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  1. Mechanisms of cardiac hypertrophy in canine volume overload

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    Matsuo, T.; Carabello, B. A.; Nagatomo, Y.; Koide, M.; Hamawaki, M.; Zile, M. R.; McDermott, P. J.

    1998-01-01

    This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with [3H]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.

  2. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

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    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  3. Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

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    Jiwon Kim

    Full Text Available Non-ischemic fibrosis (NIF on cardiac magnetic resonance (CMR has been linked to poor prognosis, but its association with adverse right ventricular (RV remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.The population comprised patients with RV dysfunction (EF 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001.Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

  4. Aortocaval Fistula in Rat: A Unique Model of Volume-Overload Congestive Heart Failure and Cardiac Hypertrophy

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    Zaid Abassi

    2011-01-01

    Full Text Available Despite continuous progress in our understanding of the pathogenesis of congestive heart failure (CHF and its management, mortality remains high. Therefore, development of reliable experimental models of CHF and cardiac hypertrophy is essential to better understand disease progression and allow new therapy developement. The aortocaval fistula (ACF model, first described in dogs almost a century ago, has been adopted in rodents by several groups including ours. Although considered to be a model of high-output heart failure, its long-term renal and cardiac manifestations are similar to those seen in patients with low-output CHF. These include Na+-retention, cardiac hypertrophy and increased activity of both vasoconstrictor/antinatriureticneurohormonal systems and compensatory vasodilating/natriuretic systems. Previous data from our group and others suggest that progression of cardiorenal pathophysiology in this model is largely determined by balance between opposing hormonal forces, as reflected in states of CHF decompensation that are characterized by overactivation of vasoconstrictive/Na+-retaining systems. Thus, ACF serves as a simple, cheap, and reproducible platform to investigate the pathogenesis of CHF and to examine efficacy of new therapeutic approaches. Hereby, we will focus on the neurohormonal, renal, and cardiac manifestations of the ACF model in rats, with special emphasis on our own experience.

  5. Aortocaval Fistula in Rat: A Unique Model of Volume-Overload Congestive Heart Failure and Cardiac Hypertrophy

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    Abassi, Zaid; Goltsman, Ilia; Karram, Tony; Winaver, Joseph; Hoffman, Aaron

    2011-01-01

    Despite continuous progress in our understanding of the pathogenesis of congestive heart failure (CHF) and its management, mortality remains high. Therefore, development of reliable experimental models of CHF and cardiac hypertrophy is essential to better understand disease progression and allow new therapy developement. The aortocaval fistula (ACF) model, first described in dogs almost a century ago, has been adopted in rodents by several groups including ours. Although considered to be a mo...

  6. CHIP protects against cardiac pressure overload through regulation of AMPK

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    Schisler, Jonathan C.; Rubel, Carrie E.; Zhang, Chunlian; Lockyer, Pamela; Cyr, Douglas M.; Patterson, Cam

    2013-01-01

    Protein quality control and metabolic homeostasis are integral to maintaining cardiac function during stress; however, little is known about if or how these systems interact. Here we demonstrate that C terminus of HSC70-interacting protein (CHIP), a regulator of protein quality control, influences the metabolic response to pressure overload by direct regulation of the catalytic α subunit of AMPK. Induction of cardiac pressure overload in Chip–/– mice resulted in robust hypertrophy and decreased cardiac function and energy generation stemming from a failure to activate AMPK. Mechanistically, CHIP promoted LKB1-mediated phosphorylation of AMPK, increased the specific activity of AMPK, and was necessary and sufficient for stress-dependent activation of AMPK. CHIP-dependent effects on AMPK activity were accompanied by conformational changes specific to the α subunit, both in vitro and in vivo, identifying AMPK as the first physiological substrate for CHIP chaperone activity and establishing a link between cardiac proteolytic and metabolic pathways. PMID:23863712

  7. VOLUME OVERLOAD IS ASSOCIATED WITH MALNUTRITION IN PERITONEAL DIALYSIS

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    Jin Joo Cha

    2012-06-01

    Volume overload is associated with malnutrition and seems to be an independent predictor of mortality in PD population. Further study should evaluate the effects of intervention of volume control in PD patients.

  8. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

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    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

    1997-01-01

    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  9. Featured Article: Cardioprotective effects of lysyl oxidase inhibition against volume overload-induced extracellular matrix remodeling

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    El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K

    2015-01-01

    A hallmark of heart failure (HF) is adverse extracellular matrix (ECM) remodeling, which is regulated by the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we evaluate the efficacy of LOX inhibition to prevent adverse left ventricular (LV) remodeling and dysfunction using an experimental model of HF. Sprague–Dawley rats were subjected to surgically induced volume overload (VO) by creation of aortocaval fistula (ACF). A LOX inhibitor, beta-aminopropionitrile (BAPN; 100 mg/kg/day), was administered to rats with ACF or sham surgery at eight weeks postsurgery. Echocardiography was used to assess progressive alterations in cardiac ventricular structure and function. Left ventricular (LV) catheterization was used to assess alterations in contractility, stiffness, LV pressure and volume, and other indices of cardiac function. The LV ECM alterations were assessed by: (a) histological staining of collagen, (b) protein expression of collagen types I and III, (c) hydroxyproline assay, and (d) cross-linking assay. LOX inhibition attenuated VO-induced increases in cardiac stress, and attenuated increases in interstitial myocardial collagen, total collagen, and protein levels of collagens I and III. Both echocardiography and catheterization measurements indicated improved cardiac function post-VO in BAPN treated rats vs. untreated. Inhibition of LOX attenuated VO-induced decreases in LV stiffness and cardiac function. Overall, our data indicate that LOX inhibition was cardioprotective in the volume overloaded heart. PMID:26582054

  10. Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy.

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    Yang, Liu; Wu, Qing-Qing; Liu, Yuan; Hu, Zhe-Fu; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-01-01

    Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti-bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre-treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal-regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway.

  11. Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy.

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    Xiao, Yang; Yang, Zheng; Wu, Qing-Qing; Jiang, Xiao-Han; Yuan, Yuan; Chang, Wei; Bian, Zhou Yan; Zhu, Jin Xiu; Tang, Qi-Zhu

    2017-11-01

    Lack of effective anti-cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti-hypertrophy and anti-fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti-hypertrophy and -fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross-sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B-mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3-MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B-mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899-3910, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Sex differences in volume overload in skinned fibers.

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    Bening, C; Hamouda, K; Leyh, R

    2016-10-14

    The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5-4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium

  13. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

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    Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

    2016-12-01

    Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights

  14. Volume overload and its risk factors in South African chronic kidney disease patients: an appraisal of bioimpedance spectroscopy and inferior vena cava measurements.

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    Hassan, Muzamil Olamide; Duarte, Raquel; Dix-Peek, Therese; Vachiat, Ahmed; Dickens, Caroline; Grinter, Sacha; Naidoo, Sagren; Manga, Pravin; Naicker, Saraladevi

    2016-07-01

    Fluid retention occurs early in chronic kidney disease (CKD) resulting in increased cardiovascular morbidity and mortality. This study aimed to assess volume and nutritional status among South African CKD participants and determine the relationship between malnutrition, inflammation, atherosclerosis, and volume overload using a body composition monitor (BCM). We also evaluated the usefulness of BCM measurement in assessing volume overload. 160 participants comprising hemodialysis, peritoneal dialysis, stage 3 CKD patients, and healthy controls (40 in each group) were studied. A BCM was used to assess fluid and nutritional status. Cardiac dimension measurements, and inferior vena cava diameter (IVCD) and carotid intima media thickness were assessed by echocardiography and ultrasonography, respectively. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured as markers of inflammation. Fluid overload and malnutrition were present in 68% and 63% of studied patients, respectively. Using physical examination findings as the reference measurements for volume overload, the area under the concentration curves for BCM and IVCD measurements were 0.866 (sensitivity 82%, specificity 74%, p < 0.001) and 0.727 (sensitivity 57%, specificity 70%, p < 0.001), respectively. Lean tissue index, inflammation, and atherosclerosis were associated with volume overload. Volume overload and malnutrition were common across the spectrum of South African CKD cohorts; volume overload was associated with malnutrition, inflammation, and atherosclerosis. Bioimpedance spectroscopy (BIS) is a useful and sensitive tool for the assessment of fluid status in clinically euvolumic nondialytic CKD patients.

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

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

    2015-12-01

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

  16. Augmented cardiac hypertrophy in response to pressure overload in mice lacking ELTD1.

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    Jinfeng Xiao

    Full Text Available BACKGROUND: Epidermal growth factor (EGF, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1 is developmentally upregulated in the heart. Little is known about the relationship between ELTD1 and cardiac diseases. Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT mice and ELTD1-knockout (KO mice were subjected to left ventricular pressure overload by descending aortic banding (AB. KO mice exhibited more unfavorable cardiac remodeling than WT mice 28 days post AB; this remodeling was characterized by aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls, dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac function. Analysis of signaling pathways revealed enhanced extracellular signal-regulated kinase (ERK and the c-Jun amino-terminal kinase (JNK phosphorylation in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac hypertrophy and cardiac function induced by AB-induced pressure overload by promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are suggested to originate from the activation of the ERK and JNK pathways, suggesting that ELTD1 is a potential target for therapies that prevent the development of cardiac disease.

  17. Novel mechanisms for caspase inhibition protecting cardiac function with chronic pressure overload

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    Park, Misun; Vatner, Stephen F.; Yan, Lin; Gao, Shumin; Yoon, Seunghun; Lee, Grace Jung Ah; Xie, Lai-Hua; Kitsis, Richard N.; Vatner, Dorothy E.

    2013-01-01

    Myocyte apoptosis is considered a major mechanism in the pathogenesis of heart failure. Accordingly, manipulations that inhibit apoptosis are assumed to preserve cardiac function by maintaining myocyte numbers. We tested this assumption by examining the effects of caspase inhibition (CI) on cardiac structure and function in C57BL/6 mouse with pressure overload model induced by transverse aortic constriction (TAC). CI preserved left ventricular (LV) function following TAC compared with the veh...

  18. Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

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    Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

    2016-08-15

    Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Pioglitazone Alleviates Cardiac Fibrosis and Inhibits Endothelial to Mesenchymal Transition Induced by Pressure Overload

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    Wen-Ying Wei

    2017-12-01

    Full Text Available Background/Aims: Cardiac fibrosis, characterized by an unbalanced production and degradation of extracellular matrix components, is a common pathophysiology of multiple cardiovascular diseases. Recent studies suggested that endothelial to mesenchymal transition (EndMT could be a source of activated fibroblasts and contribute to cardiac fibrosis. Here, the role of pioglitazone (PIO in cardiac fibrosis and EndMT was elaborated. Methods: Male C57BL/6 mice were subjected to aortic banding (AB, which was used to construct a model of pressure overload-induced cardiac hypertrophy. PIO and GW9662 was given for 4 weeks to detect the effects of PIO on EndMT. Results: Our results showed PIO treatment attenuated cardiac hypertrophy, dysfunction and fibrosis response to pressure overload. Mechanistically, PIO suppressed the TGF-β/Smad signaling pathway activated by 4-week AB surgery. Moreover, PIO dramatically inhibited EndMT in vivo and in vitro stimulated by pressure overload or TGF-β. A selective antagonist of PPAR-γ, GW9662, neutralized the anti-fibrotic effect and abolished the inhibitory effect of EndMT during the treatment of PIO. Conclusion: Our data implied that PIO exerts an alleviative effect on cardiac fibrosis via inhibition of the TGF-β/Smad signaling pathway and EndMT by activating PPAR-γ.

  20. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

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    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  1. Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

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    Porter John B

    2010-04-01

    Full Text Available Abstract Aim We aimed to define reference ranges for right ventricular (RV volumes, ejection fraction (EF in thalassemia major patients (TM without myocardial iron overload. Methods and results RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance. All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017, which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%. RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027, with a higher upper limit (132 vs 110 mL/m2 but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2. The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p Conclusion The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.

  2. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

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    Mariane de Montalembert

    Full Text Available The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS. In patients with sickle cell anemia (SCA, iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15% patients with thalassemia, none with SCA, and 4 (16% with MDS. The liver iron content (LIC ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29. Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001. Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001. Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  3. Estrogenic modulation of inflammation-related genes in male rats following volume overload

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    McLarty, Jennifer L.; Meléndez, Giselle C.; Levick, Scott P.; Bennett, Shanté; Sabo-Attwood, Tara; Brower, Gregory L.

    2012-01-01

    Our laboratory has previously reported significant increases of the proinflammatory cytokine TNF-α in male hearts secondary to sustained volume overload. These elevated levels of TNF-α are accompanied by left ventricular (LV) dilatation and cardiac dysfunction. In contrast, estrogen has been shown to protect against this adverse cardiac remodeling in both female and male rats. The purpose of this study was to determine whether estrogen has an effect on inflammation-related genes that contribute to this estrogen-mediated cardioprotection. Myocardial volume overload was induced by aortocaval fistula in 8 wk old male Sprague-Dawley rats (n = 30), and genes of interest were identified using an inflammatory PCR array in Sham, Fistula, and Fistula + Estrogen-treated (0.02 mg/kg per day beginning 2 wk prior to fistula) groups. A total of 55 inflammatory genes were modified (≥2-fold change) at 3 days postfistula. The number of inflammatory gene was reduced to 21 genes by estrogen treatment, whereas 13 genes were comparably modulated in both fistula groups. The most notable were TNF-α, which was downregulated by estrogen, and the TNF-α receptors, which were differentially regulated by estrogen. Specific genes related to arachidonic acid metabolism were downregulated by estrogen, including cyclooxygenase-1 and -2. Finally, gene expression for the β1-integrin cell adhesion subunit was significantly upregulated in the LV of estrogen-treated animals. Protein levels reflected the changes observed at the gene level. These data suggest that estrogen provides its cardioprotective effects, at least in part, via genomic modulation of numerous inflammation-related genes. PMID:22274565

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

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    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.

  5. Non-invasive diagnosis and follow-up of right ventricular overload

    NARCIS (Netherlands)

    Henkens, Ivo Reinier

    2008-01-01

    Right ventricular overload covers a spectrum ranging from volume overload to pressure overload, and often is a combination of these, compromising cardiac function. Part I focuses on right ventricular volume overload in adults with Fallot’s tetralogy corrected in early childhood. We determined

  6. [Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload].

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    Zhao, Mingyue; Qin, Yupei; Lu, Lihui; Tang, Xiaoju; Wu, Wenchao; Fu, Hua; Liu, Xiaojing

    2015-06-01

    The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload. SD rats underwent transverse abdominal aortic constriction (TAC) operation for establishing cardiac hypertrophy model. The structure and function of the left ventricle of rats were evaluated via echocardiography, left ventricular mass index, the expression of markers of cardiac hypertrophy and histological detection. Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3, the necroptosis markers) respectively. Four weeks after TAC operation, rat model for cardiac hypertrophy was established. The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3 in the rat heart hypertrophic tissues after TAC for 4 weeks were increased significantly compared with those in the sham group. HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models. By transmission electron microscope, we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models. Treatment with losartan used, the selective antagonist of angiotensin II type I receptor could improve the cardiac function of TAC rats. Moreover, losartan treatment decreased the expression of RIPK1 and RIPK3 in heart tissues of TAC rats. The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload, and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

  7. Sarcomeric lesions and remodeling proximal to intercalated disks in overload-induced cardiac hypertrophy.

    Science.gov (United States)

    Kebir, Sied; Orfanos, Zacharias; Schuld, Julia; Linhart, Markus; Lamberz, Christian; van der Ven, Peter F M; Schrickel, Jan; Kirfel, Gregor; Fürst, Dieter O; Meyer, Rainer

    2016-10-15

    Pressure overload induces cardiac remodeling involving both the contractile machinery and intercalated disks (IDs). Filamin C (FlnC) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adapters localizing in IDs of higher vertebrates. Knockout of the gene encoding Xin (Xirp1) in mice leads to a mild cardiac phenotype with ID mislocalization. In order to amplify this phenotype, we performed transverse aortic constriction (TAC) on control and Xirp1-deficient mice. TAC induced similar left ventricular hypertrophy in both genotypes, suggesting that the lack of Xin does not lead to higher susceptibility to cardiac overload. However, in both genotypes, FlnC appeared in "streaming" localizations across multiple sarcomeres proximal to the IDs, suggesting a remodeling response. Furthermore, FlnC-positive areas of remodeling, reminiscent of sarcomeric lesions previously described for skeletal muscles (but so far unreported in the heart), were also observed. These adaptations reflect a similarly strong effect of the pressure induced by TAC in both genotypes. However, 2 weeks post-operation TAC-treated knockout hearts had reduced levels of connexin43 and slightly increased incidents of ventricular tachycardia compared to their wild-type (WT) counterparts. Our findings highlight the FlnC-positive sarcomeric lesions and ID-proximal streaming as general remodeling responses in cardiac overload-induced hypertrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.

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    Bindiya Patel

    Full Text Available Although cardiac and splenic mononuclear phagocytes (MPs, i.e., monocytes, macrophages and dendritic cells (DCs, are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF, and that MP depletion would ameliorate remodeling.C57BL/6 mice were subjected to transverse aortic constriction (TAC or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206- cardiac macrophages early (1 w after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w, during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice.Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Correlation between volume overload, chronic inflammation, and left ventricular dysfunction in chronic kidney disease patients.

    Science.gov (United States)

    Hassan, Muzamil Olamide; Duarte, Raquel; Dix-Peek, Therese; Vachiat, Ahmed; Naidoo, Sagren; Dickens, Caroline; Grinter, Sacha; Manga, Pravin; Naicker, Saraladevi

    Fluid overload is common in chronic kidney disease (CKD) patients, potentially driving chronic inflammation and left ventricular dysfunction. We investigated the association between volume overload, chronic inflammation, and left ventricular dysfunction across subgroups of CKD patients. The study included 160 participants, comprising peritoneal dialysis (PD), hemodialysis (HD), stage-3 CKD patients, and age- and sex-matched controls (40 in each group). Fluid status was assessed using a body composition monitor (BCM); serum endotoxin, lipopolysaccharide binding protein (LBP), C-reactive protein (CRP). and interleukin-6 (IL-6) levels were measured as markers of inflammation. Echocardiography was done to assess left ventricular dimension and function. Endotoxemia and volume overload were common across the spectrum of CKD patients and were aggravated by worsening kidney function. Among HD cohorts, postdialysis endotoxemia was increased among patients with dialysis-induced hemodynamic instability and was also closely related to ultrafiltration volume. Endotoxin, IL-6, CRP, and LBP levels were elevated in patients with volume overload compared to euvolemic patients (p < 0.05). Patients with elevated circulating endotoxemia had higher left ventricular mass index (LVMI) compared to patients with lower endotoxin levels. Fluid overload correlated with endotoxin levels, IL-6, and LVMI; while LVMI correlated weakly with LBP and CRP. CKD patients typically presented with significant endotoxemia and overt volume overload, which may contribute significantly to chronic low-grade inflammation and left ventricular dysfunction. An additive contribution from hemodialysis treatment may strongly enhance the severity of endotoxemia in HD patients.

