and while children engaged in social interactions with their mothers and an unfamiliar research assistant. Mothers reported on children's emotional reactivity and prosocial behavior. Controlling for age and psychosocial risk, higher parasympathetic tone predicted better attention regulation in response to angry emotion and higher levels of prosocial behavior, whereas a reciprocal pattern of higher parasympathetic tone and lower sympathetic arousal predicted better attention in response to positive emotion and lower emotional reactivity. Children exposed to fewer risk factors and higher levels of maternal warmth were more able to sustain a high level of parasympathetic tone during interaction episodes. Findings suggest that autonomic measures represent biomarkers for socio-emotional competence in young children. They also point to the importance of early experiences in the establishment of physiological regulation and the promise of family-based intervention to promote healthy emotion regulation and prevent substance dependence in high-risk populations. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

    Science.gov (United States)

    García-González, P; Fabregat-Andrés, Ó; Cozar-Santiago, P; Sánchez-Jurado, R; Estornell-Erill, J; Valle-Muñoz, A; Quesada-Dorador, A; Payá-Serrano, R; Ferrer-Rebolleda, J; Ridocci-Soriano, F

    2016-01-01

    Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  6. Meta-Analysis of Sodium Bicarbonate Therapy for Prevention of Cardiac Surgery-Associated Acute Kidney Injury.

    Science.gov (United States)

    Kim, Jun Hyun; Kim, Hyun Jung; Kim, Ji Yeon; Ahn, Hyeong sik; Ahn, Il Min; Choe, Won Joo; Lim, Choon-Hak

    2015-10-01

    The aim of this study was to determine whether or not perioperative administration of sodium bicarbonate had a preventive effect on cardiac surgery-associated acute kidney injury (CSA-AKI) as shown in randomized controlled trials. The authors conducted a systematic review and meta-analysis using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and KoreaMed. The authors searched MEDLINE, EMBASE, CENTRAL, and KoreaMed without language and date restrictions. They used both MeSH and free-text terms to identify relevant studies. Electronic searches were undertaken on July 31, 2014. Five randomized controlled studies included in this review. There were no differences in the development of CSA-AKI among patients in the sodium bicarbonate group compared with those in the control group (5 trials, 1,092 patients; n = 233 of 547 in sodium bicarbonate (SB) group versus 225 of 545 in control group (SC); risk ratio (RR), 0.95; 95% confidence interval (CI), 0.74-1.22. Also, there were no statistical differences in in-hospital mortality (3 trials, 573 patients; n = 21 of 288 in SB versus 14 of 285 in SC; RR, 1.44; 95% CI, 0.76-2.72), need for renal replacement therapy (4 trials, 1,000 patients; n = 21 of 503 in SB versus 23 of 497 in SC; RR, 0.90; 95% CI, 0.50-1.60), length of stay in the intensive care unit (ICU) (hours) (4 trials, n = 969 patients, weighted men difference (WMD), 2.17; 95% CI, -1.15-5.49), and length of ventilation (hours) (4 trials, 969 patients; WMD, 0.34; 95% CI,-0.80-1.48). Perioperative administration of sodium bicarbonate did not reduce the rate of CSA-AKI in randomized controlled trials. Therefore, use of perioperative administration of sodium bicarbonate for the prevention of CSA-AKI is questionable. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

    Science.gov (United States)

    Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

    2013-05-01

    This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

  8. Cardiac ablation

    Directory of Open Access Journals (Sweden)

    Kelly Ratheal

    2016-01-01

    Full Text Available Cardiac ablation is a procedure that uses either radiofrequency or cryothermal energy to destroy cells in the heart to terminate and/or prevent arrhythmias. The indications for cardiac catheter ablation include refractory, symptomatic arrhythmias, with more specific guidelines for atrial fibrillation in particular. The ablation procedure itself involves mapping the arrhythmia and destruction of the aberrant pathway in an effort to permanently prevent the arrhythmia. There are many types of arrhythmias, and they require individualized approaches to ablation based on their innately different electrical pathways. Ablation of arrhythmias, such as Wolff-Parkinson-White syndrome, AV nodal reentrant tachycardia, and atrial-fibrillation, is discussed in this review. Ablation has a high success rate overall and minimal complication rates, leading to improved quality of life in many patients.

  9. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    Science.gov (United States)

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  10. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes

    OpenAIRE

    Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-01-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubic...

  11. Cardiac regeneration therapy: connections to cardiac physiology.

    Science.gov (United States)

    Takehara, Naofumi; Matsubara, Hiroaki

    2011-12-01

    Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

  12. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As

  13. Effects of Resistance Training on Ventricular Function and Hypertrophy in a Rat Model

    Science.gov (United States)

    Barauna, Valério Garrone; Rosa, Kaleizu Teodoro; Irigoyen, Maria Cláudia; de Oliveira, Edilamar Menezes

    2007-01-01

    Objective: The purpose of this study was to follow the ventricular function and cardiac hypertrophy in rats undergoing a resistance-training program for a period of 3 months. Design: Forty animals were divided into two major groups: control (n=16) and resistance trained (n=24). From the resistance-trained group, 12 animals were resistance trained for 1 month and another 12 for 3 months. The resistance-training protocol was performed with 4 sets of 12 repetitions using 65% to 75% of one repetition maximum (maximum lifted weight with the exercise apparatus). Methods: Echocardiographic analysis was performed at the beginning of the resistance-training period and at the end of each month. The repetition maximum was measured every 2 weeks. Cardiac hypertrophy was determined by echocardiography, by the absolute weight of the cardiac chambers and by histology of the left ventricle. Results: Before resistance training, both groups had similar repetition maximums, ranging from 1.8-fold to 2-fold the body weight; however, at the end of the resistance-training period, the repetition maximum of the resistance-trained group was 6-fold greater than the body weight. The left ventricular mass as assessed by echocardiography was 8%, 12% and 16% larger in the resistance-trained group than in the control group in the first, second and third months, respectively. This hypertrophy showed a similar increase in the interventricular septum and in the free posterior wall mass. There was no reduction in the end-diastolic left ventricular internal diameter during the 3-month resistance-training period. Systolic function did not differ between the groups throughout the resistance-training period. Conclusion: Resistance training induces the development of concentric cardiac hypertrophy without ventricular dysfunction or cavity reduction. Although diastolic function was not completely investigated, we cannot exclude the possibility that resistance training results in diastolic dysfunction. PMID

  14. Visualization of hypertrophied papillary muscle mimicking left ventricular mass on gated blood pool and T1-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Bunko, H.; Nakajima, K.; Tonami, N.; Asanoi, H.; Hisada, K.

    1981-01-01

    A sixty-year old man with acute myocardial infarction was incidentally found to have a hypertrophied anterolateral papillary muscle (ALPPM) of the left ventricle on gated blood pool (GBP) and T1-201 myocardial perfusion images. Hypertrophy of the ALPPM was visualized as a movable defect in the lateral basal area on GBP imaging throughout the cardiac cycle and on the TI-201 study as a radionuclide accumulating structure, consistent with the defect in the GBP. A combination of these findings may suggest the presence of a hypertrophied papillary muscle of the left ventricle

  15. Short-term minoxidil use associated with pericardial effusion and cardiac tamponade: an uncommon presentation.

    Science.gov (United States)

    Pasala, Krishna K; Gujja, Karthik; Prabhu, Hejmadi; Vasavada, Balendu; Konka, Sudarsanam

    2012-11-01

    A 48-year-old man presented with complaints of shortness of breath and lower extremity swelling. His medical history was significant for hypertension on minoxidil and recent intracerebellar hemorrhage. Electrocardiography showed sinus tachycardia with left ventricular hypertrophy, and cardiomegaly was noted in the chest x-ray. The patient was hypertensive and tachypneic on admission. An echocardiogram taken immediately showed a large pericardial effusion with evidence of cardiac tamponade. He underwent immediate pericardiocentesis with drainage of 900 mL of pericardial fluid with significant improvement in the symptoms. Analysis of the pericardial fluid proved to be nondiagnostic. Infectious and rheumatologic causes were ruled out. After an extensive battery of tests, not yielding any diagnostic results, the pericardial effusion was attributed to minoxidil therapy. Closer monitoring is needed to prevent potentially fatal complications such as cardiac tamponade as in our patient.

  16. PREVENTION OF LEFT VENTRICLE SYSTOLIC DYSFUNCTION IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST SEGMENT ELEVATION AFTER CARDIAC REVASCULARIZATION

    OpenAIRE

    A. L. Alyavi; B. A. Alyavi; M. L. Kenzhaev; S. R. Kenzhaev

    2009-01-01

    Aim. To study effects of bioflavonoid quercetin (corvitin) on left ventricle (LV) systolic dysfunction in patients with acute coronary syndrome with ST segment elevation (ACS+ST) after cardiac revascularization.Material and methods. 60 patients with ACS+ST (44,2±1,3 y.o.) were examined. Patients were admitted to hospital within 6 hours after complaints beginning. Patients were randomized in two groups. 30 patients of group A had standard therapy and cardiac revascularization. 30 patients of g...

  17. The thickened left ventricle: etiology, differential diagnosis and implications for cardiovascular radiology; Der dicke linke Ventrikel. Ursachen und Differenzialdiagnose der linksventrikulaeren Hypertrophie und Implikationen fuer die kardiovaskulaere Radiologie

    Energy Technology Data Exchange (ETDEWEB)

    Bischoff, P.; Barkhausen, J.; Hunold, P. [Universitaetsklinikum Schleswig-Holstein, Luebeck (Germany). Klinik fuer Radiologie und Nuklearmedizin; Radke, P.W. [Universitaetsklinikum Schleswig Holstein, Luebeck (Germany). Medizinische Klinik II

    2012-08-15

    Hypertrophy of the left ventricular myocardium is a common finding and can be reliably detected by echocardiography, CT and MRI. Common causes include diseases associated with increased cardiac afterload as well as primary and secondary cardiomyopathy. With the opportunity to determine functional parameters and myocardial mass precisely as well as to detect structural changes of the cardiac muscle simultaneously, cardiac MRI is the most precise imaging method for quantifying left ventricular hypertrophy as well as determining the cause and the exact characterization of the myocardial changes. It is mandatory, however, to create a flexible, individually adapted examination protocol. This review presents useful diagnostic algorithms in relation to different underlying pathologies in patients with left ventricular hypertrophy. (orig.)

  18. Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD.

    Science.gov (United States)

    Schneider, Markus P; Raff, Ulrike; Kopp, Christoph; Scheppach, Johannes B; Toncar, Sebastian; Wanner, Christoph; Schlieper, Georg; Saritas, Turgay; Floege, Jürgen; Schmid, Matthias; Birukov, Anna; Dahlmann, Anke; Linz, Peter; Janka, Rolf; Uder, Michael; Schmieder, Roland E; Titze, Jens M; Eckardt, Kai-Uwe

    2017-06-01

    The pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23 sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23-78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP ( r =0.33, P =0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass ( r =0.56, P skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients. Copyright © 2017 by the American Society of Nephrology.

  19. Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

    Science.gov (United States)

    Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

    2017-08-01

    Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions

  20. The antioxidant edaravone prevents cardiac dysfunction by suppressing oxidative stress in type 1 diabetic rats and in high-glucose-induced injured H9c2 cardiomyoblasts.

    Science.gov (United States)

    Ji, Lei; Liu, Yingying; Zhang, Ying; Chang, Wenguang; Gong, Junli; Wei, Shengnan; Li, Xudong; Qin, Ling

    2016-09-01

    Edaravone, a radical scavenger, has been recognized as a potential protective agent for cardiovascular diseases. However, little is known about the effect of edaravone in cardiac complications associated with diabetes. Here, we have demonstrated that edaravone prevents cardiac dysfunction and apoptosis in the streptozotocin-induced type 1 diabetic rat heart. Mechanistic studies revealed that edaravone treatment improved cardiac function and restored superoxide dismutase levels. In addition, treatment of diabetic animals by edaravone increased protein expressions of sirtuin-1 (SIRT-1), peroxisome proliferator activated receptor γ coactivator α (PGC-1α), nuclear factor like-2 (NRF-2), and B cell lymphoma 2 (Bcl-2), and reduced protein expressions of Bax and Caspase-3 compared to the control group. High glucose incubation resulted in the production of reactive oxygen species (ROS) and cell death. Treatment of high-glucose-incubated H9c2 cells by edaravone reduced ROS production and cell death. In addition, the treatment of high-glucose-incubated H9c2 cells by edaravone increased the activity of antioxidative stress by increasing SIRT-1, PGC-1α, and NRF-2, and this treatment also reduced apoptosis by increasing Bcl-2 expression and reducing Bax and Caspase-3 expressions. Knockdown SIRT-1 with small interferer RNA abolished the effects of edaravone. Overall, our data demonstrated that edaravone may be an effective agent against the development of diabetic cardiomyopathy.