  11. Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload.

    Science.gov (United States)

    Li, Wei-Ming; Zhao, Yi-Fan; Zhu, Guo-Fu; Peng, Wen-Hui; Zhu, Meng-Yun; Yu, Xue-Jing; Chen, Wei; Xu, Da-Chun; Xu, Ya-Wei

    2017-01-01

    Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy. © 2016 The

  12. Volume Overload in Heart Failure: An Evidence-Based Review of Strategies for Treatment and Prevention.

    Science.gov (United States)

    Houston, Brian A; Kalathiya, Rohan J; Kim, Daniel A; Zakaria, Sammy

    2015-09-01

    Acute decompensated heart failure is the leading cause of hospital admission in the United States, with a high risk of readmission within 30 days. Most acute decompensated heart failure admissions are driven by congestive signs and symptoms resulting from fluid and sodium overload. We reviewed the evidence base addressing the management and prevention of fluid overload in heart failure, focusing on recent clinical trials. All the references in this review were obtained through PubMed and had at least 1 of the following key words: heart failure and volume overload, congestion, loop diuretics, thiazide diuretics, aldosterone antagonists, dopamine, cardiorenal syndrome, nesiritide, vasopressin antagonists, ultrafiltration, sodium restriction, fluid restriction, telemonitoring, and invasive hemodynamic monitoring. We also reviewed relevant references cited in the obtained articles, especially articles addressing methods of treating or preventing volume overload in patients with heart failure. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  13. [Functional significance of left ventricular distortion in patients with right ventricular volume or pressure overloading].

    Science.gov (United States)

    Maeda, T; Matsuzaki, M; Anno, Y; Toma, Y; Maeda, R; Konishi, M; Okada, K; Tanaka, N; Suetsugu, M; Ono, S

    1986-06-01

    To evaluate the effects of left ventricular (LV) distortion on its pump function, the LV cavity shape was analyzed by two-dimensional echocardiography in normal subjects and in patients with right ventricular (RV) volume or pressure overload. The functional significance of LV distortion in the short-axis sections was evaluated by an index of the efficiency of ejection (E) of endocardial circumferential fiber length (ECL) shortening in reducing LV cavity area during systole; E = measured systolic area reduction/ideal systolic area reduction X 100 (%), where an ideal area at end-diastole or end-systole was computed for the measured ECL, assuming its shape to be perfectly circular (ideal area = ECL2/4 pi), and then an ideal systolic area reduction was determined. E at the chordal level was termed Ech. In patients with atrial septal defect (ASD), the LV cavity was distorted at end-diastole and became more circular at end-systole. Since this characteristic change during systole diminished the E, and the values of E at the chordal level (Ech) were significantly lower in ASD than those in normal subjects (89.4 +/- 4.4% vs 98.3 +/- 0.8%, p less than 0.001), strongly suggesting impairment of the efficiency of LV pump function in ASD. In patients with pulmonary hypertension, the LV cavity was more distorted at systole, and a decrease in cavity area at end-systole with the distorted LV contributed to increased systolic area reduction. Thus, the values of Ech in this group exceeded 100% in five of nine patients (103.8 +/- 12.3%). In other words, when marked RV systolic overload exists, an increase in LV systolic area reduction due to progressive LV compression will occur against LV systolic pressure. This phenomenon suggests the existence of "cardiac massage on the LV by the RV with elevated pressure". In conclusion, it was strongly suggested that the efficiency of LV pump function is modulated by RV overload through dynamic changes in the LV shape.

  14. Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy A redução da pressão de perfusão coronariana está associada com a fibrose endocárdica no modelo de hipertrofia por sobrecarga de volume em ratos

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    Maria Carolina Guido

    2004-01-01

    Full Text Available Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each and their respective controls (sham-operated controls - Sh, Sh4 and Sh8 (8 rats each. Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg, used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1 than in Sh8 (100.8 ± 1.3, but comparable between aortocaval fistula 4 (50.0 ± 8.9 and Sh4 (84.8 ± 2.3. Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P No remodelamento que se segue às sobrecargas de volume não é descrito o aumento de fibrose miocárdica. Após o infarto, entretanto, há hipertrofia do miocárdio remoto com acúmulo de fibrose, particularmente no subendoc

  15. Smad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload-Induced Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Lu, Yu-Yan; Xu, Da-Chun; Zhao, Yi-Fan; Zhu, Guo-Fu; Zhu, Meng-Yun; Liu, Wei-Jing; Yu, Xue-Jing; Chen, Wei; Liu, Zheng; Xu, Ya-Wei

    2016-10-26

    Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear. Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes. Accordingly, SNIP1 deficiency significantly exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac-specific overexpression of SNIP1 markedly recovered pressure overload-induced cardiac hypertrophy and fibrosis. Besides that, SNIP1 protected neonatal rat cardiomyocytes against angiotensin II-induced hypertrophy in vitro. Moreover, we identified that SNIP1 suppressed nuclear factor-κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor-κB signaling by a cardiac-specific conditional inhibitor of κB S 32A/S36A transgene blocked these adverse effects of SNIP1 deficiency on hearts. Together, our findings demonstrated that SNIP1 had protective effects in pressure overload-induced pathological cardiac hypertrophy via inhibition of nuclear factor-κB signaling. Thus, SNIP1 may be a novel approach for the treatment of heart failure. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

    Science.gov (United States)

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

    2016-05-04

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

  17. 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

    Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system...... 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...

  18. Normal and high eNOS levels are detrimental in both mild and severe cardiac pressure-overload.

    Science.gov (United States)

    van Deel, Elza D; Octavia, Yanti; de Boer, Martine; Juni, Rio P; Tempel, Dennie; van Haperen, Rien; de Crom, Rini; Moens, An L; Merkus, Daphne; Duncker, Dirk J

    2015-11-01

    Nitric oxide (NO) produced by endothelial NO synthase (eNOS) exerts beneficial effects in a variety of cardiovascular disease states. Studies on the benefit of eNOS activity in pressure-overload cardiac hypertrophy and dysfunction produced by aortic stenosis are equivocal, which may be due to different expression levels of eNOS or different severities of pressure-overload. Consequently, we investigated the effects of eNOS-expression level on cardiac hypertrophy and dysfunction produced by mild or severe pressure-overload. To unravel the impact of eNOS on pressure-overload cardiac dysfunction we subjected eNOS deficient, wildtype and eNOS overexpressing transgenic (eNOS-Tg) mice to 8weeks of mild or severe transverse aortic constriction (TAC) and studied cardiac geometry and function at the whole organ and tissue level. In both mild and severe TAC, lack of eNOS ameliorated, whereas eNOS overexpression aggravated, TAC-induced cardiac remodeling and dysfunction. Moreover, the detrimental effects of eNOS in severe TAC were associated with aggravation of TAC-induced NOS-dependent oxidative stress and by further elevation of eNOS monomer levels, consistent with enhanced eNOS uncoupling. In the presence of TAC, scavenging of reactive oxygen species with N-acetylcysteine reduced eNOS S-glutathionylation, eNOS monomer and NOS-dependent superoxide levels in eNOS-Tg mice to wildtype levels. Accordingly, N-acetylcysteine improved cardiac function in eNOS-Tg but not in wildtype mice with TAC. In conclusion, independent of the severity of TAC, eNOS aggravates cardiac remodeling and dysfunction, which appears due to TAC-induced eNOS uncoupling and superoxide production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Dietary omega-3 polyunsaturated fatty acids suppress NHE-1 upregulation in a rabbit model of volume- and pressure-overload

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    Marcel evan Borren

    2012-04-01

    Full Text Available Background: Increased consumption of omega-3 polyunsaturated fatty acids (3-PUFAs from fish oil may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HF. The cardiac Na+/H+-exchanger (NHE-1 is a key mediator for these detrimental cardiac conditions. Consequently, chronic NHE-1 inhibition appears to be a promising pharmacological tool for prevention and treatment. Acute application of the fish oil 3-PUFAs eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with 3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HF induced by volume- and pressure-overload.Methods: Rabbits were allocated to four groups. The first two groups consisted of healthy rabbits, which were fed either a diet containing 1.25% (w/w fish oil (3-PUFAs, or 1.25% high-oleic sunflower oil (9-MUFAs as control. The second two groups were also allocated to either a diet containing 3-PUFAs or 9-MUFAs, but underwent volume- and pressure-overload to induce HF. Ventricular myocytes were isolated by enzymatic dissociation and used for intracellular pH (pHi and patch clamp measurements. NHE-1 activity was measured in HEPES-buffered conditions as recovery rate from acidosis due to ammonium prepulses.Results: In healthy rabbits, NHE-1 activity in 9-MUFAs and 3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in 9-MUFAs myocytes, but not in 3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of 3-PUFA fed HF rabbits. The susceptibility to induced delayed afterdepolarizations (DADs, a cellular mechanism of arrhythmias, was lower in myocytes of HF animals fed 3- PUFAs compared to myocytes of HF animals fed9-MUFAs. In our rabbit HF model, the degree of hypertrophy was similar in the 3-PUFAs group

  20. Comparative studies on right ventricular pressure and volume overloading by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Owada, K.; Tsukahara, Y.; Kijima, M.; Miyazaki, Y.; Ono, K. (Fukushima Medical Coll. (Japan))

    1982-03-01

    Thallium-201 myocardial scintigraphy was performed in 44 patients with various heart diseases including mitral stenosis, atrial septal defect, primary pulmonary hypertension, and left atrial myxoma. The morphological findings of right ventricular (RV) free wall on the scintigram and RV/IVS (interventricular septum) uptake ratio of the images obtained from the left anterior oblique projection were studied in the patients with RV pressure or volume overloading.

  1. Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available Reactive cardiac fibrosis resulting from chronic pressure overload (PO compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs play a key role in fibrosis by activating cardiac fibroblasts (CFb, and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC. Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i extracellular accumulation of both collagen and fibronectin, (ii both basal and PDGF-stimulated activation of Pyk2, (iii nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.

  2. Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

    Science.gov (United States)

    Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

    2015-01-01

    The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

  3. β3 integrin in cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available The adhesion receptor β3 integrin regulates diverse cellular functions in various tissues. As β3 integrin has been implicated in extracellular matrix (ECM remodeling, we sought to explore the role of β3 integrin in cardiac fibrosis by using wild type (WT and β3 integrin null (β3-/- mice for in vivo pressure overload (PO and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, β3-/- mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from β3-/- mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1 expression in early time points of PO. To test if the observed impairment of ECM accumulation in β3-/- mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and β3-/- mice for adhesion to ECM proteins, cell spreading, proliferation, and migration in response to platelet derived growth factor-BB (PDGF, a growth factor known to promote fibrosis stimulation. Our results showed that β3-/- cardiac fibroblasts exhibited a significant reduction in cell-matrix adhesion, cell spreading, proliferation and migration. In addition, the activation of PDGF receptor associated tyrosine kinase and non-receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in β3-/- cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F resulted in reduced accumulation of fibronectin. These results indicate that β3 integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in PO-induced cardiac fibrosis.

  4. Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy

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    Shun Wang

    2017-12-01

    Full Text Available Background/Aims: Angiotensin II (Ang II has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK, a specific kinase for the phosphorylation of myosin light chain 2 (MLC2, plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9 inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2, myosin phosphatase 2 (MYPT2, and calmodulin (CaM were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.

  5. ZNF307 (Zinc Finger Protein 307) Acts as a Negative Regulator of Pressure Overload-Induced Cardiac Hypertrophy.

    Science.gov (United States)

    Yu, Chang-Jiang; Liang, Chen; Li, Yu-Xia; Hu, Qing-Qing; Zheng, Wei-Wan; Niu, Na; Yang, Xu; Wang, Zi-Rui; Yu, Xiao-Di; Zhang, Bao-Long; Song, Bin-Lin; Zhang, Zhi-Ren

    2017-04-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. We found that the protein expression levels of the ZNF307 (zinc finger protein 307) were significantly increased in heart samples from both human patients with dilated cardiomyopathy and mice subjected to aortic banding. Therefore, we aimed to elucidate the role of ZNF307 in the development of cardiac hypertrophy and to explore the signal transduction events that mediate the effect of ZNF307 on cardiac hypertrophy, using cardiac-specific ZNF307 transgenic (ZNF307-TG) mice and ZNF307 global knockout (ZNF307-KO) mice. The results showed that the deletion of ZNF307 potentiated aortic banding-induced pathological cardiac hypertrophy, fibrosis, and cardiac dysfunction; however, the aortic banding-induced cardiac hypertrophic phenotype was dramatically diminished by ZNF307 overexpression in mouse heart. Mechanistically, the antihypertrophic effects mediated by ZNF307 in response to pathological stimuli were associated with the direct inactivation of NF-κB (nuclear factor-κB) signaling and blockade of the nuclear translocation of NF-κB subunit p65. Furthermore, the overexpression of a degradation-resistant mutant of IκBα (IκBα S32A/S36A ) reversed the exacerbation of cardiac hypertrophy, fibrosis, and dysfunction shown in aortic banding-treated ZNF307-KO mice. In conclusion, our findings demonstrate that ZNF307 ameliorates pressure overload-induced cardiac hypertrophy by inhibiting the activity of NF-κB-signaling pathway. © 2017 American Heart Association, Inc.

  6. Cardiac FKBP12.6 overexpression protects against triggered ventricular tachycardia in pressure overloaded mouse hearts.

    Science.gov (United States)

    Vinet, Laurent; Pezet, Mylène; Bito, Virginie; Briec, François; Biesmans, Liesbeth; Rouet-Benzineb, Patricia; Gellen, Barnabas; Prévilon, Miresta; Chimenti, Stefano; Vilaine, Jean-Paul; Charpentier, Flavien; Sipido, Karin R; Mercadier, Jean-Jacques

    2012-03-01

    Alterations in RyR2 function have been proposed as a major pathophysiological mechanism of arrhythmias and heart failure (HF). Cardiac FKBP12.6 overexpression protects against myocardial infarction-induced HF and catecholamine-promoted ventricular arrhythmias. We tested the hypothesis that FKBP12.6 overexpression protects against maladaptive LVH and triggered ventricular arrhythmias following transverse aorta constriction (TAC) in the mouse. The TAC-associated mortality rate was significantly lower in male transgenic (DT) than in Ctr mice (p < 0.05). TAC-associated maladaptive hypertrophy was blunted in DT mice especially 1 month post-TAC and their SERCA2a/PLB ratio remained unchanged 1 and 2 months post-TAC. Two months after TAC, trains of 30 stimuli (burst pacing) performed following isoproterenol injection (0.2 mg/kg, ip), induced VT in 50% of the TAC-Ctr and in none of the TAC-DT mice (p = 0.022). The increase in myocyte shortening and Ca(2+) spark frequency observed in sham-operated Ctr mice in response to 50 nM isoproterenol was reduced in DT mice, and abolished in TAC-DT mice. NCX1 function was reduced in Sham-DT and TAC-DT compared with Sham-Ctr and TAC-Ctr mice, respectively (p < 0.05 for the 2 comparisons). In mice killed after isoproterenol injection and burst pacing, RyR2 S2814 phosphorylation was decreased by 50% in TAC-DT versus TAC-Ctr mice (p < 0.05), with no change in RyR2 S2808 and PLB S16 and T17 phosphorylation. Cardiac FKBP12.6 overexpression in the mouse blunts pressure overload-induced maladaptive LV remodelling and protects against catecholamine-promoted burst pacing-induced ventricular tachycardia by decreasing cardiac sensitivity to adrenergic stress and RyR2 S2814 phosphorylation, and decreasing NCX1 activity.

  7. The impact of volume overload on right heart function in end-stage renal disease patients on hemodialysis.

    Science.gov (United States)

    Ünlü, Serkan; Şahinarslan, Asife; Gökalp, Gökhan; Seçkin, Özden; Arınsoy, Selim Turgay; Boyacı, Nuri Bülent; Çengel, Atiye

    2017-12-11

    The aim of this study was to evaluate the impact of volume overload on echocardiographic parameters used for the assessment of the right ventricle (RV) and right atrium (RA), to determine volume-independent parameters and to noninvasively investigate the physio-mechanics of RV and RA by examining end-stage kidney patients before and after hemodialysis (HD). The echocardiographic images were obtained from 67 patients (49.2 ± 17.3 years, 23 f) before and after HD. Changes in echocardiographic parameters with HD were examined. The average ultrafiltrated volume was 3088.1 ± 1103.7 mL. The size of RV and RA and tricuspid annular plane systolic excursion (TAPSE) decreased after HD, whereas myocardial performance index increased. RV fractional area change and iso-volumetric contraction acceleration time remained unchanged. RV global longitudinal strain (GLS) and RV early diastolic strain rate (SR) decreased after HD. Systolic and late diastolic SR of the RV showed no statistically significant difference after HD. Longitudinal strain and SR of RA contraction were not significantly different after HD. The changes in RV GLS (r = .641, P = .027), RV free wall longitudinal strain (r = .643, P information on RA physio-mechanics. This might lead to a better evaluation of the cardiac pathophysiology and hemodynamics of patients. Moreover, providing novel volume-independent parameters for the evaluation of right heart chambers would improve the clinical perspectives of patients. © 2017, Wiley Periodicals, Inc.

  8. Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data.