  1. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

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    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  2. Asymmetric septal hypertrophy of sporadic form with abnormal thallium perfusion and myocardial enzymes

    International Nuclear Information System (INIS)

    Nagata, Seiki; Minamikawa, Tetsuhiro; Park, Yung-Dae; Nishimura, Tsunehiko; Yutani, Chikao; Ohmori, Fumio; Sakakibara, Hiroshi; Nimura, Yasuharu

    1986-01-01

    Asymmetric septal hypertrophy with abnormal thallium scintigram and elevated cardiac enzymes were observed in five patients and were studied with special reference to the clinical significance of their clinicopathological features. They were not familial cardiomyopathy patients. Two of the five patients (Cases 1 and 2) exhibited the clinical features characteristic of hypertrophic cardiomyopathy without abnormal thallium perfusion and serum cardiac enzyme levels. A right endomyocardial biopsy for Case 1 disclosed myocardial fibrosis in addition to hypertrophy and disarray of myocardial fibers. The left ventricular cavities of two other patients (Cases 4 and 5) tended to be dilated with signs of impaired systolic function and asymmetric septal hypertrophy. A regional area of reduced thickness was observed in the medial portion of the left ventricular posterior wall of Case 4. The remaining case (Case 3) exhibited left ventricular dilatation and reduced left ventricular systolic function, disproportionate hypertrophy, and had clinical signs of congestive heart failure. Necropsy disclosed massive fibrosis and diffuse disarray of myocardial fibers. Some patients with familial hypertrophic cardiomyopathy progress to exhibit clinical features of dilated cardiomyopathy in the termimal stages, and have massive fibrosis of the myocardium histologically. Thallium scintigraphic abnormalities and elevated serum levels of cardiac enzymes, especially the LDH 1 isoenzyme, in patients with hypertrophic cardiomyopathy may be a meaningful indicator of such progression in its early stages. The five patients in the present study exhibited a variety of clinical and histological features which may comprise a spectrum of clinical conditions during the progression from hypertrophic cardiomyopathy to a condition like dilated cardiomyopathy, similar to that in familial patients. This progression and the factors promoting it should be studied further in the near future. (author)

  3. Hypocretin-1 (orexin A) prevents the effects of hypoxia/hypercapnia and enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Dergacheva, O; Philbin, K; Bateman, R; Mendelowitz, D

    2011-02-23

    Hypocretins (orexins) are hypothalamic neuropeptides that play a crucial role in regulating sleep/wake states and autonomic functions including parasympathetic cardiac activity. We have recently demonstrated stimulation of the lateral paragigantocellular nucleus (LPGi), the nucleus which is thought to play a role in rapid eye movement (REM) sleep control, activates an inhibitory pathway to preganglionic cardiac vagal neurons in the nucleus ambiguus (NA). In this study we test the hypothesis that hypocretin-1 modulates the inhibitory neurotransmission to cardiac vagal neurons evoked by stimulation of the LPGi using whole-cell patch-clamp recordings in an in vitro brain slice preparation from rats. Activation of hypocretin-1 receptors produced a dose-dependent and long-term facilitation of GABAergic postsynaptic currents evoked by electrical stimulation of the LPGi. Hypoxia/hypercapnia diminished LPGi-evoked GABAergic current in cardiac vagal neurons and this inhibition by hypoxia/hypercapnia was prevented by pre-application of hypocretin-1. The action of hypocretin-1 was blocked by the hypocretin-1 receptor antagonist SB-334867. Facilitation of LPGi-evoked GABAergic current in cardiac vagal neurons under both normal condition and during hypoxia/hypercapnia could be the mechanism by which hypocretin-1 affects parasympathetic cardiac function and heart rate during REM sleep. Furthermore, our findings indicate a new potential mechanism that might be involved in the cardiac arrhythmias, bradycardia, and sudden cardiac death that can occur during sleep. Copyright © 2011. Published by Elsevier Ltd.

  4. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    NARCIS (Netherlands)

    Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

    2016-01-01

    textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

  5. Distinct cardiac transcriptional profiles defining pregnancy and exercise.

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    Eunhee Chung

    Full Text Available BACKGROUND: Although the hypertrophic responses of the heart to pregnancy and exercise are both considered to be physiological processes, they occur in quite different hormonal and temporal settings. In this study, we have compared the global transcriptional profiles of left ventricular tissues at various time points during the progression of hypertrophy in exercise and pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: The following groups of female mice were analyzed: non-pregnant diestrus cycle sedentary control, mid-pregnant, late-pregnant, and immediate-postpartum, and animals subjected to 7 and 21 days of voluntary wheel running. Hierarchical clustering analysis shows that while mid-pregnancy and both exercise groups share the closest relationship and similar gene ontology categories, late pregnancy and immediate post-partum are quite different with high representation of secreted/extracellular matrix-related genes. Moreover, pathway-oriented ontological analysis shows that metabolism regulated by cytochrome P450 and chemokine pathways are the most significant signaling pathways regulated in late pregnancy and immediate-postpartum, respectively. Finally, increases in expression of components of the proteasome observed in both mid-pregnancy and immediate-postpartum also result in enhanced proteasome activity. Interestingly, the gene expression profiles did not correlate with the degree of cardiac hypertrophy observed in the animal groups, suggesting that distinct pathways are employed to achieve similar amounts of cardiac hypertrophy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that cardiac adaptation to the later stages of pregnancy is quite distinct from both mid-pregnancy and exercise. Furthermore, it is very dynamic since, by 12 hours post-partum, the heart has already initiated regression of cardiac growth, and 50 genes have changed expression significantly in the immediate-postpartum compared to late-pregnancy. Thus, pregnancy

  6. Postural control in women with breast hypertrophy

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    Alessandra Ferreira Barbosa

    2012-07-01

    Full Text Available OBJECTIVES: The consequences of breast hypertrophy have been described based on the alteration of body mass distribution, leading to an impact on psychological and physical aspects. The principles of motor control suggest that breast hypertrophy can lead to sensorimotor alterations and the impairment of body balance due to postural misalignment. The aim of this study is to evaluate the postural control of women with breast hypertrophy under different sensory information conditions. METHOD: This cross-sectional study included 14 women with breast hypertrophy and 14 without breast hypertrophy, and the mean ages of the groups were 39 ±15 years and 39±16 years, respectively. A force platform was used to assess the sensory systems that contribute to postural control: somatosensory, visual and vestibular. Four postural conditions were sequentially tested: eyes open and fixed platform, eyes closed and fixed platform, eyes open and mobile platform, and eyes closed and mobile platform. The data were processed, and variables related to the center of pressure were analyzed for each condition. The Kruskal-Wallis test was used to compare the conditions between the groups for the area of center of pressure displacement and the velocity of center of pressure displacement in the anterior-posterior and medial-lateral directions. The alpha level error was set at 0.05. RESULTS: Women with breast hypertrophy presented an area that was significantly higher for three out of four conditions and a higher velocity of center of pressure displacement in the anterior-posterior direction under two conditions: eyes open and mobile platform and eyes closed and mobile platform. CONCLUSIONS: Women with breast hypertrophy have altered postural control, which was demonstrated by the higher area and velocity of center of pressure displacement.

  7. Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy.

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    Ming Xu

    2007-02-01

    Full Text Available Pressure overload-induced hypertrophy is a key step leading to heart failure. The Ca(2+-induced Ca(2+ release (CICR process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca(2+ channel (LCC and ryanodine receptors (RyRs in aortic stenosis rat models of compensated (CHT and decompensated (DHT hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of "intermolecular failure." Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca(2+ release, visualized as "Ca(2+ spikes," became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca(2+ transients in CHT. These data suggested that, within a certain limit, termed the "stability margin," mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of "hidden" intermolecular failure in CHT has important clinical implications.

  8. 123I-MIBG myocardial imaging in hypertensive patients. Abnormality progresses with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Mitani, Isao; Sumita, Shinichi; Takahashi, Nobukazu; Ochiai, Hisao; Ishii, Masao

    1996-01-01

    Twenty-seven patients with essential hypertension were prospectively studied with 123 I-labeled metaiodobenzyl-guanidine ( 123 I-MIBG) to assess the presence and location of impaired sympathetic innervation in hypertrophied myocardium. Thirteen patients had left ventricular hypertrophy on echocardiography, and 14 had normal echocardiograms. The wash-out ratio of 123 I-MIBG in these two groups did not differ significantly (35.3±6.1 and 35.4±5.1) but was higher than in control subjects (29.4±6.7). The delayed heart-to-mediastinum count ratio was lower in the patients with hypertrophy than in the patients without hypertrophy (1.93±0.28 and 2.22±0.21; p<0.05) and the control subjects (1.93±0.28 and 2.33±0.25; p<0.05). On SPECT imaging, abnormalities in segmental uptake were frequent at the posterior and postero-lateral wall in both groups, although the hypertrophic group had more significant impairment. Our results lead to the hypothesis that hypertension in more advanced stages may be associated not only with hypertrophic changes but also with more advanced regional impairment of cardiac sympathetic innervation. (author)

  9. VO(2peak), myocardial hypertrophy, and myocardial blood flow in endurance-trained men.

    Science.gov (United States)

    Laaksonen, Marko S; Heinonen, Ilkka; Luotolahti, Matti; Knuuti, Juhani; Kalliokoski, Kari K

    2014-08-01

    Endurance training induces cardiovascular and metabolic adaptations, leading to enhanced endurance capacity and exercise performance. Previous human studies have shown contradictory results in functional myocardial vascular adaptations to exercise training, and we hypothesized that this may be related to different degrees of hypertrophy in the trained heart. We studied the interrelationships between peak aerobic power (V˙O2peak), myocardial blood flow (MBF) at rest and during adenosine-induced vasodilation, and parameters of myocardial hypertrophy in endurance-trained (ET, n = 31) and untrained (n = 17) subjects. MBF and myocardial hypertrophy were studied using positron emission tomography and echocardiography, respectively. Both V˙O2peak (P negatively with adenosine-stimulated MBF, but when LV mass was taken into account as a partial correlate, this correlation disappeared. The present results show that increased LV mass in ET subjects explains the reduced hyperemic myocardial perfusion in this subject population and suggests that excessive LV hypertrophy has negative effect on cardiac blood flow capacity.

  10. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

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    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  11. A Benign Cardiac Growth but Not So Indolent

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    Adil S. Wani

    2016-01-01

    Full Text Available Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis.

  12. A Benign Cardiac Growth but Not So Indolent

    Science.gov (United States)

    Reddy, Sahadev T.; Biederman, Robert W. W.

    2016-01-01

    Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis. PMID:27293911

  13. Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review

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    Karina Sanches Machado d’Almeida

    2018-01-01

    Full Text Available Background: Heart failure (HF is a complex syndrome and is recognized as the ultimate pathway of cardiovascular disease (CVD. Studies using nutritional strategies based on dietary patterns have proved to be effective for the prevention and treatment of CVD. Although there are studies that support the protective effect of these diets, their effects on the prevention of HF are not clear yet. Methods: We searched the Medline, Embase, and Cochrane databases for studies that examined dietary patterns, such as dietary approaches to stop hypertension (DASH diet, paleolithic, vegetarian, low-carb and low-fat diets and prevention of HF. No limitations were used during the search in the databases. Results: A total of 1119 studies were identified, 14 met the inclusion criteria. Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were found. The Mediterranean and DASH diets showed a protective effect on the incidence of HF and/or worsening of cardiac function parameters, with a significant difference in relation to patients who did not adhere to these dietary patterns. Conclusions: It is observed that the adoption of Mediterranean or DASH-type dietary patterns may contribute to the prevention of HF, but these results need to be analyzed with caution due to the low quality of evidence.

  14. Gualou Xiebai Decoction, a Traditional Chinese Medicine, Prevents Cardiac Reperfusion Injury of Hyperlipidemia Rat via Energy Modulation.