    Science.gov (United States)

    Krittayaphong, Rungroj; Viprakasit, Vip; Saiviroonporn, Pairash; Siritanaratkul, Noppadol; Siripornpitak, Suvipaporn; Meekaewkunchorn, Arunotai; Kirawittaya, Thawatchai; Sripornsawan, Pornpun; Jetsrisuparb, Arunee; Srinakarin, Jiraporn; Wong, Peerapon; Phalakornkul, Nuttaporntira; Sinlapamongkolkul, Phakatip; Wood, John

    2017-07-01

    Prevalence of cardiac and liver iron overload in patients with thalassemia in real-world practice may vary among different regions especially in the era of widely-used iron chelation therapy. The aim of this study was to determine the prevalence of cardiac and liver iron overload in and the management patterns of patients with thalassemia in real-world practice in Thailand. We established a multicenter registry for patients with thalassemia who underwent magnetic resonance imaging (MRI) as part of their clinical evaluation. All enrolled patients underwent cardiac and liver MRI for assessment of iron overload. There were a total of 405 patients enrolled in this study. The mean age of patients was 18.8±12.5years and 46.7% were male. Two hundred ninety-six (73.1%) of patients received regular blood transfusion. Prevalence of cardiac iron overload (CIO) and liver iron overload (LIO) was 5.2% and 56.8%, respectively. Independent predictors for iron overload from laboratory information were serum ferritin and transaminase for both CIO and LIO. Serum ferritin can be used as a screening tool to rule-out CIO and to diagnose LIO. Iron chelation therapy was given in 74.6%; 15.3% as a combination therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    OpenAIRE

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P.; De Geest, Bart

    2017-01-01

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (h...

  10. Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.

    Science.gov (United States)

    Wu, Lianpin; Cao, Zhiyong; Ji, Ling; Mei, Liqin; Jin, Qike; Zeng, Jingjing; Lin, Jiafeng; Chu, Maoping; Li, Lei; Yang, Xiangjun

    2017-02-05

    We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR. Phosphorylated and total TAK1, Akt, and p38 MAPK levels were examined by Western blotting. The ratios of lung or heart/body weight, wall thickness/chamber diameter of left ventricular and cross area of cardiomyocyte were significantly reduced in TRADD knockout (KO) mice than those of wild-type mice after TAC. Moreover, cardiac hypertrophic and fibrotic markers were downregulated in TRADD knockout mice than those of wild-type mice following TAC. Protein expression analysis showed phosphorylated TAK1, p38 MAPK and AKT were upregulated after TAC in both wild-type and TRADD KO mice, phosphorylation of TAK1 and p38 MAPK was reduced more remarkably after TRADD deficiency, while phosphorylated AKT expression was similar between TRADD KO and wild-type mice following TAC. Our data suggest that TRADD KO blunts pressure overload-induced cardiac hypertrophy through mediating TAK1/p38 MAPK but not AKT phosphorylation in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

    Science.gov (United States)

    Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

    2017-07-01

    Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial

  12. Triple Diuretics and Aquaretic Strategy for Acute Decompensated Heart Failure due to Volume Overload

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    Rita Jermyn

    2013-01-01

    Full Text Available Diuretics, including furosemide, metolazone, and spironolactone, have historically been the mainstay of therapy for acute decompensated heart failure patients. The addition of an aquaretic-like vasopressin antagonist may enhance diuresis further. However, clinical experience with this quadruple combination is lacking in the acute setting. We present two hospitalized patients with acute decompensated heart failure due to massive fluid overload treated with a combination strategy of triple diuretics in conjunction with the aquaretic tolvaptan. The first patient lost 72.1 lbs. (32.7 kg with an average urine output of 3.5 to 7.5 L/day over eight days on combined therapy with furosemide, metolazone, spironolactone, and tolvaptan. The second patient similarly achieved a weight loss of 28.2 lbs. (12.8 kg over 4 days on the same treatment. Both patients maintained stable serum sodium, potassium, and creatinine over this period and remained out of the hospital for more than 30 days. Thus, patients hospitalized with acute decompensated heart failure due to volume overload can achieve euvolemia rapidly and without electrolytes disturbances using this regimen, while being under the close supervision of a team of cardiologists and nephrologists. Additionally, this therapy can potentially decrease the need for ultrafiltration and the length of hospital stay.

  13. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction

    OpenAIRE

    Chen, Ailan; Li, Wanglin; Chen, Xinyu; Shen, Yuechun; Dai, Wenjun; Dong, Qi; Li, Xinchun; Ou, Caiwen; Chen, Minsheng

    2016-01-01

    Background Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine ...

  14. Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress

    OpenAIRE

    Ning Zhang; Wen-Ying Wei; Zheng Yang; Yan Che; Ya-Ge Jin; Hai-Han Liao; Sha-sha Wang; Wei Deng; Qi-Zhu Tang

    2017-01-01

    Background/Aims: An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Methods: Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/S...

  15. Can aortic elastic parameters be used for the diagnosis of volume overload in patients with end stage renal disease.

    Science.gov (United States)

    Sayin, Muhammet R; Akpinar, Ibrahim; Cetiner, Mehmet A; Karabag, Turgut; Aydin, Mustafa; Hur, Ender; Dogan, Sait M

    2012-01-01

    We aimed here to investigate hydration status by echocardiography in end stage renal disease (ESRD) patients. 25 ESRD patients [15 males; mean age: 54.0±16.6 years; 13 hemodialysis; 12 peritoneal dialysis] were considered eligible for this study. We also examined 29 healthy volunteers as a control group (17 males; mean age: 46.5±12.8 years). Body composition analysis using the bioimpedance spectroscopy technique was performed for volume overload diagnosis. The ratio of extracellular water (ECW) to height was used as volume indices. The aortic elastic parameters were calculated by echocardiography. A correlation analyses was performed between the ratio of ECW to height indicating the volume overload and the aortic elastic parameters e.g. Aortic strain (AS), Aortic distensibility (AD) and Aortic stiffness index (ASI). The ratio of ECW to height that indicates volume overload in ESRD patients was considerably higher than that in the control group (10.25±1.98 L/m vs. 8.66±1.22 L/m, p=0.001). There was a negative correlation between the ratio of ECW to height and AS and AD and a positive correlation between the ratio of ECW to height and ASI. Given the importance of the diagnosis and follow up of volume overload, the results show that aortic elasticity measurements, being easy to perform and replicate, can be used for this purpose. Copyright © 2012 S. Karger AG, Basel.

  16. Superoxide scavenging and Akt inhibition in myocardium ameliorate pressure overload-induced NF-κB activation and cardiac hypertrophy.

    Science.gov (United States)

    Hingtgen, Shawn D; Li, Zhenbo; Kutschke, William; Tian, Xin; Sharma, Ram V; Davisson, Robin L

    2010-04-01

    Recent studies from our laboratory and others have shown that increases in cytoplasmic superoxide (O(2)(·-)) levels and Akt activation play a key role in agonist-stimulated NF-κB activation and cardiomyocyte hypertrophy in vitro. In this study, we tested the hypothesis that adenovirus (Ad)-mediated intramyocardial gene transfer of cytoplasmic superoxide dismutase (AdCu/ZnSOD) or a dominant-negative form of Akt (AdDNAkt) in mice would attenuate pressure overload-induced increases in activation of the redox-sensitive transcription factor NF-κB and cardiac hypertrophy. Adult C57BL/6 mice were subjected to thoracic aortic banding (TAB) or sham surgery, and intramyocardial injections of viral vectors (AdCu/ZnSOD, AdDNAkt, or control) were performed. There was robust transgene expression in the heart, which peaked 6-7 days after injection and then declined to undetectable levels by 12-14 days. In mice injected with AdBgL II, TAB caused a significant increase in O(2)(·-) generation and cardiac mass at 1 wk, and these responses were markedly attenuated by AdCu/ZnSOD. In addition, TAB induced time-dependent activation of NF-κB in the myocardium as measured longitudinally by in vivo bioluminescent imaging of NF-κB-dependent luciferase expression. This was also abolished by intracardiac AdCu/ZnSOD or AdDNAkt, but not the control vector. The inhibition of Akt and O(2)(·-)-mediated NF-κB activation in TAB hearts was associated with an attenuation of cardiac hypertrophy. Since a direct cause-and-effect relationship between NF-κB activation and cardiomyocyte hypertrophy has been established previously, our data support the hypothesis that increased O(2)(·-) generation and Akt activation are key signaling intermediates in pressure overload-induced activation of NF-κB and cardiac hypertrophy.

  17. Lack of chemokine signaling through CXCR5 causes increased mortality, ventricular dilatation and deranged matrix during cardiac pressure overload.

    Directory of Open Access Journals (Sweden)

    Anne Waehre

    Full Text Available RATIONALE: Inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF, but a role for chemokines is largely unknown. Based on their role in inflammation and matrix remodeling in other tissues, we hypothesized that CXCL13 and CXCR5 could be involved in cardiac remodeling during HF. OBJECTIVE: We sought to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF. METHODS AND RESULTS: Mice harboring a systemic knockout of the CXCR5 (CXCR5(-/- displayed increased mortality during a follow-up of 80 days after aortic banding (AB. Following three weeks of AB, CXCR5(-/- developed significant left ventricular (LV dilatation compared to wild type (WT mice. Microarray analysis revealed altered expression of several small leucine-rich proteoglycans (SLRPs that bind to collagen and modulate fibril assembly. Protein levels of fibromodulin, decorin and lumican (all SLRPs were significantly reduced in AB CXCR5(-/- compared to AB WT mice. Electron microscopy revealed loosely packed extracellular matrix with individual collagen fibers and small networks of proteoglycans in AB CXCR5(-/- mice. Addition of CXCL13 to cultured cardiac fibroblasts enhanced the expression of SLRPs. In patients with HF, we observed increased myocardial levels of CXCR5 and SLRPs, which was reversed following LV assist device treatment. CONCLUSIONS: Lack of CXCR5 leads to LV dilatation and increased mortality during pressure overload, possibly via lack of an increase in SLRPs. This study demonstrates a critical role of the chemokine CXCL13 and CXCR5 in survival and maintaining of cardiac structure upon pressure overload, by regulating proteoglycans essential for correct collagen assembly.

  18. Lack of chemokine signaling through CXCR5 causes increased mortality, ventricular dilatation and deranged matrix during cardiac pressure overload.

    Science.gov (United States)

    Waehre, Anne; Halvorsen, Bente; Yndestad, Arne; Husberg, Cathrine; Sjaastad, Ivar; Nygård, Ståle; Dahl, Christen P; Ahmed, M Shakil; Finsen, Alexandra V; Reims, Henrik; Louch, William E; Hilfiker-Kleiner, Denise; Vinge, Leif E; Roald, Borghild; Attramadal, Håvard; Lipp, Martin; Gullestad, Lars; Aukrust, Pål; Christensen, Geir

    2011-04-18

    Inflammatory mechanisms have been suggested to play a role in the development of heart failure (HF), but a role for chemokines is largely unknown. Based on their role in inflammation and matrix remodeling in other tissues, we hypothesized that CXCL13 and CXCR5 could be involved in cardiac remodeling during HF. We sought to analyze the role of the chemokine CXCL13 and its receptor CXCR5 in cardiac pathophysiology leading to HF. Mice harboring a systemic knockout of the CXCR5 (CXCR5(-/-)) displayed increased mortality during a follow-up of 80 days after aortic banding (AB). Following three weeks of AB, CXCR5(-/-) developed significant left ventricular (LV) dilatation compared to wild type (WT) mice. Microarray analysis revealed altered expression of several small leucine-rich proteoglycans (SLRPs) that bind to collagen and modulate fibril assembly. Protein levels of fibromodulin, decorin and lumican (all SLRPs) were significantly reduced in AB CXCR5(-/-) compared to AB WT mice. Electron microscopy revealed loosely packed extracellular matrix with individual collagen fibers and small networks of proteoglycans in AB CXCR5(-/-) mice. Addition of CXCL13 to cultured cardiac fibroblasts enhanced the expression of SLRPs. In patients with HF, we observed increased myocardial levels of CXCR5 and SLRPs, which was reversed following LV assist device treatment. Lack of CXCR5 leads to LV dilatation and increased mortality during pressure overload, possibly via lack of an increase in SLRPs. This study demonstrates a critical role of the chemokine CXCL13 and CXCR5 in survival and maintaining of cardiac structure upon pressure overload, by regulating proteoglycans essential for correct collagen assembly.

  19. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

    Science.gov (United States)

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

    2017-07-18

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher ( p coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold ( p coconut oil mice than in standard chow mice. Myocardial capillary density ( p coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold ( p coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower ( p coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  20. Quantitative phosphoproteomic study of pressure-overloaded mouse heart reveals dynamin-related protein 1 as a modulator of cardiac hypertrophy.

    Science.gov (United States)

    Chang, Yu-Wang; Chang, Ya-Ting; Wang, Qinchuan; Lin, Jim Jung-Ching; Chen, Yu-Ju; Chen, Chien-Chang

    2013-11-01

    Pressure-overload stress to the heart causes pathological cardiac hypertrophy, which increases the risk of cardiac morbidity and mortality. However, the detailed signaling pathways induced by pressure overload remain unclear. Here we used phosphoproteomics to delineate signaling pathways in the myocardium responding to acute pressure overload and chronic hypertrophy in mice. Myocardial samples at 4 time points (10, 30, 60 min and 2 weeks) after transverse aortic banding (TAB) in mice underwent quantitative phosphoproteomics assay. Temporal phosphoproteomics profiles showed 360 phosphorylation sites with significant regulation after TAB. Multiple mechanical stress sensors were activated after acute pressure overload. Gene ontology analysis revealed differential phosphorylation between hearts with acute pressure overload and chronic hypertrophy. Most interestingly, analysis of the cardiac hypertrophy pathway revealed phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (DRP1) by prohypertrophic kinases. Phosphorylation of DRP1 S622 was confirmed in TAB-treated mouse hearts and phenylephrine (PE)-treated rat neonatal cardiomyocytes. TAB-treated mouse hearts showed phosphorylation-mediated mitochondrial translocation of DRP1. Inhibition of DRP1 with the small-molecule inhibitor mdivi-1 reduced the TAB-induced hypertrophic responses. Mdivi-1 also prevented PE-induced hypertrophic growth and oxygen consumption in rat neonatal cardiomyocytes. We reveal the signaling responses of the heart to pressure stress in vivo and in vitro. DRP1 may be important in the development of cardiac hypertrophy.

  1. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

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    Tim Peters

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

  2. ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage.

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    Sato, Teruki; Sato, Chitose; Kadowaki, Ayumi; Watanabe, Hiroyuki; Ho, Lena; Ishida, Junji; Yamaguchi, Tomokazu; Kimura, Akinori; Fukamizu, Akiyoshi; Penninger, Josef M; Reversade, Bruno; Ito, Hiroshi; Imai, Yumiko; Kuba, Keiji

    2017-06-01

    Elabela/Toddler/Apela (ELA) has been identified as a novel endogenous peptide ligand for APJ/Apelin receptor/Aplnr. ELA plays a crucial role in early cardiac development of zebrafish as well as in maintenance of self-renewal of human embryonic stem cells. Apelin was the first identified APJ ligand, and exerts positive inotropic heart effects and regulates the renin-angiotensin system. The aim of this study was to investigate the biological effects of ELA in the cardiovascular system. Continuous infusion of ELA peptide significantly suppressed pressure overload-induced cardiac hypertrophy, fibrosis and impaired contractility in mice. ELA treatment reduced mRNA expression levels of genes associated with heart failure and fibrosis. The cardioprotective effects of ELA were diminished in APJ knockout mice, indicating that APJ is the key receptor for ELA in the adult heart. Mechanistically, ELA downregulated angiotensin-converting enzyme (ACE) expression in the stressed hearts, whereas it showed little effects on angiotensin-converting enzyme 2 (ACE2) expression, which are distinct from the effects of Apelin. FoxM1 transcription factor, which induces ACE expression in the stressed hearts, was downregulated by ELA but not by Apelin. ELA antagonized angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. The ELA-APJ axis protects from pressure overload-induced heart failure possibly via suppression of ACE expression and pathogenic angiotensin II signalling. The different effects of ELA and Apelin on the expression of ACE and ACE2 implicate fine-tuned mechanisms for a ligand-induced APJ activation and downstream signalling.

  3. Postoperative Fluid Overload is a Useful Predictor of the Short-Term Outcome of Renal Replacement Therapy for Acute Kidney Injury After Cardiac Surgery.

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    Xu, Jiarui; Shen, Bo; Fang, Yi; Liu, Zhonghua; Zou, Jianzhou; Liu, Lan; Wang, Chunsheng; Ding, Xiaoqiang; Teng, Jie

    2015-08-01

    To analyze the predictive value of postoperative percent fluid overload (PFO) of renal replacement therapy (RRT) for acute kidney injury (AKI) patients after cardiac surgery.Data from 280 cardiac surgery patients between 2005 January and 2012 April were collected for retrospective analyses. A receiver operating characteristic (ROC) curve was used to compare the predictive values of cumulative PFO at different times after surgery for 90-day mortality.The cumulative PFO before RRT initiation was 7.9% ± 7.1% and the median PFO 6.1%. The cumulative PFO before and after RRT initiation in intensive care unit (ICU) was higher in the death group than in the survival group (8.8% ± 7.6% vs 6.1% ± 5.6%, P = 0.001; -0.5[-5.6, 5.1]% vs 6.9[2.2, 14.6]%, P 731, and 0.752. PFO during the whole ICU stay ≥7.2% was determined as the cut-off point for 90-day mortality prediction with a sensitivity of 77% and a specificity of 64%. Kaplan-Meier survival estimates showed a significant difference in survival among patients with cumulative PFO ≥ 7.2% and PFO < 7.2% after cardiac surgery (log-rank P < 0.001).Postoperative cumulative PFO during the whole ICU stay ≥7.2% would have an adverse effect on 90-day short-term outcome, which may provide a strategy for the volume control of AKI-RRT patients after cardiac surgery.

  4. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction.

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    Chen, Ailan; Li, Wanglin; Chen, Xinyu; Shen, Yuechun; Dai, Wenjun; Dong, Qi; Li, Xinchun; Ou, Caiwen; Chen, Minsheng

    2016-11-17

    Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling. A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated. Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors. Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance

  5. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

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    Ilayaraja Muthuramu

    2017-07-01

    Full Text Available Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05 in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64 during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01 higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001 was decreased, interstitial fibrosis was 1.88-fold (p < 0.001 higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001 higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05 in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  6. Peritoneal Dialysis vs Furosemide for Prevention of Fluid Overload in Infants After Cardiac Surgery: A Randomized Clinical Trial.