    Science.gov (United States)

    Yan, Lu-Lu; Zhang, Wei-Yang; Wei, Xiao-Hong; Yan, Li; Pan, Chun-Shui; Yu, Yang; Fan, Jing-Yu; Liu, Yu-Ying; Zhou, Hua; Han, Jing-Yan; Yao, Xin-Sheng

    2018-01-01

    Background: Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. Methods: After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Results: Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Conclusions: Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.

  15. An economic evaluation of two interventions for the prevention of post-surgical infections in cardiac surgery.

    Science.gov (United States)

    del Diego Salas, J; Orly de Labry Lima, A; Espín Balbino, J; Bermúdez Tamayo, C; Fernández-Crehuet Navajas, J

    2016-01-01

    To conduct a cost-effectiveness analysis that compares two prophylactic protocols for treating post-surgical infections in cardiac surgery. A cost effectiveness analysis was done by using a decision tree to compare two protocols for prophylaxis of post-surgical infections (Protocol A: Those patient with positive test to methicillin-resistant Staphylococcus aureus (MRSA) colonization received muripocin (twice a day during a two-week period), with no follow-up verification. Those who tested negative did not receive the prophylaxis treatment; Protocol B: all patients received the mupirocin treatment). The number of post-surgical infections averted was the measure of effectiveness from the health system's perspective, 30 days following the surgery. The incidence of infections and complications was obtained from two cohorts of patients who underwent cardiac surgery Hospital. The times for applying the two protocols were validated by experts. They cost were calculated from the hospital's analytical accounting management system and Pharmaceutical Service. Only direct costs were taken into account, no discount rates were applied. Incremental cost-effectiveness ratio (ICER) was calculated. A probabilistic sensitivity analysis was performed. A total of 1118 patients were included (721 in Protocol A and 397 in Protocol B). No statistically significant differences were found in age, sex, diabetes, exitus or length of hospital stay between the two protocols. In the control group the rate of infection was 15.3%, compared with 11.3% in the intervention group. Protocol B proves to be more effective and at a lower cost, yielding an ICER of €32,506. Universal mupirocin prophylaxis against surgical site infections (SSI) in cardiac surgery as a dominant strategy, because it shows a lower incidence of infections and cost savings, versus the strategy to treat selectively patients according to their test results prior screening. Copyright © 2015 SECA. Published by Elsevier Espana. All

  16. Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

    Science.gov (United States)

    Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

    2016-12-15

    Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

    Science.gov (United States)

    Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi

    2015-12-01

    Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo.

    Science.gov (United States)

    Bueno, O F; De Windt, L J; Lim, H W; Tymitz, K M; Witt, S A; Kimball, T R; Molkentin, J D

    2001-01-19

    Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.

  19. Mitochondrial oxidative stress and cardiac ageing.

    Science.gov (United States)

    Martín-Fernández, Beatriz; Gredilla, Ricardo

    According with different international organizations, cardiovascular diseases are becoming the first cause of death in western countries. Although exposure to different risk factors, particularly those related to lifestyle, contribute to the etiopathogenesis of cardiac disorders, the increase in average lifespan and aging are considered major determinants of cardiac diseases events. Mitochondria and oxidative stress have been pointed out as relevant factors both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy and diabetic cardiomyopathy. During aging, cellular processes related with mitochondrial function, such as bioenergetics, apoptosis and inflammation are altered leading to cardiac dysfunction. Increasing our knowledge about the mitochondrial mechanisms related with the aging process, will provide new strategies in order to improve this process, particularly the cardiovascular ones. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Histologically Measured Cardiomyocyte Hypertrophy Correlates with Body Height as Strongly as with Body Mass Index

    Directory of Open Access Journals (Sweden)

    Richard E. Tracy

    2011-01-01

    Full Text Available Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH. This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height2.7 as a proxy for lean body mass and body mass index (BMI as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

  1. The Role of PDH Inhibition in the Development of Hypertrophy in the Hyperthyroid Rat Heart: A Combined MRI and Hyperpolarized MRS Study

    Science.gov (United States)

    Atherton, Helen J.; Dodd, Michael S.; Heather, Lisa C.; Schroeder, Marie A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Tyler, Damian J.

    2015-01-01

    Background Hyperthyroidism increases heart rate, contractility and cardiac output, as well as metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate utilisation. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase (PDK), thereby inhibiting glucose oxidation via pyruvate dehydrogenase (PDH). Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy (MRS) to investigate the rate and regulation of in vivo pyruvate dehydrogenase (PDH) flux in the hyperthyroid heart, and to establish whether modulation of flux through PDH would alter cardiac hypertrophy. Methods & Results Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (T3; 0.2 mg/kg/day). In vivo PDH flux, assessed using hyperpolarized MRS, was reduced by 59% in hyperthyroid animals (0.0022 ± 0.0002 s−1 vs 0.0055 ± 0.0005 s−1, P = 0.0003) and this reduction was completely reversed by both acute and chronic delivery of the PDK inhibitor, dichloroacetic acid (DCA). Hyperpolarized [2-13C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine MRI showed that chronic DCA treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100 ± 20 mg vs 200 ± 30 mg; P = 0.04) despite no change to the increase observed in cardiac output. Conclusions This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is PDK mediated. Relieving this inhibition can increase the metabolic flexibility of the hyperthyroid heart and reduce the level of hypertrophy that develops

  2. Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study.

    Science.gov (United States)

    Atherton, Helen J; Dodd, Michael S; Heather, Lisa C; Schroeder, Marie A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Tyler, Damian J

    2011-06-07

    Hyperthyroidism increases heart rate, contractility, cardiac output, and metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate use. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase, thereby inhibiting glucose oxidation via pyruvate dehydrogenase. Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy to investigate the rate and regulation of in vivo pyruvate dehydrogenase flux in the hyperthyroid heart and to establish whether modulation of flux through pyruvate dehydrogenase would alter cardiac hypertrophy. Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (0.2 mg x kg(-1) x d(-1)). In vivo pyruvate dehydrogenase flux, assessed with hyperpolarized magnetic resonance spectroscopy, was reduced by 59% in hyperthyroid animals (0.0022 ± 0.0002 versus 0.0055 ± 0.0005 second(-1); P=0.0003), and this reduction was completely reversed by both short- and long-term delivery of dichloroacetic acid, a pyruvate dehydrogenase kinase inhibitor. Hyperpolarized [2-(13)C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine magnetic resonance imaging showed that long-term dichloroacetic acid treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100 ± 20 versus 200 ± 30 mg; P=0.04) despite no change in the increase observed in cardiac output. This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is mediated by pyruvate dehydrogenase kinase. Relieving this inhibition can increase the metabolic

  3. Core competencies for cardiac rehabilitation/secondary prevention professionals: 2010 update: position statement of the American Association of Cardiovascular and Pulmonary Rehabilitation.

    Science.gov (United States)

    Hamm, Larry F; Sanderson, Bonnie K; Ades, Philip A; Berra, Kathy; Kaminsky, Leonard A; Roitman, Jeffrey L; Williams, Mark A

    2011-01-01

    Cardiac rehabilitation/secondary prevention (CR/SP) services are typically delivered by a multidisciplinary team of health care professionals. The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) recognizes that to provide high-quality services, it is important for these health care professionals to possess certain core competencies. This update to the previous statement identifies 10 areas of core competencies for CR/SP health care professionals and identifies specific knowledge and skills for each core competency. These core competency areas are consistent with the current list of core components for CR/SP programs published by the AACVPR and the American Heart Association and include comprehensive cardiovascular patient assessment; management of blood pressure, lipids, diabetes, tobacco cessation, weight, and psychological issues; exercise training; and counseling for psychosocial, nutritional, and physical activity issues.

  4. Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

    Science.gov (United States)

    Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2015-07-01

    Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Isolated unilateral temporalis muscle hypertrophy in a child: a case report with literature review

    OpenAIRE

    Ranasinghe, Jagath C.; Wickramasinghe, Chandani; Rodrigo, Ganganath

    2018-01-01

    Background Temporalis muscle hypertrophy is a rare entity of masticatory muscle hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis muscle hypertrophy is one. Temporalis muscle hypertrophy is most commonly bilateral and usually associated with other types of masticatory muscles hypertrophy such as masseter or pterygoid hypertrophy. However, isolated unilateral temporalis muscle hypertrophy is extremely rare and only 9 cases have been reported to...

  6. Ugly duckling or Nosferatu? Cardiac injury in endurance sport - screening recommendations.

    Science.gov (United States)

    Leischik, R; Dworrak, B

    2014-01-01

    In the beginning sporting activity may be exhausting, but over time, physical activity turns out to have beneficial effects to the body and even extended cycling or running is an emotional and healthy enrichment in life. On the other hand, spectacular sudden deaths during marathon, football and, just recently, in the trend discipline triathlon seem to support the dark side of the sporting activity. Since years there are constantly appearing reports about a potential myocardial injury induced by intensive sporting activities. Cardiac hypertrophy is the heart's response to arterial hypertension and to physical activity, but can be associated with an unfavorable outcome - in worst case for example with sudden death. The question of the right dose of sporting activity, the question how to prevent cardiac death induced by physical activity and the question how to screen the athletes for the possible risk of sudden death or other cardiac complications during sporting activity are those that will be answered by this review article. In this review we summarize recent insights into the problem of endurance sport and possible negative cardiac remodeling as well as the question how to screen the athletes.

  7. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

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    Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

    2015-08-15

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  8. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    International Nuclear Information System (INIS)

    Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

    2015-01-01

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m 2 for women or ≥ 116 g/m 2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m 2 (± 28.5; 99.2 to 228.5 g/m 2 ] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  9. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Directory of Open Access Journals (Sweden)

    Ana Baptista

    2015-01-01

    Full Text Available Abstract Background: Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. Objective: To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. Methods: The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. Results: A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%. Nine (19.1% showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5, a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. Conclusion: In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5.

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

    Directory of Open Access Journals (Sweden)

    Yanli Zhao

    Full Text Available Heme oxygenase-1 (HO-1 has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM. In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1 or mutant HO-1 (Tg-mutHO-1. The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt and AMP-activated protein kinase (AMPK phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.

  11. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    Science.gov (United States)

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

    2016-01-01

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

  12. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

    Directory of Open Access Journals (Sweden)

    Sujith Dassanayaka

    2018-07-01

    Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

  13. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Neeraj Parakh

    2015-01-01

    Full Text Available Sudden cardiac death is one of the most common cause of mortality worldwide. Despite significant advances in the medical science, there is little improvement in the sudden cardiac death related mortality. Coronary artery disease is the most common etiology behind sudden cardiac death, in the above 40 years population. Even in the apparently healthy population, there is a small percentage of patients dying from sudden cardiac death. Given the large denominator, this small percentage contributes to the largest burden of sudden cardiac death. Identification of this at risk group among the apparently healthy individual is a great challenge for the medical fraternity. This article looks into the causes and methods of preventing SCD and at some of the Indian data. Details of Brugada syndrome, Long QT syndrome, Genetics of SCD are discussed. Recent guidelines on many of these causes are summarised.

  14. [A girl with congenital hemifacial hypertrophy

    NARCIS (Netherlands)

    Broeke, S.M. van den; Wolvius, E.B.; Adrichem, L.N. van; Baat, C. de

    2006-01-01

    A girl with congenital hemifacial hypertrophy had been observed and treated by a multidisciplinary team for craniofacial disorders in an academic medical centre since birth. At the age of 8 she was treated on account of considerable facial asymmetry and multiple intraoral problems. The two-step

  15. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there

  16. Left ventricular hypertrophy: virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, Saraswati; Sharma, Umesh C.; Pinto, Yigal M.

    2003-01-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there

  17. Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts

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    Alexandre Lewalle

    2018-02-01

    Full Text Available The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks. Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%, rather than on anatomical features (average decrease ~60%, to achieve compensation of pump function in the early phase of heart failure.

  18. Prophylactic levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease.

    Science.gov (United States)

    Hummel, Johanna; Rücker, Gerta; Stiller, Brigitte

    2017-08-02

    Low cardiac output syndrome remains a serious complication, and accounts for substantial morbidity and mortality in the postoperative course of paediatric patients undergoing surgery for congenital heart disease. Standard prophylactic and therapeutic strategies for low cardiac output syndrome are based mainly on catecholamines, which are effective drugs, but have considerable side effects. Levosimendan, a calcium sensitiser, enhances the myocardial function by generating more energy-efficient myocardial contractility than achieved via adrenergic stimulation with catecholamines. Thus potentially, levosimendan is a beneficial alternative to standard medication for the prevention of low cardiac output syndrome in paediatric patients after open heart surgery. To review the efficacy and safety of the postoperative prophylactic use of levosimendan for the prevention of low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. We identified trials via systematic searches of CENTRAL, MEDLINE, Embase, and Web of Science, as well as clinical trial registries, in June 2016. Reference lists from primary studies and review articles were checked for additional references. We only included randomised controlled trials (RCT) in our analysis that compared prophylactic levosimendan with standard medication or placebo, in infants and children up to 18 years of age, who were undergoing surgery for congenital heart disease. Two review authors independently extracted data and assessed risk of bias according to a pre-defined protocol. We obtained additional information from all but one of the study authors of the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence from the studies that contributed data to the meta-analyses for the prespecified outcomes. We created a 'Summary of findings' table to

  19. A Multifactorial Intervention Based on the NICE-Adjusted Guideline in the Prevention of Delirium in Patients Hospitalized for Cardiac Surgery

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    Mohammad Ali Cheraghi

    2017-05-01

    Full Text Available Delirium is the most common problem in patients in intensive care units. Prevention of delirium is more important than treatment. The aim of this study is to determine the effect of the NICE-adjusted multifactorial intervention to prevent delirium in open heart surgery patients. Methods: This study is a quasi-experimental study on 88 patients (In each group, 44 patients undergoing open heart surgery in the intensive care unit of Imam Khomeini Hospital, Tehran. Subjects received usual care group, only the incidence of delirium were studied. So that patients in the two groups of second to fifth postoperative day, twice a day by the researcher, and CAM-ICU questionnaire were followed. After completion of the sampling in this group, in the intervention group also examined incidence of delirium was conducted in the same manner except that multifactorial interventions based on the intervention of NICE modified by the researcher on the second day to fifth implementation and intervention on each turn, their implementation was followed. As well as to check the quality of sleep and pain in the intervention group of CPOT and Pittsburgh Sleep assessment tools were used. Data analysis was done using the SPSS software, version 16. A T-test, a chi-square test, and a Fisher’s exact test were also carried out. Results: The incidence of delirium in the control group was 42.5%; and in the intervention group, it was 22.5%. The result showed the incidence of delirium in open heart surgery hospitalized patients after multifactorial intervention based on adjusted NICE guidelines has been significantly reduced. Conclusion: The NICE-adjusted multifactorial intervention guidelines for the prevention of delirium in cardiac surgery patients significantly reduced the incidence of delirium in these patients. So, using this method as an alternative comprehensive and reliable in preventing delirium in hospitalized patients in the ward heart surgery is recommended.

  20. Impact of left ventricular end diastolic pressure guided hydration on prevention of contrast induced nephropathy post cardiac catheterization

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    Sherif Wagdy Ayad

    2015-12-01

    Conclusions: LVEDP-guided hydration is superior to standard hydration in prevention of CIN. Hydration can be done based on LVFP in patients with pre-procedure normal LVF and in patients with pre-procedure elevated LVFP but not in those patients with inconclusive LVFP in which hydration should be guided by the invasively measured LVEDP.

  1. Applying preoperative dipyridamole thallium-201 scintigraphy for preventing cardiac mortality and complications for patients with secondary hyperparathyroidism undergoing parathyroidectomy

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    Shih-min Yin

    2018-05-01

    Full Text Available Summary: Background: To evaluate the value of preoperative dipyridamole thallium-201 scintigraphy for reducing cardiovascular complication in secondary hyperparathyroidism (SHPTH patients. Methods: Thallium scintigraphy was arranged for all dialysis patients who underwent parathyroidectomy from Jan 2011 to July 2015. Management of defects on thallium scintigraphy included cardiac catheterization and ultrasonography. Analysis includes 30-day mortality, morbidity and the predicting factors for thallium scintigraphy defect. Results: Of 249 patients with SHPTH, 19 (7.6% had defects on thallium scintigraphy, 15 (88% of whom had coronary artery disease on angiography. History of acute coronary syndrome (ACS, p < 0.001, diabetes mellitus (DM, p = 0.03, male sex (p = 0.03, and higher body mass index (BMI, p = 0.001 were significant predictors of positive thallium scintigraphy results. History of ACS was the most significant predictor after adjustment in the multivariate logistic analysis (odds ratio, 22.56; 95% confidence interval, 7.02–72.53. All the patients survived the 30-day postoperative period, with minimal cardiovascular morbidity. Conclusion: Preoperative dipyridamole thallium-201 scintigraphy is useful for SHPTH patients to minimized surgical mortality and morbidity. Keywords: Secondary hyperparathyroidism, Dialysis, Coronary artery disease (CAD, Dipyridamole thallium-201 scintigraphy

  2. Usefulness of Sodium Bicarbonate for the Prevention of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Alonso, Pau; Sanz, Jorge; García-Orts, Ana; Reina, Samuel; Jiménez, Sonia; Osca, Joaquín; Cano, Oscar; Andrés, Ana; Sancho-Tello, María José; Martínez, Luis

    2017-11-01

    The use of contrast media during cardiac resynchronization therapy (CRT) devices implantation is associated with the risk of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the possible beneficial role of periprocedural intravenous volume expansion with isotonic saline and sodium bicarbonate solution in patients who undergo CRT implantation. Eligible patients were randomly assigned in a 1:1 ratio to receive hydration plus one-sixth molar sodium bicarbonate (study group) or not (control group). Primary end point was CIN incidence. Secondary end points were (1) a combined end point of death, heart transplantation, or hospitalization for heart failure at 12 months, (2) incidence of death, and (3) the need for renal replacement therapy at 12 months. Final analysis was performed with 93 patients. In the hydration group CIN incidence was significantly reduced related to control group (0% vs 11%, p = 0.02). There was a trend to reduce the combined end point in hydration group (12.5% vs 22%, p = 0.14). Finally, CIN incidence was related to a higher 12 months mortality (25% vs 7%, p = 0.03). In conclusion, CIN incidence was 11% in a nonselected population of patients receiving a CRT device. CIN appearance could be reduced by using a hydration protocol based on sodium bicarbonate and isotonic saline. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

  4. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

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    Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

    2003-09-01

    The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

  5. HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Huang, Chih-Yang; Lee, Fa-Lun; Peng, Shu-Fen; Lin, Kuan-Ho; Chen, Ray-Jade; Ho, Tsung-Jung; Tsai, Fu-Jen; Padma, Vijaya V; Kuo, Wei-Wen; Huang, Chih-Yang

    2018-02-01

    Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT 1 R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 S303 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients. © 2017 Wiley Periodicals, Inc.

  6. Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events.

    Science.gov (United States)

    Schnell-Inderst, Petra; Schwarzer, Ruth; Göhler, Alexander; Grandi, Norma; Grabein, Kristin; Stollenwerk, Björn; Klauß, Volker; Wasem, Jürgen; Siebert, Uwe

    2009-05-12

    In a substantial portion of patients (= 25%) with coronary heart disease (CHD), a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP) in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-fatal myocardial infarction. Does the additional information gained through the measurement of hs-CRP in asymptomatic patients lead to a clinically relevant improvement in risk prediction as compared to risk prediction based on traditional risk factors and is this cost-effective? A literature search of the electronic databases of the German Institute of Medical Documentation and Information (DIMDI) was conducted. Selection, data extraction, assessment of the study-quality and synthesis of information was conducted according to the methods of evidence-based medicine. Eight publications about predictive value, one publication on the clinical efficacy and three health-economic evaluations were included. In the seven study populations of the prediction studies, elevated CRP-levels were almost always associated with a higher risk of cardiovascular events and non-fatal myocardial infarctions or cardiac death and severe cardiovascular events. The effect estimates (odds ratio (OR), relative risk (RR), hazard ratio (HR)), once adjusted for traditional risk factors, demonstrated a moderate, independent association between hs-CRP and cardiac and cardiovascular events that fell in the range of 0.7 to 2.47. In six of the seven studies, a moderate increase in the area under the curve (AUC) could be detected by adding hs-CRP as a predictor to regression models in addition to established risk factors though in three cases this was not statistically significant. The difference [in the AUC] between the

  7. Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events

    Directory of Open Access Journals (Sweden)

    Klauß, Volker

    2009-05-01

    Full Text Available Background: In a substantial portion of patients (= 25% with coronary heart disease (CHD, a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-fatal myocardial infarction. Research question: Does the additional information gained through the measurement of hs-CRP in asymptomatic patients lead to a clinically relevant improvement in risk prediction as compared to risk prediction based on traditional risk factors and is this cost-effective? Methods: A literature search of the electronic databases of the German Institute of Medical Documentation and Information (DIMDI was conducted. Selection, data extraction, assessment of the study-quality and synthesis of information was conducted according to the methods of evidence-based medicine. Results: Eight publications about predictive value, one publication on the clinical efficacy and three health-economic evaluations were included. In the seven study populations of the prediction studies, elevated CRP-levels were almost always associated with a higher risk of cardiovascular events and non-fatal myocardial infarctions or cardiac death and severe cardiovascular events. The effect estimates (odds ratio (OR, relative risk (RR, hazard ratio (HR, once adjusted for traditional risk factors, demonstrated a moderate, independent association between hs-CRP and cardiac and cardiovascular events that fell in the range of 0.7 to 2.47. In six of the seven studies, a moderate increase in the area under the curve (AUC could be detected by adding hs-CRP as a predictor to regression models in addition to established risk factors though in three cases this was not

  8. [Role of cardiac magnetic resonance in cardiac involvement of Fabry disease].

    Science.gov (United States)

    Serra, Viviana M; Barba, Miguel Angel; Torrá, Roser; Pérez De Isla, Leopoldo; López, Mónica; Calli, Andrea; Feltes, Gisela; Torras, Joan; Valverde, Victor; Zamorano, José L

    2010-09-04

    Fabry disease is a hereditary disorder. Clinical manifestations are multisystemic. The majority of the patients remain undiagnosed until late in life, when alterations could be irreversible. Early detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD. This study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD. Echocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease. Left ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12 mm. An abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities gadolinium-enhanced images sequences were obtained using magnetic resonance. Twenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment. Late gadolinium enhancement was found in only one patient, who has already altered DTI and LVH. Tissue Doppler imaging (TDI) is the only diagnostic tool able to provide early detection of cardiac affectation in patients with FD. Magnetic resonance provides information of the disease severity in patients with LVH, but can not be used as an early marker of cardiac disease in patients with FD. However MRI could be of great value for diagnostic stratification. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  9. Cardiac Diastolic Evaluation in Pregnant Women with Abnormal Glucose Tolerance: An Opportunity to Detect the Early and Subclinical Alterations and Prevent Cardiovascular Diseases

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    B. Pintaudi

    2013-01-01

    Full Text Available Objectives of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT, compared with normal glucose tolerance (NGT women, and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes. Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performed. Insulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR and the quantitative insulin sensitivity check index (QUICKI. All the studied women showed normal diastolic patterns. Patients with AGT (50.9%, as compared with NGT women, had higher HOMA-IR (1.70±1.30 versus 1.01±0.81, P=0.003, lower QUICKI (0.36±0.005 versus 0.40±0.06, P=0.004, higher lateral mitral annulus late diastolic velocity (13.6±4.9 versus 11.9±4.9, P=0.03, and higher A-wave velocity, the wave responsible for the active atrial contraction component (75.2±14.2 versus 67.7±16.2, P=0.01. At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity. In conclusion, women with AGT had an increased subclinical diastolic active participation, which is associated with higher levels of insulin resistance. For the increased risk of deterioration of cardiac diastolic function, earlier and more seriously than normal pregnancy, AGT women may have a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases.