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    Kwiatkowski, David M; Goldstein, Stuart L; Cooper, David S; Nelson, David P; Morales, David L S; Krawczeski, Catherine D

    2017-04-01

    Fluid overload after congenital heart surgery is frequent and a major cause of morbidity and mortality among infants. Many programs have adopted the use of peritoneal dialysis (PD) for fluid management; however, its benefits compared with those of traditional diuretic administration are unknown. To determine whether infants randomized to PD vs furosemide for the treatment of oliguria have a higher incidence of negative fluid balance on postoperative day 1, as well as avoidance of 10% fluid overload; shorter duration of mechanical ventilation, intensive care unit stay, and inotrope use; and fewer electrolyte abnormalities. This single-center, unblinded, randomized clinical trial compared methods of fluid removal after cardiac surgery from October 1, 2011, through March 13, 2015, in a large tertiary pediatric hospital in Ohio. The parents or guardians of all eligible infants (aged furosemide (1 mg/kg every 6 hours) or a standardized PD regimen. The primary end point was incidence of negative fluid balance on postoperative day 1. Secondary end points included incidence of fluid overload, duration of mechanical ventilation and intensive care unit stay, electrolyte abnormalities and repletion doses, duration of inotropic administration, and mortality. Seventy-three patients (47 boys [64%] and 26 girls [35%]; median age, 8 [interquartile range (IQR), 6-14] days) received treatment and completed the trial. No difference was found between the PD and furosemide groups in the incidence of negative fluid balance on the first postoperative day. The furosemide group was 3 times more likely to have 10% fluid overload (odds ratio [OR], 3.0; 95% CI, 1.3-6.9), was more likely to have prolonged ventilator use (OR, 3.1; 95% CI, 1.2-8.2), and had a longer duration of inotrope use (median, 5.5 [IQR, 4-8] vs 4.0 [IQR, 3-6] days) and higher electrolyte abnormality scores (median, 6 [IQR, 4-7] vs 3 [IQR, 2-5]) compared with the PD group. No statistically significant differences in

  7. Electrophysiological characteristics of pressure overload-induced cardiac hypertrophy and its influence on ventricular arrhythmias.

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    Chen, Xiaowei; Qin, Mu; Jiang, Weifeng; Zhang, Yu; Liu, Xu

    2017-01-01

    To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias. Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs) and the effective refractory period (ERP) at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES) and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles) as well as the channels' properties of steady-state inactivation and recovery from inactivation. The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P cardiac hypertrophy, and the spatially heterogeneous changes of the channels may increase the occurrence of ventricular arrhythmias that accompany cardiac hypertrophy.

  8. The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

    Science.gov (United States)

    Higashikuni, Yasutomi; Sainz, Julie; Nakamura, Kazuto; Takaoka, Minoru; Enomoto, Soichiro; Iwata, Hiroshi; Tanaka, Kimie; Sahara, Makoto; Hirata, Yasunobu; Nagai, Ryozo; Sata, Masataka

    2012-03-01

    ATP-binding cassette transporter subfamily G member 2 (ABCG2), expressed in microvascular endothelial cells in the heart, has been suggested to regulate several tissue defense mechanisms. This study was performed to elucidate its role in pressure overload-induced cardiac hypertrophy. Pressure overload was induced in 8- to 12-week-old wild-type and Abcg2-/- mice by transverse aortic constriction (TAC). Abcg2-/- mice showed exaggerated cardiac hypertrophy and ventricular remodeling after TAC compared with wild-type mice. In the early phase after TAC, functional impairment in angiogenesis and antioxidant response in myocardium was found in Abcg2-/- mice. In vitro experiments demonstrated that ABCG2 regulates transport of glutathione, an important endogenous antioxidant, from microvascular endothelial cells. Besides, glutathione transported from microvascular endothelial cells in ABCG2-dependent manner ameliorated oxidative stress-induced cardiomyocyte hypertrophy. In vivo, glutathione levels in plasma and the heart were increased in wild-type mice but not in Abcg2-/- mice after TAC. Treatment with the superoxide dismutase mimetic ameliorated cardiac hypertrophy in Abcg2-/- mice after TAC to the same extent as that in wild-type mice, although cardiac dysfunction with impaired angiogenesis was observed in Abcg2-/- mice. ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.

  9. Detection of cardiac iron overload with native magnetic resonance T1 and T2 mapping in patients with thalassemia.

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    Krittayaphong, Rungroj; Zhang, Shuo; Saiviroonporn, Pairash; Viprakasit, Vip; Tanapibunpon, Prajak; Komoltri, Chulaluk; Wangworatrakul, Wipaporn

    2017-12-01

    To investigate the diagnostic performance of native cardiac magnetic resonance (CMR) T1 and T2 mapping for cardiac iron overload (CIO) in thalassemia patients. All thalassemia patients who underwent CMR were enrolled on a clinical 1.5T scanner. Native T1 mapping with the Modified Look-Locker Inversion recovery (MOLLI) technique, T2 mapping using a black-blood multi-echo spin-echo technique, and conventional T2* mapping using multi-echo gradient-echo techniques were performed. CIO was defined by a T2* of T1 and T2 times were significant different among patients with no CIO, mild-to-moderate CIO, and severe CIO (1012.7±57.7 vs. 846.4±34.4 vs 601.3±34.6ms for T1, pT1 and T2, respectively. This yielded a sensitivity, specificity and area under the curve (AUC) of 100%, 98.4% and 0.997 respectively for T1, in comparison to 100%, 88.8% and 0.961 respectively for T2. Native T1 mapping can differentiate between severe, mild-to-moderate, and no CIO, which appears to be a promising technique for detection and assessment of myocardial iron. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure overload.

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    Anna N Panek

    Full Text Available Connective tissue growth factor (CTGF is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG. To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca(2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls.Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF's profibrotic function in the heart.

  11. Employment of vasopressin receptor antagonists in management of hyponatraemia and volume overload in some clinical conditions.

    Science.gov (United States)

    Urso, C; Brucculeri, S; Caimi, G

    2015-08-01

    Hyponatraemia, the most common electrolyte imbalance occurring in hospitalized subjects, is usually classified as hypovolaemic, euvolaemic or hypervolaemic. Hyponatraemia is a predictor of death among subjects with chronic heart failure and cirrhosis. The inappropriate secretion of the antidiuretic hormone (AVP) seems to be of pivotal importance in the decline of serum sodium concentration in these clinical conditions. The objective of this review was to summarize recent progress in management of hyponatraemia in SIADH, cirrhosis and heart failure. Literature searches were conducted on the topics of hyponatraemia and vasopressin receptor antagonists, using PubMed, pharmaceutical company websites and news reports. The information was evaluated for relevance and quality, critically assessed and summarized. The initial treatment of severe hyponatraemia is directed towards the prevention or management of neurological manifestations and consists of an intravenous infusion of hypertonic saline. Fluid restriction is indicated in oedematous states. Diuretics alone or in combination with other specific drugs remain the main strategy in the management of volume overload in heart failure. In resistant cases, ultrafiltration can lead to effective removal of isotonic fluid preventing new episodes of decompensation; however, aquapheresis is associated with increased costs and other limits. In several trials, the efficacy of vasopressin receptor antagonists in euvolaemic patients (inappropriate antidiuretic hormone secretion) or in hypervolaemic hyponatraemia (chronic heart failure, cirrhosis) has been evaluated. It was found that vaptans, which promote aquaresis, were superior to a placebo in raising and maintaining serum sodium concentrations in these subjects. Combined with conventional therapy, vasopressin receptor antagonists (AVP-R antagonists) are able to increase the excretion of electrolyte-free water and the sodium concentration. Further studies are needed to assess

  12. 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

  13. Electrophysiological characteristics of pressure overload-induced cardiac hypertrophy and its influence on ventricular arrhythmias.

    Directory of Open Access Journals (Sweden)

    Xiaowei Chen

    Full Text Available To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias.Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation. Using the Langendorff method of isolated heart perfusion, monophasic action potentials (MAPs and the effective refractory period (ERP at different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles were measured, and the induction rate of ventricular tachyarrhythmias was observed under programmed electrical stimulus (PES and burst stimulus. Whole-cell patch-clamp was used to obtain the I-V characteristics of voltage-gated potassium channels in cardiomyocytes of different parts of the heart (including the epi- and endo-myocardium of the left and right ventricles as well as the channels' properties of steady-state inactivation and recovery from inactivation.The ratio of heart weight to body weight and the ratio of left ventricular weight to body weight in the surgery group were significantly higher than those in the control group (P < 0.05. Ultrasonic evaluation revealed that both interventricular septal diameter (IVSD and left ventricle posterior wall diameter (LVPWD in the surgery group were significantly larger than those in the control group (P < 0.05. Under PES and burst stimuli, the induction rates of arrhythmias in the surgery group significantly increased, reaching 41.2% and 23.5%, respectively. Both the QT interval and action potential duration (APD in the surgery group were significantly longer than in the control group (P<0.01, and the changes showed obvious spatial heterogeneity. Whole-cell patch-clamp recordings demonstrated that the surgery group

  14. Intravascular Volume Profiles in Patients with Class I and II Systolic Heart Failure: Heterogeneity and Volume Overload are Common Even in Mild Heart Failure.

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    Miller, Wayne L; Albers, Diana P; Gansen, Denise N; Mullan, Brian P

    2017-10-02

    While volume overload is a commonly described clinical feature of advanced heart failure (HF), less is known regarding volume profiles of patients with less severe Class I and II HF. Intravascular volume was quantitated by radiolabeled-albumin indicator-dilution technique in clinic out-patients. Forty-six patients [age 61±13 yrs., LVEF 30±8%] were prospectively evaluated with 28 undergoing repeat evaluations at one year. There was no difference in averaged total blood volume (TBV) at baseline between Class I (N=26) and II (N=20) patients (5.6±1.6 vs 6.0±1.3 L, p=0.368) and at one year of follow-up. However, there was marked heterogeneity in plasma volume (-13% to +69% of normal) and red cell mass (RBCM -31% to +50%) profiles with TBV expansion identified in 46% of the cohort while only 48% had a normal TBV. RBCM deficit (true anemia) was common (39%), but a low hemoglobin concentration was accurate in identifying anemia in only 11% of the cohort. RBCM excess (polycythemia) also was identified in 20% of the cohort. Marked heterogeneity in PV and RBCM volume profiles is present even in mild HF and identifying volume overload which was common in early HF has the potential to help guide therapy in the reduction of HF progression. Intravascular volume as a modifiable risk factor in early HF warrants further study. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Extracellular Volume Overload and Increased Vasoconstriction in Patients With Recurrent Intradialytic Hypertension

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    Peter Noel Van Buren

    2016-11-01

    Full Text Available Background/Aims: Intradialytic hypertension (IH occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. Methods: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW and extracellular water (ECW, as well as cardiac index (CI and total peripheral resistance index (TPRI. Results: The ECW/TBW was 0.453 (0.05 pre-dialysis and 0.427 (0.04 post-dialysis in controls vs. 0.478 (0.03 and 0.461 (0.03 in IH patients (p=0.01 post-dialysis. The ECW/TBW change was -0.027 (0.03 in controls and -0.013 (0.02 in IH patients (p=0.1. In controls, pre- and post-dialysis TPRI were 3254 (994 and 2469 (529 dynes/sec/cm2/m2 vs. 2983 (747 and 3408 (980 dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis. There were between-group differences in TPRI change (0=0.0001, but not CI (p=0.09. Conclusions: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.

  16. 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

  17. Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure.

    Science.gov (United States)

    Ebrahim, Barkoudah; Sindhura, Kodali; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

    2015-05-01

    Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): -2.65 to -0.91 kg; p diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = -0.25 mg/dL; 95% CI: -0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64-1.56; p = 0.993). Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

  18. Moderate exercise training improves survival and ventricular remodeling in an animal model of left ventricular volume overload.

    Science.gov (United States)

    Lachance, Dominic; Plante, Eric; Bouchard-Thomassin, Andrée-Anne; Champetier, Serge; Roussel, Elise; Drolet, Marie-Claude; Arsenault, Marie; Couet, Jacques

    2009-09-01

    Exercise training has beneficial effects in patients with heart failure, although there is still no clear evidence that it may impact on their survival. There are no data regarding the effects of exercise in subjects with chronic left ventricular (LV) volume overload. Using a rat model of severe aortic valve regurgitation (AR), we studied the effects of long-term exercise training on survival, development of heart failure, and LV myocardial remodeling. One hundred sixty male adult rats were divided in 3 groups: sham sedentary (n=40), AR sedentary (n=80), and AR trained (n=40). Training consisted in treadmill running for up to 30 minutes, 5 times per week for 9 months, at a maximal speed of 20 m/minute. All sham-operated animals survived the entire course of the protocol. After 9 months, 65% of trained animals were alive compared with 46% of sedentary ones (P=0.05). Ejection fractions remained in the normal range (all above 60%) and LV masses between AR groups were similar. There was significantly less LV fibrosis in the trained group and lower LV filling pressures and improved echocardiographic diastolic parameters. Heart rate variability was also improved by exercise. Our data show that moderate endurance training is safe, does not increase the rate of developing heart failure, and most importantly, improves survival in this animal model of chronic LV volume overload. Exercise improved LV diastolic function, heart rate variability, and reduced myocardial fibrosis.

  19. Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy.

    Science.gov (United States)

    Zhang, Liyan; Jaswal, Jagdip S; Ussher, John R; Sankaralingam, Sowndramalingam; Wagg, Cory; Zaugg, Michael; Lopaschuk, Gary D

    2013-09-01

    Cardiac hypertrophy is accompanied by significant alterations in energy metabolism. Whether these changes in energy metabolism precede and contribute to the development of heart failure in the hypertrophied heart is not clear. Mice were subjected to cardiac hypertrophy secondary to pressure-overload as a result of an abdominal aortic constriction (AAC). The rates of energy substrate metabolism were assessed in isolated working hearts obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a progressive development of cardiac hypertrophy. In vivo assessment of cardiac function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks (20% increase in E/E'), and systolic dysfunction by 3 weeks (16% decrease in % ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was evidenced by a significant decrease in insulin-stimulated rates of glycolysis and glucose oxidation, and plasma membrane translocation of glucose transporter 4. Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and 47%, respectively) because of a reduction in mitochondrial oxidation of glucose, lactate, and fatty acids that was not accompanied by an increase in myocardial glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP. The development of cardiac insulin-resistance and decreased mitochondrial oxidative metabolism are early metabolic changes in the development of cardiac hypertrophy, which create an energy deficit that may contribute to the progression from hypertrophy to heart failure.

  20. Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

    Science.gov (United States)

    Fukunami, Masatake; Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru

    2011-12-01

    Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

  1. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    National Research Council Canada - National Science Library

    Ilayaraja Muthuramu; Ruhul Amin; Andrey Postnov; Mudit Mishra; Frank Jacobs; Olivier Gheysens; Paul P. Van Veldhoven; Bart De Geest

    2017-01-01

    .... We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice...

  2. Assessment of cardiac function and hemodynamics in children and adults with right ventricular pressure overload: role of cardiac magnetic resonance imaging

    NARCIS (Netherlands)

    Romeih, Soha

    2014-01-01

    Accumulating evidence suggests that pressure overload on the right ventricle (RV) leads to RV dysfunction, with considerable morbidity and mortality. Therefore, appropriate RV evaluation is essential because timely intervention may preserve RV function and prevent irreversible RV damage. Currently,

  3. Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2017-07-01

    Full Text Available Background/Aims: An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB, extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Methods: Mice received aortic banding (AB operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/SH, sham+NOB (NOB/SH, AB+vehicle (VEH/AB, and AB+ NOB (NOB/AB. Animals (n = 15 per group were treated with vehicle or NOB (50 mg/kg for 4 weeks after disease onset. Results: NOB prevented cardiac hypertrophy induced by aortic banding (AB, as assessed by the cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers and cardiac function. In addition, NOB supplementation blunted the increased expression of NAPDH oxidase (NOX 2 and NOX4 and mitigated endoplasmic reticulum (ER stress and myocyte apoptosis in cardiac hypertrophy. Furthermore, NOB treatment attenuated the neonatal rat cardiomyocyte (NRCM hypertrophic response stimulated by phenylephrine (PE and alleviated ER stress. However, our data showed that NOB dramatically inhibited NOX2 expression but not NOX4 in vitro. Finally, we found that knockdown of NOX2 attenuated ER stress in NRCMs stimulated by PE. Conclusions: Inhibition of oxidative and ER stress by NOB in the myocardium may represent a potential therapy for cardiac hypertrophy. Moreover, there is a direct role of NOX2 in regulating ER stress stimulated by PE.

  4. Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Zhang, Ning; Wei, Wen-Ying; Yang, Zheng; Che, Yan; Jin, Ya-Ge; Liao, Hai-Han; Wang, Sha-Sha; Deng, Wei; Tang, Qi-Zhu

    2017-01-01

    An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/SH), sham+NOB (NOB/SH), AB+vehicle (VEH/AB), and AB+ NOB (NOB/AB). Animals (n = 15 per group) were treated with vehicle or NOB (50 mg/kg) for 4 weeks after disease onset. NOB prevented cardiac hypertrophy induced by aortic banding (AB), as assessed by the cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers and cardiac function. In addition, NOB supplementation blunted the increased expression of NAPDH oxidase (NOX) 2 and NOX4 and mitigated endoplasmic reticulum (ER) stress and myocyte apoptosis in cardiac hypertrophy. Furthermore, NOB treatment attenuated the neonatal rat cardiomyocyte (NRCM) hypertrophic response stimulated by phenylephrine (PE) and alleviated ER stress. However, our data showed that NOB dramatically inhibited NOX2 expression but not NOX4 in vitro. Finally, we found that knockdown of NOX2 attenuated ER stress in NRCMs stimulated by PE. Inhibition of oxidative and ER stress by NOB in the myocardium may represent a potential therapy for cardiac hypertrophy. Moreover, there is a direct role of NOX2 in regulating ER stress stimulated by PE. © 2017 The Author(s). Published by S. Karger AG, Basel.

  5. Changes in T-Tubules and Sarcoplasmic Reticulum in Ventricular Myocytes in Early Cardiac Hypertrophy in a Pressure Overload Rat Model

    Directory of Open Access Journals (Sweden)

    Perla Pérez-Treviño

    2015-10-01

    Full Text Available Background/Aims: Pressure-overload (PO causes cardiac hypertrophy (CH, and eventually leads to heart failure (HF. HF ventricular myocytes present transverse-tubules (TT loss or disarrangement and decreased sarcoplasmic reticulum (SR density, and both contribute to altered Ca2+ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH. Methods: Using confocal microscopy, we assessed TT (with Di-8-ANNEPS and SR (with SR-trapped Mag-Fluo-4 densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP, cytosolic Ca2+ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks. Results: Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca2+ signaling and SR Ca2+ content were unaltered. Conclusion: SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca2+ signaling and contractility.

  6. Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure.

    Science.gov (United States)

    Gesmundo, Iacopo; Miragoli, Michele; Carullo, Pierluigi; Trovato, Letizia; Larcher, Veronica; Di Pasquale, Elisa; Brancaccio, Mara; Mazzola, Marta; Villanova, Tania; Sorge, Matteo; Taliano, Marina; Gallo, Maria Pia; Alloatti, Giuseppe; Penna, Claudia; Hare, Joshua M; Ghigo, Ezio; Schally, Andrew V; Condorelli, Gianluigi; Granata, Riccarda

    2017-11-07

    It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH 2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gα s and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy. Copyright © 2017 the Author(s). Published by PNAS.

  7. Cardiac filling volumes versus pressures for predicting fluid responsiveness after cardiovascular surgery: the role of systolic cardiac function

    NARCIS (Netherlands)

    Trof, Ronald J.; Danad, Ibrahim; Reilingh, Mikel W. L.; Breukers, Rose-Marieke Bge; Groeneveld, Ab Johan

    2011-01-01

    ABSTRACT: INTRODUCTION: Static cardiac filling volumes have been suggested to better predict fluid responsiveness than filling pressures, but this may not apply to hearts with systolic dysfunction and dilatation. We evaluated the relative value of cardiac filling volume and pressures for predicting

  8. 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.

  9. Right ventricular failure secondary to chronic overload in congenital heart diseases: benefits of cell therapy using human embryonic stem cell-derived cardiac progenitors.

    Science.gov (United States)

    Lambert, Virginie; Gouadon, Elodie; Capderou, André; Le Bret, Emmanuel; Ly, Mohamed; Dinanian, Sylvie; Renaud, Jean-Francois; Pucéat, Michel; Rücker-Martin, Catherine

    2015-03-01

    Despite the increasing incidence of right ventricular (RV) failure in adult patients with congenital heart disease, current therapeutic options are still limited. By contrast to left-heart diseases, cell-based myocardial regeneration applied to the right ventricle is poorly studied, even though it may be a therapeutic solution. As human embryonic stem cell-derived cardiac progenitors seem to be good candidates owing to their proliferation capacity, our aim was to assess, in a large animal model of overloaded RV dysfunction, the feasibility and effects of such a cell therapy. Human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells were administered using multiple intramyocardial injections 4 months after a surgical procedure mimicking the repaired tetralogy of Fallot, and their effects were observed 3 months later on hemodynamic, rhythmic, and histologic parameters. All pigs (sham n = 6, treated n = 6) survived without complication, and cell therapy was clinically well tolerated. Although functional, contractility, and energetics parameters evolved similarly in both groups, benefits regarding arrhythmic susceptibility were observed in the treated group, associated with a significant decrease of peri-myocyte fibrosis (5.71% ± 2.49% vs 12.12% ± 1.85%; P cells could be detected within the myocardium. Cell therapy using intramyocardial injections of human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV tissue remodeling and arrhythmic susceptibility, but this mode of administration is not sufficient to obtain a significant improvement in RV function. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  10. The primary benefits of angiotensin-converting enzyme inhibition on cardiac remodeling occur during sleep time in murine pressure overload hypertrophy.

    Science.gov (United States)

    Martino, Tami A; Tata, Nazneen; Simpson, Jeremy A; Vanderlaan, Rachel; Dawood, Fayez; Kabir, M Golam; Khaper, Neelam; Cifelli, Carlo; Podobed, Peter; Liu, Peter P; Husain, Mansoor; Heximer, Scott; Backx, Peter H; Sole, Michael J

    2011-05-17

    Our objective was to test the hypothesis that there is a significant diurnal variation for the therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors on pressure-overload cardiovascular hypertrophy. Physiological and molecular processes exhibit diurnal rhythms that may affect efficacy of disease treatment (chronotherapy). Evidence suggests that the heart primarily remodels during sleep. Although a growing body of clinical and epidemiological evidence suggests that the timing of therapy, such as ACE inhibition, alters diurnal blood pressure patterns in patients with hypertension, the benefits of chronotherapy on myocardial and vascular remodeling have not been studied. We examined the effects of the short-acting ACE inhibitor, captopril, on the structure and function of cardiovascular tissue subjected to pressure overload by transverse aortic constriction (TAC) in mice. Captopril (15 mg/kg intraperitoneally) or placebo was administered at either murine sleep time or wake time for 8 weeks starting 1 week after surgery. TAC mice given captopril at sleep time had improved cardiac function and significantly decreased heart: body weight ratios, myocyte cross-sectional areas, intramyocardial vascular medial wall thickness, and perivascular collagen versus TAC mice given captopril or placebo during wake time. Captopril induced similar drops in blood pressure at sleep or wake time, suggesting that time-of-day differences were not attributable to blood pressure changes. These beneficial effects of captopril were correlated with diurnal changes in ACE mRNA expression in the heart. The ACE inhibitor captopril benefited cardiovascular remodeling only when administered during sleep; wake-time captopril ACE inhibition was identical to that of placebo. These studies support the hypothesis that the heart (and vessels) remodel during sleep time and also illustrate the importance of diurnal timing for some cardiovascular therapies. Copyright © 2011 American College of

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

    Science.gov (United States)

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

    2017-01-01

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

  12. The overloaded right heart and ventricular interdependence.

    Science.gov (United States)

    Naeije, Robert; Badagliacca, Roberto

    2017-10-01

    The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights

  13. The autocrine role of tryptase in pressure overload-induced mast cell activation, chymase release and cardiac fibrosis

    Directory of Open Access Journals (Sweden)

    Jianping Li

    2016-03-01

    Results and conclusion: The results indicate the presence of PAR-2 on MCs and that tryptase inhibition and nedocromil prevented TAC-induced fibrosis and increases in MC density, activation, and chymase release. Tryptase also significantly increased chymase concentration in ventricular slice culture media, which was prevented by the tryptase inhibitor. Hydroxyproline concentration in culture media was significantly increased with tryptase incubation as compared to the control group and the tryptase group incubated with nafamostat mesilate or chymostatin. We conclude that tryptase contributes to TAC-induced cardiac fibrosis primarily via activation of MCs and the amplified release of chymase.

  14. Goal-Directed Fluid Therapy Using Stroke Volume Variation Does Not Result in Pulmonary Fluid Overload in Thoracic Surgery Requiring One-Lung Ventilation

    Directory of Open Access Journals (Sweden)

    Sebastian Haas

    2012-01-01

    Full Text Available Background. Goal-directed fluid therapy (GDT guided by functional parameters of preload, such as stroke volume variation (SVV, seems to optimize hemodynamics and possibly improves clinical outcome. However, this strategy is believed to be rather fluid aggressive, and, furthermore, during surgery requiring thoracotomy, the ability of SVV to predict volume responsiveness has raised some controversy. So far it is not known whether GDT is associated with pulmonary fluid overload and a deleterious reduction in pulmonary function in thoracic surgery requiring one-lung-ventilation (OLV. Therefore, we assessed the perioperative course of extravascular lung water index (EVLWI and paO2/FiO2-ratio during and after thoracic surgery requiring lateral thoracotomy and OLV to evaluate the hypothesis that fluid therapy guided by SVV results in pulmonary fluid overload. Methods. A total of 27 patients (group T were enrolled in this prospective study with 11 patients undergoing lung surgery (group L and 16 patients undergoing esophagectomy (group E. Goal-directed fluid management was guided by SVV (SVV 0.05 in EVLWI during the observation period (BL: 7.8 ± 2.5, 24postop: 8.1 ± 2.4 mL/kg. A subgroup analysis for group L and group E also did not reveal significant changes of EVLWI. The paO2/FiO2-ratio decreased significantly during the observation period (group L: BL: 462 ± 140, OLVterm15: 338 ± 112 mmHg; group E: BL: 389 ± 101, 24postop: 303 ± 74 mmHg but remained >300 mmHg except during OLV. Conclusions. SVV-guided fluid management in thoracic surgery requiring lateral thoracotomy and one-lung ventilation does not result in pulmonary fluid overload. Although oxygenation was reduced, pulmonary function remained within a clinically acceptable range.

  15. Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

    Science.gov (United States)

    Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

    2011-12-01

    Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

  16. Dietary omega-3 polyunsaturated fatty acids suppress NHE-1 upregulation in a rabbit model of volume- and pressure-overload

    NARCIS (Netherlands)

    van Borren, Marcel M. G. J.; den Ruijter, Hester M.; Baartscheer, Antonius; Ravesloot, Jan H.; Coronel, Ruben; Verkerk, Arie O.

    2012-01-01

    Background: Increased consumption of omega-3 polyunsaturated fatty acids (omega 3-PUFAs) from fish oil (FO) may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HE). The cardiac Na+/H+-exchanger (NHE-1) is a key mediator for these detrimental cardiac

  17. Potential impact of cardiac dose-volume on acute cardiac toxicity following concurrent trastuzumab and radiotherapy.

    Science.gov (United States)

    Cao, L; Hu, W G; Kirova, Y M; Yang, Z Z; Cai, G; Yu, X L; Ma, J L; Guo, X M; Shao, Z M; Chen, J Y

    2014-03-01

    To analyse the risk factors associated with acute cardiotoxicity in HER2-positive breast cancer patients receiving concurrent trastuzumab and radiotherapy. Medical records of 45 breast cancer patients treated between 02/2009 and 02/2011 by concurrent trastuzumab and radiotherapy were collected. Radiation was delivered to the conserved breast or chest wall with or without regional nodes. Dose prescription was 50Gy in 25 fractions over five weeks with a tumor bed boost of 10Gy in 5 fractions in breast conservation. Acute cardiotoxicity (grade≥1) was defined using NCI-CTC v2.0. Doses to the heart and left ventricle were quantified. Median follow-up of left ventricular ejection fraction and clinical assessment from the completion of radiotherapy was 10 months (range: 3-27 months) and 25 months (range: 13-40 months), respectively. Ten (22.2%) and one (2.2%) of the 45 patients developed grade 1 and grade 2 cardiotoxicity, respectively. For 24 left-sided patients, the mean heart dose was significantly higher in those with cardiac events compared to those without (10.14 and 6.27Gy, respectively; Pparameters of cardiac structures and cardiac events was found in right-sided patients. Left-sided irradiation with increased low dose-volume and mean heart dose were associated with increased but reversible low-grade early cardiac toxicity after use of concurrent trastuzumab. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  18. Increasing fill volume reduces cardiac performance in peritoneal dialysis

    DEFF Research Database (Denmark)

    Ivarsen, Per; Povlsen, Johan V; Jensen, Jens Dam

    2007-01-01

    the demand on the heart even during normal daily activities. METHODS: Fifteen stable PD patients were included in this randomized, controlled, open-label crossover study. After drainage, we measured blood pressure, pulse rate and cardiac output (CO) after 30 min in the supine position. The measurements were...... arterial blood pressure remained unchanged. In the upright position, SV and CO decreased and total peripheral systemic resistance increased. Pulse rate and mean arterial blood pressure were unchanged independent of fill volume when compared with the drained situation. During postural change, no significant...... repeated 5 min later in an upright position. Subsequently, following fill, the measurements were repeated after 30 min in the supine and 5 min later in the upright position. The two procedures were repeated twice. The fill was either 2 l or 3 l of dialysate. CO was measured with a non-invasive device based...

  19. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2017-01-01

    the often uncritical inclusion of too much data. This paper discusses the general term information overload and its lexicographical counterpart data overload. Different types of data overload are identified and the problems users have when retrieving the necessary information from dictionary articles......Too often online dictionaries still display too many features determined by the restrictions that applied to printed dictionaries. Data overload in dictionary articles can be regarded as one such relic from the past. However, the idea that online dictionaries have unlimited space has furthered...

  20. Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Elise Roussel

    2015-01-01

    Full Text Available Patients with left ventricle (LV volume overload (VO remain in a compensated state for many years although severe dilation is present. The myocardial capacity to fulfill its energetic demand may delay decompensation. We performed a gene expression profile, a model of chronic VO in rat LV with severe aortic valve regurgitation (AR for 9 months, and focused on the study of genes associated with myocardial energetics. Methods. LV gene expression profile was performed in rats after 9 months of AR and compared to sham-operated controls. LV glucose and fatty acid (FA uptake was also evaluated in vivo by positron emission tomography in 8-week AR rats treated or not with fenofibrate, an activator of FA oxidation (FAO. Results. Many LV genes associated with mitochondrial function and metabolism were downregulated in AR rats. FA β-oxidation capacity was significantly impaired as early as two weeks after AR. Treatment with fenofibrate, a PPARα agonist, normalized both FA and glucose uptake while reducing LV dilation caused by AR. Conclusion. Myocardial energy substrate preference is affected early in the evolution of LV-VO cardiomyopathy. Maintaining a relatively normal FA utilization in the myocardium could translate into less glucose uptake and possibly lesser LV remodeling.

  1. Moderate intensity supine exercise causes decreased cardiac volumes and increased outer volume variations: a cardiovascular magnetic resonance study

    DEFF Research Database (Denmark)

    Steding-Ehrenborg, Katarina; Jablonowski, Robert; Arvidsson, Per M

    2013-01-01

    The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study ...... was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR).......The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study...

  2. Effects of volume-based overload plyometric training on maximal-intensity exercise adaptations in young basketball players.

    Science.gov (United States)

    Asadi, Abbas; Ramirez-Campillo, Rodrigo; Meylan, Cesar; Nakamura, Fabio Y; Cañas-Jamett, Rodrigo; Izquierdo, Mikel

    2017-12-01

    The aim of the present study was to compare maximal-intensity exercise adaptations in young basketball players (who were strong individuals at baseline) participating in regular basketball training versus regular plus a volume-based plyometric training program in the pre-season period. Young basketball players were recruited and assigned either to a plyometric with regular basketball training group (experimental group [EG]; N.=8), or a basketball training only group (control group [CG]; N.=8). The athletes in EG performed periodized (i.e., from 117 to 183 jumps per session) plyometric training for eight weeks. Before and after the intervention, players were assessed in vertical and broad jump, change of direction, maximal strength and a 60-meter sprint test. No significant improvements were found in the CG, while the EG improved vertical jump (effect size [ES] 2.8), broad jump (ES=2.4), agility T test (ES=2.2), Illinois agility test (ES=1.4), maximal strength (ES=1.8), and 60-m sprint (ES=1.6) (Ptraining in addition to regular basketball practice can lead to meaningful improvements in maximal-intensity exercise adaptations among young basketball players during the pre-season.

  3. Value of the Electrocardiogram as a Predictor of Right Ventricular Dysfunction in Patients With Chronic Right Ventricular Volume Overload.

    Science.gov (United States)

    Alonso, Pau; Andrés, Ana; Rueda, Joaquín; Buendía, Francisco; Igual, Begoña; Rodríguez, María; Osa, Ana; Arnau, Miguel A; Salvador, Antonio

    2015-05-01

    Pulmonary regurgitation is a common complication in patients with repaired tetralogy of Fallot or congenital pulmonary stenosis. Electrocardiographic variables have been correlated with parameters used to evaluate right ventricular function. We aimed to analyze the diagnostic value of the width and fragmentation of the electrocardiogram in the identification of patients with right ventricular dysfunction and/or dilation. We selected 107 consecutive patients diagnosed with severe pulmonary insufficiency after repair of pulmonary stenosis or tetralogy of Fallot. The tests included electrocardiography, echocardiography, and magnetic resonance. Each electrocardiogram was analyzed manually to measure QRS duration. We defined QRS fragmentation as the presence of low-voltage waves in the terminal portion of the QRS complex in at least 2 contiguous leads. We found a significant negative correlation between QRS width and right ventricular function, as well as a positive correlation with right ventricular volume. The receiver operating characteristic curve indicated a cut-off point for QRS width of 140ms, which showed good sensitivity for a diagnosis of right ventricular dilation (> 80%) and dysfunction (> 95%). In logistic regression models, a QRS duration > 140ms was found to be the only independent predictor of right ventricular dilation and dysfunction. Electrocardiography is a rapid, widely available, and reproducible tool. QRS width constitutes an independent predictor of the presence of right ventricular dilation and dysfunction. This study is the first to provide a cutoff value for QRS width to screen for right ventricle involvement. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload.

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    Konstam, Marvin A; Kiernan, Michael; Chandler, Arthur; Dhingra, Ravi; Mody, Freny Vaghaiwalla; Eisen, Howard; Haught, W Herbert; Wagoner, Lynne; Gupta, Divya; Patten, Richard; Gordon, Paul; Korr, Kenneth; Fileccia, Russell; Pressler, Susan J; Gregory, Douglas; Wedge, Patricia; Dowling, Douglas; Romeling, Matthew; Konstam, Jeremy M; Massaro, Joseph M; Udelson, James E

    2017-03-21

    In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Never in mitosis gene A related kinase-6 attenuates pressure overload-induced activation of the protein kinase B pathway and cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Zhouyan Bian

    Full Text Available Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A-related kinase-6 (Nek6 is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6-/- mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.

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

    Science.gov (United States)

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

    2017-07-01

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

  7. Combination of Urinary Sodium/Creatinine Ratio and Plasma Brain Natriuretic Peptide Level Predicts Successful Tolvaptan Therapy in Patients With Heart Failure and Volume Overload.