  10. The soluble guanylyl cyclase activator bay 58-2667 selectively limits cardiomyocyte hypertrophy.

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    Jennifer C Irvine

    Full Text Available Although evidence now suggests cGMP is a negative regulator of cardiac hypertrophy, the direct consequences of the soluble guanylyl cyclase (sGC activator BAY 58-2667 on cardiac remodeling, independent of changes in hemodynamic load, has not been investigated. In the present study, we tested the hypothesis that the NO(•-independent sGC activator BAY 58-2667 inhibits cardiomyocyte hypertrophy in vitro. Concomitant impact of BAY 58-2667 on cardiac fibroblast proliferation, and insights into potential mechanisms of action, were also sought. Results were compared to the sGC stimulator BAY 41-2272.Neonatal rat cardiomyocytes were incubated with endothelin-1 (ET(1, 60nmol/L in the presence and absence of BAY 41-2272 and BAY 58-2667 (0.01-0.3 µmol/L. Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. The impact of both sGC ligands on basal and stimulated cardiac fibroblast proliferation in vitro was also determined.We now demonstrate that BAY 58-2667 (0.01-0.3 µmol/L elicited concentration-dependent antihypertrophic actions, inhibiting ET(1-mediated increases in cardiomyocyte 2D area and de novo protein synthesis, as well as suppressing ET(1-induced cardiomyocyte superoxide generation. This was accompanied by potent increases in cardiomyocyte cGMP accumulation and activity of its downstream signal, vasodilator-stimulated phosphoprotein (VASP, without elevating cardiomyocyte cAMP. In contrast, submicromolar concentrations of BAY 58-2667 had no effect on basal or stimulated cardiac fibroblast proliferation. Indeed, only at concentrations ≥10 µmol/L was inhibition of cardiac fibrosis seen in vitro. The effects of BAY 58-2667 in both cell types were mimicked by BAY 41-2272.Our results demonstrate that BAY 58-2667 elicits protective, cardiomyocyte-selective effects in vitro. These actions are associated with sGC activation and are evident in the absence of confounding hemodynamic factors, at low (submicromolar

  11. Prevention of Cardiac Implantable Electronic Device Infections: Single Operator Technique with Use of Povidone-Iodine, Double Gloving, Meticulous Aseptic/Antiseptic Measures and Antibiotic Prophylaxis.

    Science.gov (United States)

    Manolis, Antonis S; Melita, Helen

    2017-01-01

    Cardiac implantable electronic device (CIED) implantation is complicated by infection still at a worrisome rate of 2-5%. Since early on during device implantation procedures, we have adopted an infection-preventive technique which has hitherto resulted in effective prevention of infections. Herein we present our results of applying this technique by a single operator in a prospective series of 762 consecutive patients undergoing device implantation. A meticulous search for and treatment of active, occult, or smoldering infection was undertaken preoperatively. An aseptic/antiseptic technique was used for implantation of each device. Skin preparation is thorough with initial cleansing performed with alcohol followed by povidone-iodine 10% solution, which is also used in the wound and inside the pocket. In addition, we routinely use double gloving, and IV antibiotic prophylaxis 1 hour before and for 48 hours afterwards followed by oral antibiotic for 2-3 days after discharge. The skin is closed with absorbable sutures. The study includes 382 patients having a new pacemaker (n = 333) or battery change, system upgrade or lead revision (n = 49), and 380 patients having a new implantable cardioverter-defibrillator (ICD) (n = 296) or device replacement/upgrade/lead revision (n = 84). The pacemaker group, aged 70.2 ± 16.5 years, includes 18% VVI, 49% DDD, 29% VDD, and 4% cardiac resynchronization therapy (CRT) devices. The ICD group, aged 61.3 ± 13.0 years, with a mean ejection fraction of 36 ± 13%, includes 325 ICD and 55 CRT implants. Over 26.6 ± 33.4 months for the pacemaker group and 36.6 ± 38.3 months for the ICD group, infection occurred in one patient in each group (0.26%) having a device replacement. A consistent and strict approach of aseptic/antiseptic technique with the use of double gloving and povidone-iodine solution within the pocket plus a 4-day regimen of antibiotic prophylaxis minimizes infections in CIED implants. © 2016 Wiley Periodicals, Inc.

  12. Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity.

    Science.gov (United States)

    Martínez-Martínez, Ernesto; Jurado-López, Raquel; Valero-Muñoz, María; Bartolomé, María Visitación; Ballesteros, Sandra; Luaces, María; Briones, Ana María; López-Andrés, Natalia; Miana, María; Cachofeiro, Victoria

    2014-05-01

    Leptin acts as a cardiac profibrotic factor. However, the mechanisms underlying this effect are unclear. Therefore, we sought to elucidate the mediators involved in this process and the potential role of leptin in cardiac fibrosis associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 33.5% fat), or a standard diet (3.5% fat) for 6 weeks. HFD animals show cardiac hypertrophy, fibrosis and an increase in O2- production as evaluated by dihydroethidium. Echocardiographic parameters of cardiac structure and systolic function were similar in both groups. Cardiac levels of leptin, collagen I, galectin-3 and transforming growth factor β (TGF-β) were higher in HFD than in controls. In cardiac myofibroblasts, leptin (10-100 ng/ml) increased O2-, collagen I, galectin-3, TGF-β and connective tissue growth factor production (CTGF). These effects were prevented by the presence of either melatonin (10 mmol/l) or the inhibitor of mTOR, rapamycin (10 mmol/l). Blockage of galectin-3 activity by N-acetyllactosamine (LacNac 10 mmol/l) reduced both collagen I and O2(*-) production induced by leptin. The p70S6 kinase activation/phosphorylation, the downstream mediator of mTOR, induced by leptin was not modified by melatonin. Leptin reduced the metalloproteinase (MMP) 2 activity and the presence of melatonin, rapamycin or LacNac were unable to prevent it. The data suggest that leptin locally produced in the heart could participate in the fibrosis observed in HFD by affecting collagen turnover. Collagen synthesis induced by leptin seems to be mediated by the production of galectin-3, TGF-β and CTGF through oxidative stress increased by activation of mTOR pathway.

  13. Left ventricular hypertrophy: virtuous intentions, malign consequences.

    Science.gov (United States)

    Pokharel, Saraswati; Sharma, Umesh C; Pinto, Yigal M

    2003-06-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there are structural changes in myofilaments, disorganization of the cytoskeletal framework and increased collagen synthesis. LVH is associated with progressive left ventricular remodeling that culminates to heart failure. The modern treatment of left ventricular hypertrophy is now largely based on the hypothesis that neuroendocrine activation is important in the progression of the disease and inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Drugs specifically designed to unload the left ventricle, such as diuretics and vasodilators, appears to be less effective in reducing LV mass and improving prognosis. Thus, the evolution of treatment for LVH itself has provided much enlightenment for our understanding of the fundamental biology of the disorder.

  14. Cardiac rehabilitation

    Science.gov (United States)

    ... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  15. Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery: a policy statement from the cardiac rehabilitation section of the European Association for Cardiovascular Prevention & Rehabilitation. Endorsed by the Committee for Practice Guidelines of the European Society of Cardiology.

    Science.gov (United States)

    Piepoli, Massimo F; Corrà, Ugo; Adamopoulos, Stamatis; Benzer, Werner; Bjarnason-Wehrens, Birna; Cupples, Margaret; Dendale, Paul; Doherty, Patrick; Gaita, Dan; Höfer, Stefan; McGee, Hannah; Mendes, Miguel; Niebauer, Josef; Pogosova, Nana; Garcia-Porrero, Esteban; Rauch, Bernhard; Schmid, Jean Paul; Giannuzzi, Pantaleo

    2014-06-01

    Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice. © The European Society of Cardiology 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Left Ventricular Hypertrophy in Pediatric Hypertension: A Mini Review

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    Robert P. Woroniecki

    2017-05-01

    Full Text Available Adults with arterial hypertension (HTN have stroke, myocardial infarction, end-stage renal disease (ESRD, or die at higher rates than those without. In children, HTN leads to target organ damage, which includes kidney, brain, eye, blood vessels, and heart, which precedes “hard outcomes” observed in adults. Left ventricular hypertrophy (LVH or an anatomic and pathologic increase in left ventricular mass (LVM in response to the HTN is a pediatric surrogate marker for HTN-induced morbidity and mortality in adults. This mini review discusses current definitions, clinically relevant methods of LVM measurements and normalization methods, its epidemiology, management, and issue of reversibility in children with HTN. Pediatric definition of LVH and abnormal LVM is not uniformed. With multiple definitions, prevalence of pediatric HTN-induced LVH is difficult to ascertain. In addition while in adults cardiac magnetic resonance imaging is considered “the gold standard” for LVM and LVH determination, pediatric data are limited to “special populations”: ESRD, transplant, and obese children. We summarize available data on pediatric LVH treatment and reversibility and offer future directions in addressing LVH in children with HTN.

  17. Non-gated computed tomography of left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Harada, Junta

    1983-01-01

    Non-ECG gated computed tomography (CT) of the heart was carried out in 19 cases with cardiovascular diseases; 4 with mitral stenosis, 3 with aortic valve disease, 2 with combined valve disease, 8 with hypertrophic cardiomyopathy and one myocardial infarction and one aortic aneurysm. All cardiac diseases were studied by echocardiography and 13 of them further investigated by intracadiac catheterization. The interventricular septum and the apical and posterolateral wall of the left ventricle were segmentally evaluated as to relative wall thickness of myocardium on CT. The wall thickness was directly measured on left ventricular cine angiograms in 13 cases. O-G vector calculated by CT was compatible with the palne of vectorcardiography in evaluating left ventricular hypertorphy. Conclusion were as follows: 1) The degree and site of myocardial hypertrophy were detected by CT with satisfaction. 2) The area of ventricular myocardium increased in aortic valve disease and hypertrophic cardiomyopathy. 3) The direction and magnitude of O-G vector calculated by CT were well correlated to the half area of QRS loop in horizontal plane of vectorcardiography. (author)

  18. Relationship between obesity and left ventricular hypertrophy in children

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    Johnny Rompis

    2016-10-01

    Full Text Available Background Obesity is a chronic metabolic disorder associated with cardiovascular disease (CVD increasing morbidity-mortality rates. It is apparent that a variety of adaptations/alterations in cardiac structure and function occurs as excessive adipose tissue accumulates. This leads to a decrease in diastolic compliance, eventually resulting in an increase in left ventricular filling pressure and left ventricular enlargement. Objective To evaluate left ventricular hypertrophy (LVH among  obese using electrocardiographic (ECG criteria. Methods A cross-sectional study was conducted on 74 children aged 10-15 years from February 2009 to October 2009. The subjects were divided into obese and control groups. Physical examination and standard 12 lead electrocardiography (ECG were done in both groups. Results Of 37 obese children, LVH were featured in 3 subjects, while in control group, only 1 child had LVH (P= 0.304. We found that mean RV6 in obese and control group were 9.8446 (SD 3.5854 and 11.9662 (SD 3.2857, respectively (P=0.005. As an additional findings, we found that birth weight was related to obesity in children. Conclusion There is no relation between obesity and left ventricular using ECG criteria in obese children aged 10-15 years.

  19. Breast Hypertrophy, Reduction Mammaplasty, and Body Image.

    Science.gov (United States)

    Fonseca, Cristiane Costa; Veiga, Daniela Francescato; Garcia, Edgard da Silva; Cabral, Isaías Vieira; de Carvalho, Monique Maçais; de Brito, Maria José Azevedo; Ferreira, Lydia Masako

    2018-02-07

    Body image dissatisfaction is one of the major factors that motivate patients to undergo plastic surgery. However, few studies have associated body satisfaction with reduction mammaplasty. The aim of this study was to evaluate the impact of breast hypertrophy and reduction mammaplasty on body image. Breast hypertrophy patients, with reduction mammaplasty already scheduled between June 2013 and December 2015 (mammaplasty group, MG), were prospectively evaluated through the body dysmorphic disorder examination (BDDE), body investment scale (BIS), and breast evaluation questionnaire (BEQ55) tools. Women with normal-sized breasts were also evaluated as study controls (normal-sized breast group, NSBG). All the participants were interviewed at the initial assessment and after six months. Data were analyzed before and after six months. Each group consisted of 103 women. The MG group had a significant improvement in BDDE, BIS, and BEQ55 scores six months postoperatively (P ≤ 0.001 for the three instruments), whereas the NSBG group showed no alteration in results over time (P = 0.876; P = 0.442; and P = 0.184, respectively). In the intergroup comparison it was observed that the MG group began to invest more in the body, similarly to the NSBG group, and surpassed the level of satisfaction and body image that the women of the NSBG group had after the surgery. Reduction mammaplasty promoted improvement in body image of women with breast hypertrophy. © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  20. Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

    Science.gov (United States)

    Belmonte, Stephen L; Ram, Rashmi; Mickelsen, Deanne M; Gertler, Frank B; Blaxall, Burns C

    2013-09-15

    Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

  1. Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation: The Role of Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Xia Yin

    2012-01-01

    Full Text Available Obstructive sleep apnea (OSA is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH. Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy to decompensating changes (such as failure. CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

  2. Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

    International Nuclear Information System (INIS)

    Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C.

    1990-01-01

    Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 ± 1.8 to 28.1 ± 6.8 (NS) at 3-day postirradiation, 37.7 ± 1.9 (P less than .001) at 6-day postirradiation, and 43.8 ± 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity

  3. Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

    Science.gov (United States)

    Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

    2018-04-20

    To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

  4. Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Hyun Kang

    Full Text Available We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model.A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25 and saline as the control group (group CO; n = 25. In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery.In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001. Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002 and fibrosis score (P = .018 than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant.In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

  5. Validation of the 2014 European Society of Cardiology guidelines risk prediction model for the primary prevention of sudden cardiac death in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Vriesendorp, Pieter A; Schinkel, Arend F L; Liebregts, Max; Theuns, Dominic A M J; van Cleemput, Johan; Ten Cate, Folkert J; Willems, Rik; Michels, Michelle

    2015-08-01

    The recently released 2014 European Society of Cardiology guidelines of hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is the first external and independent validation of this new risk prediction model. The study population consisted of a consecutive cohort of 706 patients with HCM without prior SCD event, from 2 tertiary referral centers. The primary end point was a composite of SCD and appropriate implantable cardioverter-defibrillator therapy, identical to the HCM Risk-SCD end point. The 5-year SCD risk was calculated using the HCM Risk-SCD formula. Receiver operating characteristic curves and C-statistics were calculated for the 2014 European Society of Cardiology guidelines, and risk stratification methods of the 2003 American College of Cardiology/European Society of Cardiology guidelines and 2011 American College of Cardiology Foundation/American Heart Association guidelines. During follow-up of 7.7±5.3 years, SCD occurred in 42 (5.9%) of 706 patients (ages 49±16 years; 34% women). The C-statistic of the new model was 0.69 (95% CI, 0.57-0.82; P=0.008), which performed significantly better than the conventional risk factor models based on the 2003 guidelines (C-statistic of 0.55: 95% CI, 0.47-0.63; P=0.3), and 2011 guidelines (C-statistic of 0.60: 95% CI, 0.50-0.70; P=0.07). The HCM Risk-SCD model improves the risk stratification of patients with HCM for primary prevention of SCD, and calculating an individual risk estimate contributes to the clinical decision-making process. Improved risk stratification is important for the decision making before implantable cardioverter-defibrillator implantation for the primary prevention of SCD. © 2015 American Heart Association, Inc.

  6. Protection of MICU1 against myocardial hypertrophy induced by angiotensin Ⅱ

    Directory of Open Access Journals (Sweden)

    Yi YANG

    2017-12-01

    Full Text Available Objective To investigate the role of mitochondrial calcium uptake 1 (MICU1 in myocardial hypertrophy of mice and underlying mechanism. Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM with 300nmol/L angiotensin Ⅱ (Ang Ⅱ for 48 hours in vitro. After that, MICU1 specific small interfering RNA (siRNA was delivered to knockdown MICU1 levels in MCM. On the other hand, adenovirus-mediated over-expression of MICU1 was transfected into MCM. Accordingly, the expressions of ANP and BNP in myocardial cells were measured by qRT- PCR. Mitochondrial membrane potential and ATP contents were detected by JC-1 assay kit and ATP assay kit, respectively. Then, Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells. The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy. The size of myocardial cells was determined by α-actinin staining. Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by AngⅡ were both decreased. Meanwhile, myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels. With the method of genetic intervention, we found that MICU1 deficiency exacerbated mitochondrial Ca2+ overload, increased cell surface and elevated the expression of BNP. Conversely, the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload, cell surface of MCM and expressions of ANP and BNP. Conclusion MICU1 alleviates AngⅡ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload. DOI: 10.11855/j.issn.0577-7402.2017.12.05

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  8. Patients with FGF23-related hypophosphatemic rickets/osteomalacia do not present with left ventricular hypertrophy.

    Science.gov (United States)

    Takashi, Yuichi; Kinoshita, Yuka; Hori, Michiko; Ito, Nobuaki; Taguchi, Manabu; Fukumoto, Seiji

    2017-05-01

    Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate metabolism. Excessive actions of FGF23 cause several types of FGF23-related hypophosphatemic rickets/osteomalacia. Recently, it was reported that FGF23 levels were independently correlated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). In addition, FGF23 was also shown to cause cardiac hypertrophy directly acting on cardiomyocytes. However, there is no study indicating the correlation between FGF23 and LVH in adult patients with FGF23-related hypophosphatemic rickets/osteomalacia. Therefore, we examined the existence of LVH in these patients. We recruited consecutive 24 patients with FGF23-related hypophosphatemic diseases. Their serum intact FGF23 levels and the parameters associated with LVH, including left ventricular mass index (LVMI), relative wall thickness (RWT), Sokolow-Lyon voltage, and Cornell product, were measured. The correlations between FGF23 and these parameters were examined. The participants did not show LVH on the whole. In addition, no significant correlation was observed by these examinations. It seems unlikely that FGF23 levels are the apparent determinant of the cardiac mass in patients with FGF23-related hypophosphatemic rickets/osteomalacia.

  9. Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

    OpenAIRE

    Shogo Sato; Ken Shirato; Kaoru Tachiyashiki; Kazuhiko Imaizumi

    2011-01-01

    We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented ...

  10. Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

    Directory of Open Access Journals (Sweden)

    Ali Tahir

    2015-01-01

    Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

  11. Assessment of hypertrophic cardiomyopathy by ECG gated cardiac computed tomography

    International Nuclear Information System (INIS)

    Takeuchi, Kazuhide; Tanaka, Chujiro; Oku, Hisao

    1981-01-01

    The applicability of ECG gated cardiac computed tomography (CT) in 12 patients with hypertrophic cardiomyopathy was examined. Six of the 12 patients had hypertrophic obstructive cardiomyopathy, including one patient with mid-ventricular obstruction. Three of the 12 patients had hypertrophic non-obstructive cardiomyopathy, and three had apical hypertrophic cardiomyopathy. The diagnosis of hypertrophic cardiomyopathy was confirmed by the angiocardiogram in all patients. Cardiac CT was performed after intravenous administration of contrast media usually given as a bolus injection. The gantry was set with positive 20 0 tilt angle. In all patients with hypertrophic obstructive cardiomyopathy except for mid-ventricular obstruction, the hypertrophied interventricular septum in the basal and mid portions was observed, and the left ventricular cavity was narrowed in systole. In a patient with mid-ventricular obstruction, the marked hypertrophied interventricular septum and antero-lateral papillary muscle were observed. In diastole, the left ventricular cavity was narrow and divided into two parts. The apical cavity was completely disappeared in systole. In all patients with hypertrophic non-obstructive cardiomyopathy, the diffuse hypertrophied interventricular septum was observed in diastole. In systole, the apical portion of the left ventricular cavity was markedly narrow and antero-lateral papillary muscle was hypertrophic. In all patients with apical hypertrophic cardiomyopathy, the marked apical hypertrophy of the left ventricular wall was observed in diastole. It is concluded that ECG gated cardiac CT could estimate myocardial wall motion and thickness and differentiate the types of hypertrophic cardiomyopathy each other. (author)

  12. Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

    Directory of Open Access Journals (Sweden)

    Diego Lopes Mendes Barretti

    Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

  13. Myocardial hypertrophy and intracardial hemodynamics in children with bicuspid aortic valve

    Directory of Open Access Journals (Sweden)

    А. V. Kamenshchyk

    2017-08-01

    Full Text Available Bicuspid aortic valve is one of the most common congenital heart diseases with low manifestation in childhood and severe consequences in adults that determines the importance in early diagnostics of myocardial changes in this anomaly. According to the literature the polymorphisms in the genes of NFATC family could result both in impaired embriogenetic valves formation and development of postnatal myocardial hypertrophy. The aim of the study was to detect the early changes of intracardial hemodynamics at aortic valve in children with bicuspid aortic valve (BAV and establish their interrelations to the signs of myocardial hypertrophy in these children. Materials and methods: Dopplerograhphic study of basic intracardiac hemodynamics parameters in 38 children with BAV and in 28 children of control group was conducted. The results were processed statistically by Student’s t-test, correlation analysis and multiple regression. Results: In the result of study the moderate concentric left ventricle myocardial hypertrophy development was detected in 62 % of children with BAV which is accompanying to significant increasing of blood flow velocity and pressure gradient at aortic valve. There were not established significant correlations between the parameters of hemodynamics at valve and left ventricle’s posterior wall depth and septum depth whereas the highest inputs of these values were obtained in the left ventricle systolic dimension and volume and less in the hypertrophic signs. Conclusions: In children with BAV the moderate concentric myocardial hypertrophy with significant changes of intracardial hemodynamics at aortic valve takes place with the highest inputs in left ventricle volumetric values The obtained data serves as a substantiation for the treatment and prevention of it further development. bicuspid aortic valve; children; heart hypertrophy; dopplerechocardiography; hemodynamics; regression analysis

  14. Cardiac anatomy and physiology: a review.

    Science.gov (United States)

    Gavaghan, M

    1998-04-01

    This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

  15. Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

    Science.gov (United States)

    Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

    2018-05-18

    The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

  16. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  17. Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy.

    Science.gov (United States)

    Kirby, Tyler J; Patel, Rooshil M; McClintock, Timothy S; Dupont-Versteegden, Esther E; Peterson, Charlotte A; McCarthy, John J

    2016-03-01

    Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy. © 2016 Kirby et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  18. Rivaroxaban for Preventing Atherothrombotic Events in People with Acute Coronary Syndrome and Elevated Cardiac Biomarkers: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Pandor, Abdullah; Pollard, Daniel; Chico, Tim; Henderson, Robert; Stevenson, Matt

    2016-05-01

    As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures rivaroxaban (Xarelto, Bayer) to submit evidence of the clinical and cost effectiveness of rivaroxaban for the prevention of adverse outcomes in patients after the acute management of acute coronary syndrome (ACS). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from a randomised, double-blind, phase III, placebo-controlled trial of rivaroxaban (either 2.5 or 5 mg twice daily) in patients with recent ACS [unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI)]. In addition, all patients received antiplatelet therapy [aspirin alone or aspirin and a thienopyridine either as clopidogrel (approximately 99 %) or ticlopidine (approximately 1 %) according to national or local guidelines]. The higher dose of rivaroxaban (5 mg twice daily) did not form part of the marketing authorisation. A post hoc subgroup analysis of the licensed patients who had ACS with elevated cardiac biomarkers (that is, patients with STEMI and NSTEMI) without prior stroke or transient ischaemic stroke showed that compared with standard care, the addition of rivaroxaban (2.5 mg twice daily) to existing antiplatelet therapy reduced the composite endpoint of cardiovascular mortality, myocardial infarction or stroke, but increased the risk of major bleeding and intracranial haemorrhage. However, there were a number of limitations in the evidence base that warrant caution in its interpretation. In particular, the evidence may be confounded because of the post hoc subgroup

  19. In vivo cardiac role of migfilin during experimental pressure overload.

    Science.gov (United States)

    Haubner, Bernhard Johannes; Moik, Daniel; Schuetz, Thomas; Reiner, Martin F; Voelkl, Jakob G; Streil, Katrin; Bader, Kerstin; Zhao, Lei; Scheu, Claudia; Mair, Johannes; Pachinger, Otmar; Metzler, Bernhard

    2015-06-01

    Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  20. The cardiovascular event reduction tool (CERT)--a simplified cardiac risk prediction model developed from the West of Scotland Coronary Prevention Study (WOSCOPS).

    Science.gov (United States)

    L'Italien, G; Ford, I; Norrie, J; LaPuerta, P; Ehreth, J; Jackson, J; Shepherd, J

    2000-03-15

    The clinical decision to treat hypercholesterolemia is premised on an awareness of patient risk, and cardiac risk prediction models offer a practical means of determining such risk. However, these models are based on observational cohorts where estimates of the treatment benefit are largely inferred. The West of Scotland Coronary Prevention Study (WOSCOPS) provides an opportunity to develop a risk-benefit prediction model from the actual observed primary event reduction seen in the trial. Five-year Cox model risk estimates were derived from all WOSCOPS subjects (n = 6,595 men, aged 45 to 64 years old at baseline) using factors previously shown to be predictive of definite fatal coronary heart disease or nonfatal myocardial infarction. Model risk factors included age, diastolic blood pressure, total cholesterol/ high-density lipoprotein ratio (TC/HDL), current smoking, diabetes, family history of fatal coronary heart disease, nitrate use or angina, and treatment (placebo/ 40-mg pravastatin). All risk factors were expressed as categorical variables to facilitate risk assessment. Risk estimates were incorporated into a simple, hand-held slide rule or risk tool. Risk estimates were identified for 5-year age bands (45 to 65 years), 4 categories of TC/HDL ratio ( or = 7.5), 2 levels of diastolic blood pressure ( or = 90 mm Hg), from 0 to 3 additional risk factors (current smoking, diabetes, family history of premature fatal coronary heart disease, nitrate use or angina), and pravastatin treatment. Five-year risk estimates ranged from 2% in very low-risk subjects to 61% in the very high-risk subjects. Risk reduction due to pravastatin treatment averaged 31%. Thus, the Cardiovascular Event Reduction Tool (CERT) is a risk prediction model derived from the WOSCOPS trial. Its use will help physicians identify patients who will benefit from cholesterol reduction.