    Science.gov (United States)

    Sato, Yuichi; Dohi, Kaoru; Watanabe, Kiyotaka; Tanimura, Muneyoshi; Takeuchi, Tetsushiro; Sugiura, Emiyo; Sugimoto, Tadafumi; Kumagai, Naoto; Ogura, Toru; Nakamori, Shiro; Fujimoto, Naoki; Yamada, Norikazu; Ito, Masaaki

    2016-01-01

    To evaluate the short-term clinical and hemodynamic effects of tolvaptan therapy and to identify predictors of the therapeutic outcomes, we retrospectively recruited 60 consecutive hospitalized heart failure (HF) patients (70 ± 11 years) with volume overload. The subjects were divided into two groups on the basis of the changes in HF symptom scores and hemodynamic status assessed by right heart catheterization after tolvaptan therapy (median: 7 days). The majority of patients were successfully treated (group 1). However, 22% of patients (group 2) were unsuccessfully treated, in whom 1) the HF symptom score worsened or 2) there was a stationary HF symptom score ≥ 6 points, and mean PCWP > 18 mmHg and mean RAP > 10 mmHg, after tolvaptan therapy. HF symptom scores, hemodynamic parameters, and plasma brain natriuretic peptide (BNP) level improved in group 1, but all of these parameters remained unchanged in group 2. Lower urine sodium/creatinine ratio (UNa/UCr) and higher BNP level at baseline were independently associated with unsuccessful tolvaptan therapy, and UNa/UCr best predicts unsuccessful tolvaptan therapy with a cut-off value of 46.5 mEq/g·Cr (AUC 0.847, 95% CI: 0.718-0.976, sensitivity 77%, specificity 81%, P 778 pg/mL predicted unsuccessful tolvaptan therapy with high diagnostic accuracy (sensitivity 54%, specificity 100%, positive predictive value 100%, negative predictive value 89%, and accuracy 90%). In summary, short-term tolvaptan therapy ameliorated HF symptoms and provided hemodynamic improvement in the majority of patients, and UNa/UCr and BNP level strongly predicted the therapeutic outcomes.

  8. Sex differences play a role in cardiac endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis induced by pressure overload and thapsigargin.

    Science.gov (United States)

    Sari, Flori R; Watanabe, Kenichi; Widyantoro, Bambang; Thandavarayan, Rajarajan A; Harima, Meilei; Kodama, Makoto; Aizawa, Yoshifusa

    2011-01-01

    Excessive endoplasmic reticulum stress (ERS) triggers myocardial apoptosis. Sex differences appear to be an important determinant in the occurrence of stress and apoptosis through many pathways, but the roles of sex differences in the cardiac ERS and ERS-initiated apoptosis are largely unknown. In the present study, we investigated the in vivo role of sex differences in the cardiac ERS and apoptosis elicited by ascending aortic banding surgery or thapsigargin (Thap) injection using male and female C57BL/6 JAX mice. The surgery significantly increased the expression levels of cardiac glucose-regulated protein (GRP)78 and CCAAT/enhancer binding protein homology protein (CHOP) protein, increased the myocardial apoptosis and decreased the sarcoplasmic reticulum Ca(2+)-ATPase isoform (SERCA)2 immunoreactivity in the male mice relative to female mice. Furthermore, during ERS induction using Thap, myocardial apoptosis and the expression levels of cardiac GRP78, inositol-requiring enzyme (Ire)1α and tumor necrosis factor receptor-associated factor (TRAF)2 were significantly increased in male mice relative to female mice. Sex differences significantly affected the above results. Our data suggest that sex differences affected the response of myocardial tissues in dealing with cardiac ERS and further result of ERS, apoptosis, at least in part through the regulation of SERCA2, CHOP, Ire1α and TRAF2. Copyright © 2011. Published by Elsevier Inc.

  9. Death by information overload.

    Science.gov (United States)

    Hemp, Paul

    2009-09-01

    The value of information in the knowledge economy is indisputable, but so is its capacity to overwhelm consumers of it. HBR contributing editor Hemp reports on practical ways for individuals and organizations to avoid getting too much of a good thing. Ready access to useful information comes at a cost: As the volume increases, the line between the worthwhile and the distracting starts to blur. And ready access to you--via e-mail, social networking, and so on--exacerbates the situation: On average, Intel executives get 300 e-mails a day, and Microsoft workers need 24 minutes to return to work after each e-mail interruption. Clearly, productivity is taking a hit. Technological aids can help, such as e-mail management software for you, a message-volume regulation system for your organization, or even more-sophisticated solutions being developed by Microsoft, IBM, and others. Yet, battling technological interruptions on their own turf only goes so far. You also need to change your mind-set, perhaps by seeking help from personal-productivity experts or by simply accepting that you can't respond to every distraction that flits across your screen. Similarly, organizations must change their cultures, for instance by establishing clear e-communication protocols. In the end, only a multipronged approach will help you and your organization subdue the multiheaded monster of information overload. The secret is to manage the beast while still respecting it for the beautiful creature it is.

  10. Improved cardiac filling facilitates the postprandial elevation of stroke volume in Python regius.

    Science.gov (United States)

    Enok, Sanne; Leite, Gabriella S P C; Leite, Cléo A C; Gesser, Hans; Hedrick, Michael S; Wang, Tobias

    2016-10-01

    To accommodate the pronounced metabolic response to digestion, pythons increase heart rate and elevate stroke volume, where the latter has been ascribed to a massive and fast cardiac hypertrophy. However, numerous recent studies show that heart mass rarely increases, even upon ingestion of large meals, and we therefore explored the possibility that a rise in mean circulatory filling pressure (MCFP) serves to elevate venous pressure and cardiac filling during digestion. To this end, we measured blood flows and pressures in anaesthetized Python regius The anaesthetized snakes exhibited the archetypal tachycardia as well as a rise in both venous pressure and MCFP that fully account for the approximate doubling of stroke volume. There was no rise in blood volume and the elevated MCFP must therefore stem from increased vascular tone, possibly by means of increased sympathetic tone on the veins. Furthermore, although both venous pressure and MCFP increased during volume loading, there was no evidence that postprandial hearts were endowed with an additional capacity to elevate stroke volume. In vitro measurements of force development of paced ventricular strips also failed to reveal signs of increased contractility, but the postprandial hearts had higher activities of cytochrome oxidase and pyruvate kinase, which probably serves to sustain the rise in cardiac work during digestion. © 2016. Published by The Company of Biologists Ltd.

  11. Mechanical ventilation with high tidal volume and associated mortality in the cardiac intensive care unit.

    Science.gov (United States)

    Shorofsky, Matthew; Jayaraman, Dev; Lellouche, Francois; Husa, Regina; Lipes, Jed

    2014-03-01

    Use of protective ventilation has been shown to decrease mortality in medical-surgical ICUs. There is limited data on tidal volume use in ventilated patients in the cardiac intensive care unit (CICU). We hypothesized that large tidal volumes are used in the CICU and that they could contribute to an increase in morbidity and mortality. We conducted a retrospective chart review of all mechanically ventilated patients with congestive heart failure or cardiac arrest in a single tertiary care CICU between April 2010 and February 2012. Ventilator settings were analyzed and tidal volume for predicted body weight (VT/PBW) was calculated for 51 patients. The median initial tidal volume was 525 ml (IQR: 500-600) and median VT/PBW was 9.3 ml/kg (IQR: 8.3-10.1). Overall mortality was 29.4%. On univariate analysis, patients that received a VT/PBW below the median, mortality was 23.1% (95% CI: 7.9-39.3) compared to 36.0% (95% CI: 17.2-55.0) in patients that received a VT/PBW above themedian (P = 0.31). On multivariate analysis, the OR for death was 9.0 (95% CI: 1.3-62.0, P = 0.03) with VT/PBW above the median. Mechanical ventilation with high tidal volumes was associated with increased mortality in patients with congestive heart failure and post cardiac arrest in our CICU.

  12. Mitochondria in cardiac hypertrophy and heart failure

    Science.gov (United States)

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2013-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenergetics must keep up with the cardiac hypertrophic phenotype. We review data regarding the mitochondrial proteomic and energetic remodeling in cardiac hypertrophy, as well as the temporal and causal relationship between mitochondrial failure to match the increased energy demand and progression to cardiac decompensation. We suggest that the maladaptive effect of sustained neuroendocrine signals on mitochondria leads to bioenergetic fading which contributes to the progression from cardiac hypertrophy to failure. PMID:22982369

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. Fluid Overload and Cumulative Thoracostomy Output Are Associated With Surgical Site Infection After Pediatric Cardiothoracic Surgery.

    Science.gov (United States)

    Sochet, Anthony A; Nyhan, Aoibhinn; Spaeder, Michael C; Cartron, Alexander M; Song, Xiaoyan; Klugman, Darren; Brown, Anna T

    2017-08-01

    To determine the impact of cumulative, postoperative thoracostomy output, amount of bolus IV fluids and peak fluid overload on the incidence and odds of developing a deep surgical site infection following pediatric cardiothoracic surgery. A single-center, nested, retrospective, matched case-control study. A 26-bed cardiac ICU in a 303-bed tertiary care pediatric hospital. Cases with deep surgical site infection following cardiothoracic surgery were identified retrospectively from January 2010 through December 2013 and individually matched to controls at a ratio of 1:2 by age, gender, Risk Adjustment for Congenital Heart Surgery score, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, primary cardiac diagnosis, and procedure. None. Twelve cases with deep surgical site infection were identified and matched to 24 controls without detectable differences in perioperative clinical characteristics. Deep surgical site infection cases had larger thoracostomy output and bolus IV fluid volumes at 6, 24, and 48 hours postoperatively compared with controls. For every 1 mL/kg of thoracostomy output, the odds of developing a deep surgical site infection increase by 13%. By receiver operative characteristic curve analysis, a cutoff of 49 mL/kg of thoracostomy output at 48 hours best discriminates the development of deep surgical site infection (sensitivity 83%, specificity 83%). Peak fluid overload was greater in cases than matched controls (12.5% vs 6%; p analysis, a threshold value of 10% peak fluid overload was observed to identify deep surgical site infection (sensitivity 67%, specificity 79%). Conditional logistic regression of peak fluid overload greater than 10% on the development of deep surgical site infection yielded an odds ratio of 9.4 (95% CI, 2-46.2). Increased postoperative peak fluid overload and cumulative thoracostomy output were associated with deep surgical site infection after pediatric cardiothoracic surgery. We

  15. Estimating cardiac fiber orientations in pig hearts using registered ultrasound and MR image volumes

    Science.gov (United States)

    Dormer, James D.; Meng, Yuguang; Zhang, Xiaodong; Jiang, Rong; Wagner, Mary B.; Fei, Baowei

    2017-03-01

    Heart fiber mechanics can be important predictors in current and future cardiac function. Accurate knowledge of these mechanics could enable cardiologists to provide a diagnosis before conditions progress. Magnetic resonance diffusion tensor imaging (MR-DTI) has been used to determine cardiac fiber orientations. Ultrasound is capable of providing anatomical information in real time, enabling a physician to quickly adjust parameters to optimize image scans. If known fiber orientations from a template heart measured using DTI can be accurately deformed onto a cardiac ultrasound volume, fiber orientations could be estimated for the patient without the need for a costly MR scan while still providing cardiologists valuable information about the heart mechanics. In this study, we apply the method to pig hearts, which are a close representation of human heart anatomy. Experiments from pig hearts show that the registration method achieved an average Dice similarity coefficient (DSC) of 0.819 +/- 0.050 between the ultrasound and deformed MR volumes and that the proposed ultrasound-based method is able to estimate the cardiac fiber orientation in pig hearts.

  16. Influence of genetic polymorphisms and mutations in the cardiac pathology of iron overload in thalassemia and sickle cell anemia patients: a retrospective study

    Directory of Open Access Journals (Sweden)

    Veronica Agrigento

    2012-11-01

    Full Text Available Cardiac disease in thalassemia is determined by the accumulation of iron in the tissue. Genetic factors could influence the severity and the rapidity of the modifications of the cardiac tissue. Mutations or polymorphisms of genes have already been described as being implicated in cardiac disease. In particular, we studied the polymorphisms C1091T in the Connexin 37 gene (CX 37, 4G -668 5G in the Plasminogen Activator Inhibitor-1 gene (PAI 1 and 5A-1171 6A in the Stromelysin-1 gene (SL in 193 randomly selected patients affected by hemoglobinopathies and 100 normal subjects randomly selected from the general population. A retrospective analysis based on history, clinical data and imaging studies was carried out to assess the presence and type of heart disease. The results of our study do not demonstrate a close association between polymorphism in these candidate genes and cardiac disease, and in particular with myocardial infarction in a cohort of Sicilian patients affected by hemoglobinopathies. 地中海贫血心脏病的关键诱因是组织中的铁沉积。遗传因子可能影响心脏组织修复的严重程度和速度。基因突变或基因多态性与心脏病有关。尤其是,我们研究了193名随机选择的血红蛋白病患者以及从普通人群中随机选择的100名正常受试者的连接蛋白37基因(CX37)的C1091T、纤溶酶原激活物抑制剂-1基因(PAI1)的4G -668 5G 和基质分解素-1基因(SL)的5A-1171 6A等多态性。根据病史、临床资料和影像研究进行回顾性分析,以评估心脏病的存在情况和类型。我们的研究结果并没有表明这些候选基因的多态性和心脏疾病之间存在密切联系,尤其是与一组西西里岛血红蛋白病患者的心肌梗塞存在密切联系。

  17. Catecholamine and volume therapy for cardiac surgery in Germany--results from a postal survey.

    Directory of Open Access Journals (Sweden)

    Christoph Sponholz

    Full Text Available Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy.Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy.51 (63% questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure, supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%, epinephrine (30% or phosphodiesterase inhibitors (8% were first choice. In case of hypotension following vasoplegia, norepinephrine (96% represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES being first choice (64%.Choice of hemodynamic monitoring is homogenous throughout German centers treating cardiac surgery patients. Norepinephrine is the first line catecholamine in cases of decrease in peripheral vascular resistance. However, catecholamine choice for low cardiac output syndrome varies considerably. HES was the primary colloid used for fluid resuscitation. After conduct of this survey, HES use was restricted by European regulatory authorities in

  18. Iron overload in myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Gattermann, Norbert

    2018-01-01

    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  19. Cardiac size of high-volume resistance trained female athletes: shaping the body but not the heart.

    Science.gov (United States)

    Venckunas, T; Simonavicius, J; Marcinkeviciene, J E

    2016-03-01

    Introduction Exercise training, besides many health benefits, may result in cardiac remodelling which is dependent on the type and amount of exercise performed. It is not clear, however, whether significant adaptation in cardiac structure is possible in females undergoing resistance type of exercise training. Rigorous high volume training of most muscle groups emphasising resistance exercises are being undertaken by athletes of some aesthetic sports such as female fitness (light bodybuilding). The impact of this type of training on cardiac adaptation has not been investigated until now. The aim of the current study was to disclose the effect of high volume resistance training on cardiac structure and function. Methods 11 top-level female fitness athletes and 20 sedentary age-matched controls were recruited to undergo two-dimensional echocardiography. Results Cardiac structure did not differ between elite female fitness athletes and controls (p > 0.05), and fitness athletes had a tendency for a smaller (p = 0.07) left ventricular (LV) mass indexed to lean body mass. Doppler diastolic function index (E/A ratio) and LV ejection fraction were similar between the groups (p > 0.05). Conclusions Elite female fitness athletes have normal cardiac size and function that do not differ from matched sedentary controls. Consequently, as high volume resistance training has no easily observable effect on adaptation of cardiac structure, when cardiac hypertrophy is present in young resistance-trained lean female, other reasons such as inherited cardiac disease are to be considered carefully.

  20. Localization of cardiac volume and patient features in inverse geometry x-ray fluoroscopy

    Science.gov (United States)

    Speidel, Michael A.; Slagowski, Jordan M.; Dunkerley, David A. P.; Wagner, Martin; Funk, Tobias; Raval, Amish N.

    2017-03-01

    The scanning-beam digital x-ray (SBDX) system is an inverse geometry x-ray fluoroscopy technology that performs real-time tomosynthesis at planes perpendicular to the source-detector axis. The live display is a composite image which portrays sharp features (e.g. coronary arteries) extracted from a 16 cm thick reconstruction volume. We present a method for automatically determining the position of the cardiac volume prior to acquisition of a coronary angiogram. In the algorithm, a single non-contrast frame is reconstructed over a 44 cm thickness using shift-and-add digital tomosynthesis. Gradient filtering is applied to each plane to emphasize features such as the cardiomediastinal contour, diaphragm, and lung texture, and then sharpness vs. plane position curves are generated. Three sharpness metrics were investigated: average gradient in the bright field, maximum gradient, and the number of normalized gradients exceeding 0.5. A model correlating the peak sharpness in a non-contrast frame and the midplane of the coronary arteries in a contrast-enhanced frame was established using 37 SBDX angiographic loops (64-136 kg human subjects, 0-30° cranial- caudal). The average gradient in the bright field (primarily lung) and the number of normalized gradients >0.5 each yielded peaks correlated to the coronary midplane. The rms deviation between the predicted and true midplane was 1.57 cm. For a 16 cm reconstruction volume and the 5.5-11.5 cm thick cardiac volumes in this study, midplane estimation errors of 2.25-5.25 cm were tolerable. Tomosynthesis-based localization of cardiac volume is feasible. This technique could be applied prior to coronary angiography, or to assist in isocentering the patient for rotational angiography.

  1. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.

    Science.gov (United States)

    Das, Subhash K; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B; Hajjar, Roger J; Dyck, Jason R B; Kassiri, Zamaneh; Oudit, Gavin Y

    2015-12-07

    Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.