  1. Alterations in rat cardiac myosin isozymes induced by whole-body irradiation are prevented by 3,5,3'-L-triiodothyronine

    Energy Technology Data Exchange (ETDEWEB)

    Litten, R.Z.; Fein, H.G.; Gainey, G.T.; Walden, T.L.; Smallridge, R.C. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-01-01

    Changes in cardiac myosin isozymes and serum thyroid hormone levels were investigated in rats following 10 Gy whole-body gamma irradiation. The percent beta-myosin heavy chain increased from 21.3 {plus minus} 1.8 to 28.1 {plus minus} 6.8 (NS) at 3-day postirradiation, 37.7 {plus minus} 1.9 (P less than .001) at 6-day postirradiation, and 43.8 {plus minus} 3.3 (P less than .001) at 9-day postirradiation. Along with the change in myosin isozymes was a significant 53% decrease (P less than .001) in the serum thyroxine (T4) level by day 3 postirradiation, remaining depressed through day 9 postirradiation. The serum 3,5,3'-triiodothyronine (T3) level, however, was normal until day 9, when significant depression was also observed. In contrast, the thyroid-stimulating hormone (TSH) level was significantly increased by fourfold at day 3, returning to near normal values by day 9 postirradiation. Daily injections of physiological doses of T3 (0.3 microgram/100 g body weight) prevented the change in the myosin isozymes following whole-body irradiation. Daily pharmacological injections of T3 (3.0 micrograms/100 g body weight) to the irradiated rats produced a further decrease in the percent beta-myosin heavy chain (below control values) indicating tissue hyperthyroidism. Thus, this study suggests that the change in myosin isozymes following whole-body irradiation is caused by an alteration in thyroid hormone activity.

  2. Role of cyclic AMP sensor Epac1 in masseter muscle hypertrophy and myosin heavy chain transition induced by β2-adrenoceptor stimulation.

    Science.gov (United States)

    Ohnuki, Yoshiki; Umeki, Daisuke; Mototani, Yasumasa; Jin, Huiling; Cai, Wenqian; Shiozawa, Kouichi; Suita, Kenji; Saeki, Yasutake; Fujita, Takayuki; Ishikawa, Yoshihiro; Okumura, Satoshi

    2014-12-15

    The predominant isoform of β-adrenoceptor (β-AR) in skeletal muscle is β2-AR and that in the cardiac muscle is β1-AR. We have reported that Epac1 (exchange protein directly activated by cAMP 1), a new protein kinase A-independent cAMP sensor, does not affect cardiac hypertrophy in response to pressure overload or chronic isoproterenol (isoprenaline) infusion. However, the role of Epac1 in skeletal muscle hypertrophy remains poorly understood. We thus examined the effect of disruption of Epac1, the major Epac isoform in skeletal muscle, on masseter muscle hypertrophy induced by chronic β2-AR stimulation with clenbuterol (CB) in Epac1-null mice (Epac1KO). The masseter muscle weight/tibial length ratio was similar in wild-type (WT) and Epac1KO at baseline and was significantly increased in WT after CB infusion, but this increase was suppressed in Epac1KO. CB treatment significantly increased the proportion of myosin heavy chain (MHC) IIb at the expense of that of MHC IId/x in both WT and Epac1KO, indicating that Epac1 did not mediate the CB-induced MHC isoform transition towards the faster isoform. The mechanism of suppression of CB-mediated hypertrophy in Epac1KO is considered to involve decreased activation of Akt signalling. In addition, CB-induced histone deacetylase 4 (HDAC4) phosphorylation on serine 246 mediated by calmodulin kinase II (CaMKII), which plays a role in skeletal muscle hypertrophy, was suppressed in Epac1KO. Our findings suggest that Epac1 plays a role in β2-AR-mediated masseter muscle hypertrophy, probably through activation of both Akt signalling and CaMKII/HDAC4 signalling. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  3. A Roadmap for Reducing Cardiac Device Infections: a Review of Epidemiology, Pathogenesis, and Actionable Risk Factors to Guide the Development of an Infection Prevention Program for the Electrophysiology Laboratory.

    Science.gov (United States)

    Branch-Elliman, Westyn

    2017-08-16

    Cardiovascular implantable electronic device (CIED) infections are highly morbid, common, and costly, and rates are increasing (Sohail et al. Arch Intern Med 171(20):1821-8 2011; Voigt et al. J Am Coll Cardiol 48(3):590-1 2006). Factors that contribute to the development of CIED infections include patient factors (comorbid conditions, self-care, microbiome), procedural details (repeat procedure, contamination during procedure, appropriate pre-procedural prep, and antimicrobial use), environmental and organizational factors (patient safety culture, facility barriers, such as lack of space to store essential supplies, quality of environmental cleaning), and microbial factors (type of organism, virulence of organism). Each of these can be specifically targeted with infection prevention interventions. Basic prevention practices, such as administration of systemic antimicrobials prior to incision and delaying the procedure in the setting of fever or elevated INR, are helpful for day-to-day prevention of cardiac device infections. Small single-center studies provide proof-of-concept that bundled prevention interventions can reduce infections, particularly in outbreak settings. However, data regarding which prevention strategies are the most important is limited as are data regarding the optimal prevention program for day-to-day prevention (Borer et al. Infect Control Hosp Epidemiol 25(6):492-7 2004; Ahsan et al. Europace 16(10):1482-9 2014). Evolution of infection prevention programs to include ambulatory and procedural areas is crucial as healthcare delivery is increasingly provided outside of hospitals and operating rooms. The focus on traditional operating rooms and inpatient care leaves the vast majority of healthcare delivery-including cardiac device implantations in the electrophysiology laboratory-uncovered.

  4. An International External Validation Study of the 2014 European Society of Cardiology Guideline on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (Evidence from HCM)

    DEFF Research Database (Denmark)

    O'Mahony, Constantinos; Jichi, Fatima; Ommen, Steve R

    2018-01-01

    Background -Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require prophylactic implantable cardioverter defibrillator (ICD) is challenging. In 2014, the European Society of Cardiology (ESC) proposed a new risk stratification meth...

  5. Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23.

    Science.gov (United States)

    Yan, Ling; Bowman, Marion A Hofmann

    Cardiovascular disease including left ventricular hypertrophy, diastolic dysfunction and ectopic valvular calcification are common in patients with chronic kidney disease (CKD). Both S100A12 and fibroblast growth factor 23 (FGF23) have been identified as biomarkers of cardiovascular morbidity and mortality in patients with CKD. We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD. This review paper focuses on S100 proteins and their receptor for advanced glycation end products (RAGE) and summarizes recent findings obtained in novel developed transgenic hBAC-S100 mice that express S100A12 and S100A8/9 proteins. A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9 and S100A12 was expressed in C57BL/6J mice (hBAC-S100). CKD was induced by ureteral ligation, and hBAC-S100 mice and WT mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased FGF23 in the heart, left ventricular hypertrophy (LVH), diastolic dysfunction, focal cartilaginous metaplasia and calcification of the mitral and aortic valve annulus together with aortic valve sclerosis. This phenotype was not observed in WT mice with CKD or in hBAC-S100 mice lacking RAGE with CKD, suggesting that the inflammatory milieu mediated by S100/RAGE promotes pathological cardiac hypertrophy in CKD. In vitro, inflammatory stimuli including IL-6, TNFα, LPS, or serum from hBAC-S100 mice up regulated FGF23 mRNA and protein in primary murine neonatal and adult cardiac fibroblasts. Taken together, our study shows that myeloid-derived human S100/calgranulin is associated with the development of cardiac hypertrophy and ectopic cardiac calcification in a RAGE dependent manner in a mouse model of CKD. We speculate that FGF23 produced by cardiac fibroblasts in response to cytokines may act in a paracrine manner to accelerate LVH and diastolic

  6. Effect of Berberine on PPARα/NO Activation in High Glucose- and Insulin-Induced Cardiomyocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Mingfeng Wang

    2013-01-01

    Full Text Available Rhizoma coptidis, the root of Coptis chinensis Franch, has been used in China as a folk medicine in the treatment of diabetes for thousands of years. Berberine, one of the active ingredients of Rhizoma coptidis, has been reported to improve symptoms of diabetes and to treat experimental cardiac hypertrophy, respectively. The objective of this study was to evaluate the potential effect of berberine on cardiomyocyte hypertrophy in diabetes and its possible influence on peroxisome proliferator-activated receptor-α (PPARα/nitric oxide (NO signaling pathway. The cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L and insulin (0.1 μmol/L (HGI was characterized in rat primary cardiomyocyte by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expression were measured by western blot and real-time RT-PCR, respectively. The enzymatic activity of NO synthase (NOS was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. HGI significantly induced cardiomyocyte hypertrophy and decreased the expression of PPARα and endothelial NOS at the mRNA and protein levels, which occurred in parallel with declining NOS activity and NO concentration. The effect of HGI was inhibited by berberine (0.1 to 100 μmol/L, fenofibrate (0.3 μmol/L, or L-arginine (100 μmol/L. MK886 (0.3 μmol/L, a selective PPARα antagonist, could abolish the effects of berberine and fenofibrate. NG-nitro-L-arginine-methyl ester (100 μmol/L, a NOS inhibitor, could block the effects of L-arginine, but only partially blocked the effects of berberine. These results suggest that berberine can blunt HGI-induced cardiomyocyte hypertrophy in vitro, through the activation of the PPARα/NO signaling pathway.

  7. Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

    Science.gov (United States)

    Chen, Si; Knight, Walter E; Yan, Chen

    2018-04-23

    Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

  8. Regulation of cardiac microRNAs by serum response factor

    Directory of Open Access Journals (Sweden)

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  9. Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep Apnea.

    Science.gov (United States)

    Yamaguchi, Tasuku; Takata, Yoshifumi; Usui, Yasuhiro; Asanuma, Ryoko; Nishihata, Yosuke; Kato, Kota; Shiina, Kazuki; Yamashina, Akira

    2016-03-01

    Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing. In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography. LV mass index significantly correlated with IAD (r = 0.203, P intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wachtell, K.; Palmieri, V.; Olsen, M.H.

    2002-01-01

    in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow...... geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage....

  11. Primary prevention of sudden cardiac death of the young athlete: the controversy about the screening electrocardiogram and its innovative artificial intelligence solution.

    Science.gov (United States)

    Chang, Anthony C

    2012-03-01

    The preparticipation screening for athlete participation in sports typically entails a comprehensive medical and family history and a complete physical examination. A 12-lead electrocardiogram (ECG) can increase the likelihood of detecting cardiac diagnoses such as hypertrophic cardiomyopathy, but this diagnostic test as part of the screening process has engendered considerable controversy. The pro position is supported by argument that international screening protocols support its use, positive diagnosis has multiple benefits, history and physical examination are inadequate, primary prevention is essential, and the cost effectiveness is justified. Although the aforementioned myriad of justifications for routine ECG screening of young athletes can be persuasive, several valid contentions oppose supporting such a policy, namely, that the sudden death incidence is very (too) low, the ECG screening will be too costly, the false-positive rate is too high, resources will be allocated away from other diseases, and manpower is insufficient for its execution. Clinicians, including pediatric cardiologists, have an understandable proclivity for avoiding this prodigious national endeavor. The controversy, however, should not be focused on whether an inexpensive, noninvasive test such as an ECG should be mandated but should instead be directed at just how these tests for young athletes can be performed in the clinical imbroglio of these disease states (with variable genetic penetrance and phenotypic expression) with concomitant fiscal accountability and logistical expediency in this era of economic restraint. This monumental endeavor in any city or region requires two crucial elements well known to business scholars: implementation and execution. The eventual solution for the screening ECG dilemma requires a truly innovative and systematic approach that will liberate us from inadequate conventional solutions. Artificial intelligence, specifically the process termed "machine

  12. [Molecular mechanisms of skeletal muscle hypertrophy].