  2. Measurement of four chambers' volumes and ventricular masses by cardiac CT examination

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Motomasa; Naito, Hiroaki; Ohta, Mitsushige; Kozuka, Takahiro; Kito, Yoshitsugu (National Cardiovascular Center, Suita, Osaka (Japan))

    1983-09-01

    Using cardiac computed tomography (CT), the ''mean'' volume of each cardiac chamber and both ventricular masses were calculated from summation of a sliced volume by ungated scans obtained using rapid sequential scanning covering the whole heart. 1. Estimation of a normal value of each chamber's volume was attempted in 20 patients with ischemic heart disease and with normal heart function. The ''mean'' volume of the right atrium (RAMV), right ventricle (RVMV), and left atrium (LAMV) was 22.3 +- 6.5, 40.3 +- 6.5 and 28.7 +- 8.2ml/m/sup 2/, respectively. 2. In 54 patients with valvular heart diseases, each chamber's volume obrained by CT was compared with the grade of tricuspid regurgitation (TR) estimated by ultrasonic Doppler technique or the grade of mitral regurgitation (MR) by left ventriculography (LVG). The RAMV (234 +- 119 ml/m/sup 2/) and the RVMV (101 +- 39 ml/m/sup 2/) were markedly increased in patients with severe TR (grade 3 to 4) (p<0.01). The LAMV (487 +- 231 ml/m/sup 2/) was also increased in patients with severe mitral regurgitation (grade 3 to 4) (p<0.01). 3. In 46 patients with valvular heart diseases, the LVMV by CT was well correlated with end-diastolic volume (EDV) obtained by LVG (r=0.92), and the LVEDVs by ECG gated CT and by LVG showed a fairly good correlation (r=0.95). 4. CT examination was performed before and after surgery in 17 patients with MR or TR for evaluation of the change of chamber volumes. The mean reduction ratio (MRR) of the RAMV after tricuspid annuloplasty, the LVMV after mitral valve plasty, and the LAMV after left atrial plication was 44%, 41%, and 60%, respectively.

  3. Volume of the left ventricle at the end of a ventricular diastole in computerised tomography compared with cardiac catheter ventriculography

    Energy Technology Data Exchange (ETDEWEB)

    Rienmueller, R.; Lissner, J.; Kment, A.; Bohn, J.; Strauer, B.E.; Hellwig, D.; Erdmann, E.; Cyran, J.; Steinbeck, G.

    1981-06-01

    In 47 patients the authors calculated the volume at the end of a diastole according to both the cardiac catheter ventriculogram and the CT ventriculogram, comparing the results obtained with each of these methods. A linear regression was found. The correlation coefficient was approximately r = 0.96; n = 47. Cardiological examination revealed that of the examined patients (including the cardiac catheter finding) 18 patients had coronary heart disease, whereas 9 had cardiomyopathy, 6 artial hypertension, 9 had various cardiac abnormalities and 5 did not show any organically manifest heart disease. The article discusses CT determination of the volume at the end of the ventricular diastole, and discusses the results.

  4. Slice-to-volume parametric image registration models with applications to MRI-guided cardiac procedures

    Science.gov (United States)

    Ma, L. W. Lorraine; Ebrahimi, Mehran

    2017-03-01

    A mathematical formulation for intensity-based slice-to-volume registration is proposed. The approach is flexible and accommodates various regularization schemes, similarity measures, and optimizers. The framework is evaluated by registering 2D and 3D cardiac magnetic resonance (MR) images obtained in vivo, aimed at real- time MR-guided applications. Rigid-body and affine transformations are used to validate the parametric model. Target registration error (TRE), Jaccard, and Dice indices are used to evaluate the algorithm and demonstrate the accuracy of the registration scheme on both simulated and clinical data. Registration with the affine model appeared to be more robust than with the rigid model in controlled cases. By simply extending the rigid model to an affine model, alignment of the cardiac region generally improved, without the need for complex dissimilarity measures or regularizers.

  5. Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

    Directory of Open Access Journals (Sweden)

    Petrak Jiri

    2011-11-01

    Full Text Available Abstract Background Chronic hemodynamic overloading leads to heart failure (HF due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF and sham-operated rats harvested at the advanced, decompensated stage of HF. Methods We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. Results In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. Conclusions The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.

  6. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model

    Directory of Open Access Journals (Sweden)

    Qifeng Zhou

    2015-01-01

    Full Text Available Mutations in the giant sarcomeric protein titin (TTN are a major cause for inherited forms of dilated cardiomyopathy (DCM. We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC in heterozygous (Het Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p<0.05, while wild-type (WT TAC mice did not. Het mice also trended toward increased ventricular end diastolic pressure and volume compared to WT littermates. We found an increase in histologically diffuse cardiac fibrosis in Het compared to WT in TAC mice. This study shows that a pattern of DCM can be induced by TAC-mediated pressure overload in a TTN-truncated mouse model. This model enlarges our arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure.

  7. News and the overloaded consumer: factors influencing information overload among news consumers.

    Science.gov (United States)

    Holton, Avery E; Chyi, Hsiang Iris

    2012-11-01

    News producers continue to increase their volume of production and delivery platforms in an effort to reach and maintain news consumers. However, consumers may not necessarily find more news desirable. Previous studies have suggested that information surplus can lead to negative outcomes for consumers, but research of outcomes related to news production and consumption has been scant. This study explores novel areas of news surplus and overload, empirically examining factors associated with the degree of perceived overload across a broad spectrum of news delivery platforms. The findings reveal that the majority of today's news consumers feel overloaded with the amount of news they are confronted with. Gender, news interest, and the use of specific news platforms and outlets predict the degree of that overload. News access through platforms and outlets such as computers, e-readers, and Facebook is positively associated with overload, whereas other platforms such as television and the iPhone are negatively associated with overload. Implications for media psychology and news consumption are discussed.

  8. Goal-directed fluid therapy: stroke volume optimisation and cardiac dimensions in supine healthy humans

    DEFF Research Database (Denmark)

    Jans, O.; Tollund, C.; Bundgaard-Nielsen, M.

    2008-01-01

    by thoracic electrical admittance, central venous oxygenation and pressure, and arterial plasma atrial natriuretic peptide. Also, muscle and brain oxygenation were assessed by near infrared spectroscopy (n=7). RESULTS: The HUT reduced the mentioned indices of CBV, the end-diastolic dimensions of the heart......BACKGROUND: Based on maximisation of cardiac stroke volume (SV), peri-operative individualised goal-directed fluid therapy improves patient outcome. It remains, however, unknown how fluid therapy by this strategy relates to filling of the heart during supine rest as reference for the anaesthetised......, and SV. Conversely, HDT-enhanced tissue oxygenation and the diastolic filling of the heart, but not SV. CONCLUSIONS: In healthy supine humans, the heart is provided with a volume that is sufficient to secure a maximal SV without distending the heart. The implication for individualised goal-directed fluid...

  9. Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity

    Science.gov (United States)

    Prisk, G. K.; Guy, Harold J. B.; Elliott, Ann R.; Deutschman, Robert A., III; West, John B.

    1993-01-01

    We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to nine days of microgravity. DL in microgravity was elevated compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc and Dm. The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value. We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to eight days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased inflight and decreased postflight compared with preflight standing. Compared with preflight standing, SV was increased 46 percent inflight and decreased 14 percent in the 1st week postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

  10. 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

  11. A Diet Rich in Unsaturated Fatty Acids Prevents Progression Toward Heart Failure in a Rabbit Model of Pressure and Volume Overload

    NARCIS (Netherlands)

    den Ruijter, Hester M.; Verkerk, Arie O.; Schumacher, Cees A.; Houten, Sander M.; Belterman, Charly N. W.; Baartscheer, Antonius; Brouwer, Ingeborg A.; van Bilsen, Marc; de Roos, Baukje; Coronel, Ruben

    2012-01-01

    Background-During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary omega 3-FAs have an added

  12. A novel cardiac MR chamber volume model for mechanical dyssynchrony assessment

    Science.gov (United States)

    Song, Ting; Fung, Maggie; Stainsby, Jeffrey A.; Hood, Maureen N.; Ho, Vincent B.

    2009-02-01

    A novel cardiac chamber volume model is proposed for the assessment of left ventricular mechanical dyssynchrony. The tool is potentially useful for assessment of regional cardiac function and identification of mechanical dyssynchrony on MRI. Dyssynchrony results typically from a contraction delay between one or more individual left ventricular segments, which in turn leads to inefficient ventricular function and ultimately heart failure. Cardiac resynchronization therapy has emerged as an electrical treatment of choice for heart failure patients with dyssynchrony. Prior MRI techniques have relied on assessments of actual cardiac wall changes either using standard cine MR images or specialized pulse sequences. In this abstract, we detail a semi-automated method that evaluates dyssynchrony based on segmental volumetric analysis of the left ventricular (LV) chamber as illustrated on standard cine MR images. Twelve sectors each were chosen for the basal and mid-ventricular slices and 8 sectors were chosen for apical slices for a total of 32 sectors. For each slice (i.e. basal, mid and apical), a systolic dyssynchrony index (SDI) was measured. SDI, a parameter used for 3D echocardiographic analysis of dyssynchrony, was defined as the corrected standard deviation of the time at which minimal volume is reached in each sector. The SDI measurement of a healthy volunteer was 3.54%. In a patient with acute myocardial infarction, the SDI measurements 10.98%, 16.57% and 1.41% for basal, mid-ventricular and apical LV slices, respectively. Based on published 3D echocardiogram reference threshold values, the patient's SDI corresponds to moderate basal dysfunction, severe mid-ventricular dysfunction, and normal apical LV function, which were confirmed on echocardiography. The LV chamber segmental volume analysis model and SDI is feasible using standard cine MR data and may provide more reliable assessment of patients with dyssynchrony especially if the LV myocardium is thin or if

  13. Interdisciplinary Research and Information Overload.

    Science.gov (United States)

    Wilson, Patrick

    1996-01-01

    Discusses information overload and examines several ways in which actual and potential overload affects research choices for the solo researcher in interdisciplinary areas. Topics include information overload and teamwork; entry barriers to certain specialties, including necessary background knowledge; and information utilization and knowledge…

  14. Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload.

    Science.gov (United States)

    Gao, Xueshan; Qian, Mingwei; Campian, Jian Li; Marshall, James; Zhou, Zhanxiang; Roberts, Andrew M; Kang, Y James; Prabhu, Sumanth D; Sun, Xiao-Feng; Eaton, John W

    2010-08-01

    In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. qPCR amplification of near-full-length ( approximately 16kb) mtDNA revealed >50% loss of full-length product, whereas amounts of a qPCR product of a nuclear gene (13kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60-70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  15. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Sestili, Paola; Massimi, Alessia; Corritore, Elisa; Marano, Giuseppe; Catalano, Liviana

    2013-01-01

    Background Chronic transfusion therapy causes a progressive iron overload that damages many organs including the heart. Recent evidence suggests that L-type calcium channels play an important role in iron uptake by cardiomyocytes under conditions of iron overload. Given that beta-adrenergic stimulation significantly enhances L-type calcium current, we hypothesised that beta-adrenergic blocking drugs could reduce the deleterious effects of iron overload on the heart. Methods Iron overload was generated by intraperitoneal injections of iron dextran (1g/kg) administered once a week for 8 weeks in male C57bl/6 mice, while propranolol was administered in drinking water at the dose of 40 mg/kg/day. Cardiac function and ventricular remodelling were evaluated by echocardiography and histological methods. Results As compared to placebo, iron injection caused cardiac iron deposition. Surprisingly, despite iron overload, myocardial function and ventricular geometry in the iron-treated mice resulted unchanged as compared to those in the placebo-treated mice. Administration of propranolol increased cardiac performance in iron-overloaded mice. Specifically, as compared to the values in the iron-overloaded group, in iron-overloaded animals treated with propranolol left ventricular fractional shortening increased (from 31.6% to 44.2%, P =0.01) whereas left ventricular end-diastolic diameter decreased (from 4.1±0.1 mm to 3.5±0.1 mm, P =0.03). Propranolol did not alter cardiac systolic function or left ventricular sizes in the placebo group. Conclusions These results demonstrate that C57bl/6 mice are resistant to iron overload-induced myocardial injury and that treatment with propranolol is able to increase cardiac performance in iron-overloaded mice. However, since C57bl/6 mice were resistant to iron-induced injury, it remains to be evaluated further whether propranolol could prevent iron-overload cardiomyopathy. PMID:22790263

  16. Pulse dye densitometry using indigo carmine is useful for cardiac output measurement, but not for circulating blood volume measurement.

    Science.gov (United States)

    Fujita, Y; Yamamoto, T; Fuse, M; Kobayashi, N; Takeda, S; Aoyagi, T

    2004-08-01

    We evaluated the validity of a newly developed pulse dye densitometer for indigo carmine for measuring cardiac output and circulating blood volume. Measurements of cardiac output and circulating blood volume were performed with the indigo carmine densitometer during normovolaemia, hypovolaemia and hypervolaemia in nine mongrel dogs under general anaesthesia. The validity was evaluated by comparison of the values of cardiac output and circulating blood volume obtained by the thermodilution technique and the 51Cr-labelled red blood cell method, respectively. We also examined indigo carmine removal by continuous veno-venous haemofiltration after indigo carmine injection. There was good agreement between dye densitometer- and thermodilution-derived cardiac output (r = 0.885, P indigo carmine through continuous veno-venous haemofiltration was 0.34+/-0.06. These data indicate that indigo carmine densitometry is a reliable method for cardiac output determination, but it overestimates circulating blood volume, probably due to the transition of indigo carmine into the extravascular space in the systemic circulation.

  17. Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery.

    Science.gov (United States)

    Schramko, Alexey A; Suojaranta-Ylinen, Raili T; Kuitunen, Anne H; Raivio, Peter M; Kukkonen, Sinikka I; Niemi, Tomi T

    2010-09-01

    The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery. Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1). Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group.

  18. Novel cardiac magnetic resonance biomarkers: native T1 and extracellular volume myocardial mapping

    Science.gov (United States)

    Cannaò, Paola Maria; Altabella, Luisa; Petrini, Marcello; Alì, Marco; Secchi, Francesco; Sardanelli, Francesco

    2016-01-01

    Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping. PMID:28533719

  19. Rowing increases stroke volume and cardiac output to a greater extent than cycling.

    Science.gov (United States)

    Horn, P; Ostadal, P; Ostadal, B

    2015-01-01

    Exercise stimulates increases in heart rate (HR), stroke volume (SV) and cardiac output (CO). These adaptive mechanisms are strongly dependent on the type of exercise. Both rowing and cycling are widely used for physical training worldwide; however, evidence regarding the differences in major hemodynamic parameters during rowing and cycling remains insufficient. Ten healthy male volunteers were randomly assigned to perform either a rowing or cycling exercise. After 20 min rest, the group who had rowed first performed the cycling exercise and vice versa. Exercise was performed at a power-to-weight ratio of 2 W/kg for 2 min. HR, SV, CO and blood pressure (BP) were measured noninvasively using pulse-wave analysis at baseline and immediately after each exercise. HR, SV and CO were significantly higher after exercise than at rest. Whereas HR was comparable between rowing and cycling, SV and CO were significantly higher after rowing than after cycling. BP was comparable among all three measurements. Rowing increased SV and CO to a greater extent than cycling, whereas HR and BP were not influenced by the type of exercise. Our data suggest that rowing leads to more extensive stimulation of cardiac contractility and/or decreases in peripheral vascular resistance compared with cycling.

  20. A framework of whole heart extracellular volume fraction estimation for low dose cardiac CT images

    Science.gov (United States)

    Chen, Xinjian; Summers, Ronald M.; Nacif, Marcelo Souto; Liu, Songtao; Bluemke, David A.; Yao, Jianhua

    2012-02-01

    Cardiac magnetic resonance imaging (CMRI) has been well validated and allows quantification of myocardial fibrosis in comparison to overall mass of the myocardium. Unfortunately, CMRI is relatively expensive and is contraindicated in patients with intracardiac devices. Cardiac CT (CCT) is widely available and has been validated for detection of scar and myocardial stress/rest perfusion. In this paper, we sought to evaluate the potential of low dose CCT for the measurement of myocardial whole heart extracellular volume (ECV) fraction. A novel framework was proposed for CCT whole heart ECV estimation, which consists of three main steps. First, a shape constrained graph cut (GC) method was proposed for myocardium and blood pool segmentation for post-contrast image. Second, the symmetric Demons deformable registrations method was applied to register pre-contrast to post-contrast images. Finally, the whole heart ECV value was computed. The proposed method was tested on 7 clinical low dose CCT datasets with pre-contrast and post-contrast images. The preliminary results demonstrated the feasibility and efficiency of the proposed method.

  1. Reference values for total blood volume and cardiac output in humans

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L.R. [Indiana Univ., South Bend, IN (United States). Division of Liberal Arts and Sciences

    1994-09-01

    Much research has been devoted to measurement of total blood volume (TBV) and cardiac output (CO) in humans but not enough effort has been devoted to collection and reduction of results for the purpose of deriving typical or {open_quotes}reference{close_quotes} values. Identification of normal values for TBV and CO is needed not only for clinical evaluations but also for the development of biokinetic models for ultra-short-lived radionuclides used in nuclear medicine (Leggett and Williams 1989). The purpose of this report is to offer reference values for TBV and CO, along with estimates of the associated uncertainties that arise from intra- and inter-subject variation, errors in measurement techniques, and other sources. Reference values are derived for basal supine CO and TBV in reference adult humans, and differences associated with age, sex, body size, body position, exercise, and other circumstances are discussed.

  2. Temperature-based on-column solute focusing in capillary liquid chromatography reduces peak broadening from pre-column dispersion and volume overload when used alone or with solvent-based focusing.

    Science.gov (United States)

    Groskreutz, Stephen R; Horner, Anthony R; Weber, Stephen G

    2015-07-31

    On-column focusing is essential for satisfactory performance using capillary scale columns. On-column focusing results from generating transient conditions at the head of the column that lead to high solute retention. Solvent-based on-column focusing is a well-known approach to achieve this. Temperature-assisted on-column focusing (TASF) can also be effective. TASF improves focusing by cooling a short segment of the column inlet to a temperature that is lower than the column temperature during the injection and then rapidly heating the focusing segment to the match the column temperature. A troublesome feature of an earlier implementation of TASF was the need to leave the capillary column unpacked in that portion of the column inside the fitting connecting it to the injection valve. We have overcome that problem in this work by packing the head of the column with solid silica spheres. In addition, technical improvements to the TASF instrumentation include: selection of a more powerful thermo-electric cooler to create faster temperature changes and electronic control for easy incorporation into conventional capillary instruments. Used in conjunction with solvent-based focusing and with isocratic elution, volumes of paraben samples (esters of p-hydroxybenzoic acid) up to 4.5-times the column liquid volume can be injected without significant bandspreading due to volume overload. Interestingly, the shapes of the peaks from the lowest volume injections that we can make, 30nL, are improved when using TASF. TASF is very effective at reducing the detrimental effects of pre-column dispersion using isocratic elution. Finally, we show that TASF can be used to focus the neuropeptide galanin in a sample solvent with elution strength stronger than the mobile phase. Here, the stronger solvent is necessitated by the need to prevent peptide adsorption prior to and during analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Effect of tidal volume, sampling duration, and cardiac contractility on pulse pressure and stroke volume variation during positive-pressure ventilation.