    Science.gov (United States)

    Astratenkova, I V; Rogozkin, V A

    2014-06-01

    Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

  13. Hypertrophied hearts: what of sevoflurane cardioprotection?

    DEFF Research Database (Denmark)

    Larsen, Jens Kjærgaard Rolighed; Smerup, Morten Holdgaard; Hasenkam, John Michael

    2009-01-01

    pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted......-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated...

  14. Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle Tracking Echocardiography.

    Science.gov (United States)

    Iio, Chiharuko; Inoue, Katsuji; Nishimura, Kazuhisa; Fujii, Akira; Nagai, Takayuki; Suzuki, Jun; Okura, Takafumi; Higaki, Jitsuo; Ogimoto, Akiyoshi

    2015-12-01

    The pathological process of left ventricular (LV) hypertrophy is associated with left atrial (LA) remodeling. This study was aimed to evaluate the prognostic value of LA strain parameters in patients with pathological LV hypertrophy. This study included 95 patients with hypertensive heart disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac amyloidosis (CA: n = 15), and control subjects (n = 20). We used two-dimensional speckle tracking echocardiography (STE) to analyze LA global strain. LA electromechanical conduction time (EMT) at the septal (EMT-septal) and lateral wall (EMT-lateral), and their time difference (EMT-diff) were calculated. The incidence of cardiac death and heart failure hospitalization was defined as major cardiac events and that of atrial fibrillation as secondary outcome. Left atrial volume index was increased and LA booster strain was decreased in the HCM and CA groups compared with the HHD group. EMT-lateral was increased in the diseased groups compared with the control. EMT-diff was prolonged in the CA group compared with the HCM group. During the follow-up period (mean 3.4 years), major cardiac events and atrial fibrillation occurred in 17 and 13 patients, respectively. The occurrence of atrial fibrillation was associated with CA etiology, E/e', LA volume index, LAa, and EMT-lateral. The incidence of major cardiac events was independently correlated with LA volume index and EMT-diff in multivariate analysis. This study suggested that the EMT-diff could discriminate patients with a high risk of cardiac events among patients with pathological LV hypertrophy. © 2015, Wiley Periodicals, Inc.

  15. The left atrium, atrial fibrillation, and the risk of stroke in hypertensive patients with left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Wachtell, K.; Devereux, R.B.; Lyle, P.A.

    2008-01-01

    was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV......The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment...... hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease Udgivelsesdato: 2008/12...

  16. Diagnostic electrocardiographic dyad criteria of emphysema in left ventricular hypertrophy.

    Science.gov (United States)

    Lanjewar, Swapnil S; Chhabra, Lovely; Chaubey, Vinod K; Joshi, Saurabh; Kulkarni, Ganesh; Kothagundla, Chandrasekhar; Kaul, Sudesh; Spodick, David H

    2013-01-01

    The electrocardiographic diagnostic dyad of emphysema, namely a combination of the frontal vertical P-vector and a narrow QRS duration, can serve as a quasidiagnostic marker for emphysema, with specificity close to 100%. We postulated that the presence of left ventricular hypertrophy in emphysema may affect the sensitivity of this electrocardiographic criterion given that left ventricular hypertrophy generates prominent left ventricular forces and may increase the QRS duration. We reviewed the electrocardiograms and echocardiograms for 73 patients with emphysema. The patients were divided into two groups based on the presence or absence of echocardiographic evidence of left ventricular hypertrophy. The P-vector, QRS duration, and forced expiratory volume in one second (FEV1) were computed and compared between the two subgroups. There was no statistically significant difference in qualitative lung function (FEV1) between the subgroups. There was no statistically significant difference in mean P-vector between the subgroups. The mean QRS duration was significantly longer in patients with left ventricular hypertrophy as compared with those without left ventricular hypertrophy. The presence of left ventricular hypertrophy may not affect the sensitivity of the P-vector verticalization when used as a lone criterion for diagnosing emphysema. However, the presence of left ventricular hypertrophy may significantly reduce the sensitivity of the electrocardiographic diagnostic dyad in emphysema, as it causes a widening of the QRS duration.

  17. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-01-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

  18. The preventive effect of statin therapy on new-onset and recurrent atrial fibrillation in patients not undergoing invasive cardiac interventions ☆

    DEFF Research Database (Denmark)

    Bang, Casper Niels Furbo; Greve, Anders M; Abdulla, Jawdat

    2013-01-01

    BACKGROUND: Previous meta-analyses suggest that pre-procedural use of statin therapy may reduce atrial fibrillation (AF) following invasive cardiac interventions (coronary artery by-pass grafting and percutaneous coronary intervention). However, the current evidence on the benefit of statins...... unrelated to invasive cardiac interventions has not been clarified systematically. METHODS: Through a systematic literature search, trials examining the effect of statin therapy on AF were selected. Trials using statins before any percutaneous or surgical cardiac interventions were excluded. RESULTS......: The search identified 11 randomized and 16 observational eligible studies, totaling 106,640 patients receiving statin therapy and 129,305 serving as controls. Fourteen studies investigated the effect of statins on new-onset AF, 13 studies investigated the effect of statins on recurrent AF and one in both new...

  19. Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

    Science.gov (United States)

    Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J

    2015-04-01

    Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Painful unilateral temporalis muscle enlargement: reactive masticatory muscle hypertrophy.

    Science.gov (United States)

    Katsetos, Christos D; Bianchi, Michael A; Jaffery, Fizza; Koutzaki, Sirma; Zarella, Mark; Slater, Robert

    2014-06-01

    An instance of isolated unilateral temporalis muscle hypertrophy (reactive masticatory muscle hypertrophy with fiber type 1 predominance) confirmed by muscle biopsy with histochemical fiber typing and image analysis in a 62 year-old man is reported. The patient presented with bruxism and a painful swelling of the temple. Absence of asymmetry or other abnormalities of the craniofacial skeleton was confirmed by magnetic resonance imaging and cephalometric analyses. The patient achieved symptomatic improvement only after undergoing botulinum toxin injections. Muscle biopsy is key in the diagnosis of reactive masticatory muscle hypertrophy and its distinction from masticatory muscle myopathy (hypertrophic branchial myopathy) and other non-reactive causes of painful asymmetric temporalis muscle enlargement.

  1. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

    Directory of Open Access Journals (Sweden)

    Chia-Ter Chao

    2015-01-01

    Full Text Available Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.

  2. Cardiac arrest

    Science.gov (United States)

    ... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

  3. Cardiac Ochronosis

    Science.gov (United States)

    Erek, Ersin; Casselman, Filip P.A.; Vanermen, Hugo

    2004-01-01

    We report the case of 67-year-old woman who underwent aortic valve replacement and mitral valve repair due to ochronotic valvular disease (alkaptonuria), which was diagnosed incidentally during cardiac surgery. PMID:15745303

  4. Cardiac catheterization

    Science.gov (United States)

    ... tests. However, it is very safe when done by an experienced team. The risks include: Cardiac tamponade Heart attack Injury to a coronary artery Irregular heartbeat Low blood pressure Reaction to the contrast dye Stroke Possible complications ...

  5. Postural Tachycardia Syndrome and Vasovagal Syncope: A Hidden Case of Obstructive Cardiomyopathy without Severe Septal Hypertrophy.

    Science.gov (United States)

    Mayuga, Kenneth A; Ho, Natalie; Shields, Robert W; Cremer, Paul; Rodriguez, L Leonardo

    2018-01-01

    A 36-year-old female with symptoms of orthostatic intolerance and syncope was diagnosed with vasovagal syncope on a tilt table test and with postural tachycardia syndrome (POTS) after a repeat tilt table test. However, an echocardiogram at our institution revealed obstructive cardiomyopathy without severe septal hypertrophy, with a striking increase in left ventricular outflow tract gradient from 7 mmHg at rest to 75 mmHg during Valsalva, with a septal thickness of only 1.3 cm. Cardiac MRI showed an apically displaced multiheaded posteromedial papillary muscle with suggestion of aberrant chordal attachments to the anterior mitral leaflet contributing to systolic anterior motion of the mitral valve. She underwent surgery with reorientation of the posterior medial papillary muscle head, resection of the tethering secondary chordae to the A1 segment of the mitral valve, chordal shortening and tacking of the chordae to the A1 and A2 segments of the mitral valve, and gentle septal myectomy. After surgery, she had significant improvement in her prior symptoms. To our knowledge, this is the first reported case of obstructive cardiomyopathy without severe septal hypertrophy with abnormalities in papillary muscle and chordal attachment, in a patient diagnosed with vasovagal syncope and POTS.

  6. Postural Tachycardia Syndrome and Vasovagal Syncope: A Hidden Case of Obstructive Cardiomyopathy without Severe Septal Hypertrophy

    Directory of Open Access Journals (Sweden)

    Kenneth A. Mayuga

    2018-01-01

    Full Text Available A 36-year-old female with symptoms of orthostatic intolerance and syncope was diagnosed with vasovagal syncope on a tilt table test and with postural tachycardia syndrome (POTS after a repeat tilt table test. However, an echocardiogram at our institution revealed obstructive cardiomyopathy without severe septal hypertrophy, with a striking increase in left ventricular outflow tract gradient from 7 mmHg at rest to 75 mmHg during Valsalva, with a septal thickness of only 1.3 cm. Cardiac MRI showed an apically displaced multiheaded posteromedial papillary muscle with suggestion of aberrant chordal attachments to the anterior mitral leaflet contributing to systolic anterior motion of the mitral valve. She underwent surgery with reorientation of the posterior medial papillary muscle head, resection of the tethering secondary chordae to the A1 segment of the mitral valve, chordal shortening and tacking of the chordae to the A1 and A2 segments of the mitral valve, and gentle septal myectomy. After surgery, she had significant improvement in her prior symptoms. To our knowledge, this is the first reported case of obstructive cardiomyopathy without severe septal hypertrophy with abnormalities in papillary muscle and chordal attachment, in a patient diagnosed with vasovagal syncope and POTS.

  7. Nuclear cardiac

    International Nuclear Information System (INIS)

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

  8. Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

    Science.gov (United States)

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-12-02

    Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  9. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  10. Ictal Cardiac Ryhthym Abnormalities.

    Science.gov (United States)

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy.

  11. Arrhythmia as a cardiac manifestation in MELAS syndrome.

    Science.gov (United States)

    Thomas, Tamara; Craigen, William J; Moore, Ryan; Czosek, Richard; Jefferies, John L

    2015-09-01

    A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) syndrome had progressive left ventricular hypertrophy (LVH) on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.

  12. High-Target vs Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients - A Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S

    2018-01-01

    .71). No significant difference was observed in frequency of severe adverse events. Conclusions -Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower MAP during cardiopulmonary bypass did not seem to affect the volume or numbers of new cerebral infarcts. Clinical Trial Registration -URL...

  13. Sudden cardiac arrest in sports - need for uniform registration: A Position Paper from the Sport Cardiology Section of the European Association for Cardiovascular Prevention and Rehabilitation.

    Science.gov (United States)

    Solberg, E E; Borjesson, M; Sharma, S; Papadakis, M; Wilhelm, M; Drezner, J A; Harmon, K G; Alonso, J M; Heidbuchel, H; Dugmore, D; Panhuyzen-Goedkoop, N M; Mellwig, K-P; Carre, F; Rasmusen, H; Niebauer, J; Behr, E R; Thiene, G; Sheppard, M N; Basso, C; Corrado, D

    2016-04-01

    There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal. © The European Society of Cardiology 2015.

  14. Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Nielsen, F S

    2005-01-01

    BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2...... diabetic patients not taking antihypertensive treatment. DESIGN: Cross-sectional study. METHODS: From 1994 to 1998, M-mode echocardiography was performed by one experienced examiner in 262 consecutive, normoalbuminuric Caucasian type 2 diabetic patients, all with blood pressure ... of diabetes and blood pressure were not. Similar results were obtained for left ventricular mass index. DISCUSSION: LVH was frequent in our normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. Several potentially modifiable risk factors, such as raised BMI, poor glycaemic control...

  15. The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

    Science.gov (United States)

    Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

    To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

    Science.gov (United States)

    Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

    2017-05-01

    Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.