    Science.gov (United States)

    Kim, Hyung Kook; Pinsky, Michael R

    2008-10-01

    Both pulse pressure variation and stroke volume variation during intermittent positive-pressure ventilation predict preload responsiveness. However, because ventilatory and cardiac frequencies are not the same, increasing the number of breaths sampled may increase calculated pulse pressure variation and stroke volume variation because larger (max) and smaller (min) pulse pressure and stroke volume may occur. Tidal volume and contractility may also alter pulse pressure variation and stroke volume variation. We hypothesized that the magnitude of pulse pressure variation would increase with sampling duration, and that both tidal volume and contractility would independently alter pulse pressure variation and stroke volume variation. In seven pentobarbital-anesthetized intact dogs arterial and left ventricular pressure (Millar) and left ventricular volume (Leycom) were measured over 8 intermittent positive-pressure ventilation breaths at tidal volume of 5, 10, 15, and 20 mL/kg (f = 20/min, 40% inspiratory time) under baseline, esmolol (2 mg/min), dobutamine infusions (5 microg/kg/min) and following volume loading (500 mL NaCl). Stroke volume variation was calculated using pulse contour method (PiCCO, Pulsion Medical Systems, Munich, Germany) averaged over 12 secs. Pulse pressure variation was calculated as 100 x (PPmax - PPmin)/PPmean and calculated over 1, 2, 3, 4, 5, 6, 7, or 8 breaths. Pulse pressure variation increased progressively with increasing sampling duration up to but not exceeding five breaths. The effect on sampling duration was increased by greater tidal volume. Esmolol infusion decreased both pulse pressure variation and stroke volume variation as compared with baseline (p variation or stroke volume variation. Sampling duration, tidal volume, and beta-adrenergic blockade differentially alters pulse pressure variation and stroke volume variation during intermittent positive-pressure ventilation. Thus, separate validation is required to define threshold

  4. Personalization of a cardiac electromechanical model using reduced order unscented Kalman filtering from regional volumes.

    Science.gov (United States)

    Marchesseau, S; Delingette, H; Sermesant, M; Cabrera-Lozoya, R; Tobon-Gomez, C; Moireau, P; Figueras i Ventura, R M; Lekadir, K; Hernandez, A; Garreau, M; Donal, E; Leclercq, C; Duckett, S G; Rhode, K; Rinaldi, C A; Frangi, A F; Razavi, R; Chapelle, D; Ayache, N

    2013-10-01

    Patient-specific cardiac modeling can help in understanding pathophysiology and therapy planning. However it requires to combine functional and anatomical data in order to build accurate models and to personalize the model geometry, kinematics, electrophysiology and mechanics. Personalizing the electromechanical coupling from medical images is a challenging task. We use the Bestel-Clément-Sorine (BCS) electromechanical model of the heart, which provides reasonable accuracy with a reasonable number of parameters (14 for each ventricle) compared to the available clinical data at the organ level. We propose a personalization strategy from cine MRI data in two steps. We first estimate global parameters with an automatic calibration algorithm based on the Unscented Transform which allows to initialize the parameters while matching the volume and pressure curves. In a second step we locally personalize the contractilities of all AHA (American Heart Association) zones of the left ventricle using the reduced order unscented Kalman filtering on Regional Volumes. This personalization strategy was validated synthetically and tested successfully on eight healthy and three pathological cases. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Simulation of elution profiles in liquid chromatography - II: Investigation of injection volume overload under gradient elution conditions applied to second dimension separations in two-dimensional liquid chromatography.

    Science.gov (United States)

    Stoll, Dwight R; Sajulga, Ray W; Voigt, Bryan N; Larson, Eli J; Jeong, Lena N; Rutan, Sarah C

    2017-11-10

    An important research direction in the continued development of two-dimensional liquid chromatography (2D-LC) is to improve the detection sensitivity of the method. This is especially important in applications where injection of large volumes of effluent from the first dimension ( 1 D) column into the second dimension ( 2 D) column leads to severe 2 D peak broadening and peak shape distortion. For example, this is common when coupling two reversed-phase columns and the organic solvent content of the 1 D mobile phase overwhelms the 2 D column with each injection of 1 D effluent, leading to low resolution in the second dimension. In a previous study we validated a simulation approach based on the Craig distribution model and adapted from the work of Czok and Guiochon [1] that enabled accurate simulation of simple isocratic and gradient separations with very small injection volumes, and isocratic separations with mismatched injection and mobile phase solvents [2]. In the present study we have extended this simulation approach to simulate separations relevant to 2D-LC. Specifically, we have focused on simulating 2 D separations where gradient elution conditions are used, there is mismatch between the sample solvent and the starting point in the gradient elution program, injection volumes approach or even exceed the dead volume of the 2 D column, and the extent of sample loop filling is varied. To validate this simulation we have compared results from simulations and experiments for 101 different conditions, including variation in injection volume (0.4-80μL), loop filling level (25-100%), and degree of mismatch between sample organic solvent and the starting point in the gradient elution program (-20 to +20% ACN). We find that that the simulation is accurate enough (median errors in retention time and peak width of -1.0 and -4.9%, without corrections for extra-column dispersion) to be useful in guiding optimization of 2D-LC separations. However, this requires that real

  6. Machine learning in the prediction of cardiac epicardial and mediastinal fat volumes.

    Science.gov (United States)

    Rodrigues, É O; Pinheiro, V H A; Liatsis, P; Conci, A

    2017-10-01

    We propose a methodology to predict the cardiac epicardial and mediastinal fat volumes in computed tomography images using regression algorithms. The obtained results indicate that it is feasible to predict these fats with a high degree of correlation, thus alleviating the requirement for manual or automatic segmentation of both fat volumes. Instead, segmenting just one of them suffices, while the volume of the other may be predicted fairly precisely. The correlation coefficient obtained by the Rotation Forest algorithm using MLP Regressor for predicting the mediastinal fat based on the epicardial fat was 0.9876, with a relative absolute error of 14.4% and a root relative squared error of 15.7%. The best correlation coefficient obtained in the prediction of the epicardial fat based on the mediastinal was 0.9683 with a relative absolute error of 19.6% and a relative squared error of 24.9%. Moreover, we analysed the feasibility of using linear regressors, which provide an intuitive interpretation of the underlying approximations. In this case, the obtained correlation coefficient was 0.9534 for predicting the mediastinal fat based on the epicardial, with a relative absolute error of 31.6% and a root relative squared error of 30.1%. On the prediction of the epicardial fat based on the mediastinal fat, the correlation coefficient was 0.8531, with a relative absolute error of 50.43% and a root relative squared error of 52.06%. In summary, it is possible to speed up general medical analyses and some segmentation and quantification methods that are currently employed in the state-of-the-art by using this prediction approach, which consequently reduces costs and therefore enables preventive treatments that may lead to a reduction of health problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Mitochondrial DNA damage in iron overload.

    Science.gov (United States)

    Gao, Xueshan; Campian, Jian Li; Qian, Mingwei; Sun, Xiao-Feng; Eaton, John W

    2009-02-20

    Chronic iron overload has slow and insidious effects on heart, liver, and other organs. Because iron-driven oxidation of most biologic materials (such as lipids and proteins) is readily repaired, this slow progression of organ damage implies some kind of biological "memory." We hypothesized that cumulative iron-catalyzed oxidant damage to mtDNA might occur in iron overload, perhaps explaining the often lethal cardiac dysfunction. Real time PCR was used to examine the "intactness" of mttDNA in cultured H9c2 rat cardiac myocytes. After 3-5 days exposure to high iron, these cells exhibited damage to mtDNA reflected by diminished amounts of near full-length 15.9-kb PCR product with no change in the amounts of a 16.1-kb product from a nuclear gene. With the loss of intact mtDNA, cellular respiration declined and mRNAs for three electron transport chain subunits and 16 S rRNA encoded by mtDNA decreased, whereas no decrements were found in four subunits encoded by nuclear DNA. To examine the importance of the interactions of iron with metabolically generated reactive oxygen species, we compared the toxic effects of iron in wild-type and rho(o) cells. In wild-type cells, elevated iron caused increased production of reactive oxygen species, cytostasis, and cell death, whereas the rho(o) cells were unaffected. We conclude that long-term damage to cells and organs in iron-overload disorders involves interactions between iron and mitochondrial reactive oxygen species resulting in cumulative damage to mtDNA, impaired synthesis of respiratory chain subunits, and respiratory dysfunction.

  8. Capnodynamic assessment of effective lung volume during cardiac output manipulations in a porcine model.

    Science.gov (United States)

    Hällsjö Sander, Caroline; Lönnqvist, Per-Arne; Hallbäck, Magnus; Sipmann, Fernando Suarez; Wallin, Mats; Oldner, Anders; Björne, Håkan

    2016-12-01

    A capnodynamic calculation of effective pulmonary blood flow includes a lung volume factor (ELV) that has to be estimated to solve the mathematical equation. In previous studies ELV correlated to reference methods for functional residual capacity (FRC). The aim was to evaluate the stability of ELV during significant manipulations of cardiac output (CO) and assess the agreement for absolute values and trending capacity during PEEP changes at different lung conditions. Ten pigs were included. Alterations of alveolar carbon dioxide were induced by cyclic reoccurring inspiratory holds. The Sulphur hexafluoride technique for FRC measurements was used as reference. Cardiac output was altered by preload reduction and inotropic stimulation at PEEP 5 and 12 cmH2O both in normal lung conditions and after repeated lung lavages. ELV at baseline PEEP 5 was [mean (SD)], 810 (163) mL and decreased to 400 (42) mL after lavage. ELV was not significantly affected by CO alterations within the same PEEP level. In relation to FRC the overall bias (limits of agreement) was -35 (-271 to 201) mL, and percentage error 36 %. A small difference between ELV and FRC was seen at PEEP 5 cmH2O before lavage and at PEEP 12 cmH2O after lavage. ELV trending capability between PEEP steps, showed a concordance rate of 100 %. ELV was closely related to FRC and remained stable during significant changes in CO. The trending capability was excellent both before and after surfactant depletion.

  9. Correlation between left ventricular diastolic function before and after valve replacement surgery and myocardial ultrastructural changes in patients with left ventricular volume-overloaded valvular heart diseases; Evaluation with gated blood pool scintigraphy using [sup 99m]Tc

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Tomiro (Okayama Univ. (Japan). School of Medicine)

    1993-06-01

    Left ventricular (LV) diastolic functions in 23 patients with aortic regurgitation (AR) and 22 patients with mitral regurgitation (MR) were evaluated by gated blood pool scintigraphy. LV myocardial biopsy was performed during open heart surgery, and LV myocardial ultrastructural changes were evaluated by electron microscope. Correlation between LV diastolic function and myocardial ultrastructural changes was examined. It was suggested that preoperative LV diastolic dysfunction occurred earlier than LV systolic dysfunction in patients with AR and MR. LV early diastolic dysfunction was especially significant in patients with AR. LV systolic function was significantly improved postoperatively compared with LV diastolic function in patients with AR and MR. It was suggested that LV interstitial fibrosis caused LV diastolic dysfunction in patients with AR and MR, and insufficiency of myocardial thickening as compensation in patients with MR. It was presumed that LV diastolic dysfunction was irreversible in patients with AR and MR in the distant postoperative period due to persistence of the preoperative myocardial ultrastructural change, e.g., interstitial fibrosis. These LV diastolic indices measured by gated pool scintigraphy were useful in predicting LV ultrastructural changes and postoperative LV dysfunction in patients with LV volume-overloaded valvular heart disease. (author).

  10. Right and left ventricular function and myocardial scarring in adult patients with sickle cell disease: a comprehensive magnetic resonance assessment of hepatic and myocardial iron overload.

    Science.gov (United States)

    Junqueira, Flávia P; Fernandes, Juliano L; Cunha, Guilherme M; T A Kubo, Tadeu; M A O Lima, Claudio; B P Lima, Daniel; Uellendhal, Marly; Sales, Sidney R; A S Cunha, Carolina; L R de Pessoa, Viviani; L C Lobo, Clarisse; Marchiori, Edson

    2013-09-19

    Patients with Sickle cell disease (SCD) who receive regular transfusions are at risk for developing cardiac toxicity from iron overload. The aim of this study was to assess right and left cardiac volumes and function, late gadolinium enhancement (LGE) and iron deposits in patients with SCD using CMR, correlating these values with transfusion burden, ferritin and hemoglobin levels. Thirty patients with SCD older than 20 years of age were studied in a 1.5 T scanner and compared to age- and sex-matched normal controls. Patients underwent analysis of biventricular volumes and function, LGE and T2* assessment of the liver and heart. When compared to controls, patients with SCD presented higher left ventricular (LV) volumes with decreased ejection fraction (EF) with an increase in stroke volume (SV) and LV hypertrophy. The right ventricle (RV) also presented with a decreased EF and hypertrophy, with an increased end-systolic volume. Although twenty-six patients had increased liver iron concentrations (median liver iron concentration value was 11.83 ± 9.66 mg/g), only one patient demonstrated an abnormal heart T2* < 20 msec. Only four patients (13%) LGE, with only one patient with an ischemic pattern. Abnormal heart iron levels and myocardial scars are not a common finding in SCD despite increased liver iron overload. The significantly different ventricular function seen in SCD compared to normal suggests the changes in RV and LV function may not be due to the anemia alone. Future studies are necessary to confirm this association.

  11. Effect of iterative reconstruction on variability and reproducibility of epicardial fat volume quantification by cardiac CT.

    Science.gov (United States)

    Oda, Seitaro; Utsunomiya, Daisuke; Funama, Yoshinori; Yuki, Hideaki; Kidoh, Masafumi; Nakaura, Takeshi; Takaoka, Hiroko; Matsumura, Masaki; Katahira, Kazuhiro; Noda, Katsuo; Oshima, Shuichi; Tokuyasu, Shinichi; Yamashita, Yasuyuki

    2016-01-01

    The epicardial fat volume (EFV) measured by cardiac CT has emerged as an important parameter for understanding the pathophysiology of coronary atherosclerosis. We investigated the variability and reproducibility of EFV measurements and evaluated the effect of model-based type iterative reconstruction (M-IR) on measurement results. Non-contrast cardiac CT data (tube voltage 120-kVp, tube current time product 32 mAs) of 30 consecutive patients were reconstructed with filtered back projection (FBP), hybrid type iterative reconstruction (H-IR), and M-IR using a slice thickness of 3.0 mm. CT attenuation and image noise was measured for all reconstructions. Two observers independently quantified EFV using semi-automated software and interobserver agreement was evaluated. There was no significant difference in the CT attenuation of the ascending aorta among the three reconstructions. The mean image noise on FBP-, H-IR-, and M-IR images was 48.0 ± 7.9 HU, 29.6 ± 4.8 HU, and 9.3 ± 1.3 HU, respectively; there was a significant difference among all comparison combinations for the three reconstructions (p reconstructions (171.0 ± 54.9 cm(3) [FBP], 153.8 ± 53.1 cm(3) [H-IR], and 134.0 ± 46.4 cm(3) [M-IR]). For all three reconstructions, interobserver correlations were excellent (r = 0.91 [FBP], 0.93 [H-IR], and 0.96 [M-IR]). Interobserver comparisons showed that the lowest Bland-Altman limit of agreement was with M-IR (mean difference 2.0 ± 4.9%, 95% limit of agreement, -24.0 to 28.0%) followed by H-IR (-2.6 ± 7.1%, -39.8 to 34.6%) and FBP (-0.2 ± 8.6%, -45.3- to 45.0%). For the quantification of epicardial fat by cardiac CT, model-based iterative reconstruction can improve the image quality and lessen measurement variability. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  12. The Mythology of Information Overload.

    Science.gov (United States)

    Tidline, Tonyia J.

    1999-01-01

    Combines ideas from mythology, folklore, and library and information science to conclude that information overload is a myth of modern culture. Reports results of a pilot project intended to describe information overload experienced by a particular folk group composed of future library and information professionals. (Author/LRW)

  13. 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.

  14. Automatic quantification of the myocardial extracellular volume by cardiac computed tomography: Synthetic ECV by CCT.

    Science.gov (United States)

    Treibel, Thomas A; Fontana, Marianna; Steeden, Jennifer A; Nasis, Arthur; Yeung, Jason; White, Steven K; Sivarajan, Sri; Punwani, Shonit; Pugliese, Francesca; Taylor, Stuart A; Moon, James C; Bandula, Steve

    The quantification of extracellular volume fraction (ECV) by Cardiac Computed Tomography (CCT) can identify changes in the myocardial interstitium due to fibrosis or infiltration. Current methodologies require laboratory blood hematocrit (Hct) measurement - which complicates the technique. The attenuation of blood (HUblood) is known to change with anemia. We hypothesized that the relationship between Hct and HUblood could be calibrated to rapidly generate a synthetic ECV without formally measuring Hct. The association between Hct and HUblood was derived from forty non-contrast thoracic CT scans using regression analysis. Synthetic Hct was then used to calculate synthetic ECV, and in turn compared with ECV using blood Hct in a validation cohort with mild interstitial expansion due to fibrosis (aortic stenosis, n = 28, ECVCT = 28 ± 4%) and severe interstitial expansion due to amyloidosis (n = 27; ECVCT = 54 ± 11%, p ECV was correlated with collagen volume fraction (CVF) in a separate cohort with aortic stenosis (n = 18). All CT scans were performed at 120 kV and 160 mAs. HUblood was a good predictor of Hct (R(2) = 0.47; p ECV correlated well with conventional ECV (R(2) = 0.96; p ECV correlated as well as conventional ECV with histological CVF (both R(2) = 0.50, p ECV plug-in for offline analysis. Synthetic ECV by CCT provides instantaneous quantification of the myocardial extracellular space without the need for blood sampling. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  15. How will you need me, how will you read me, when I'm 64 (or more!)?: volume computed tomographic scanning and information overload in the emergency department.

    Science.gov (United States)

    Chason, David P; Anderson, Jon A; Stephens, Jason S; Suss, Richard A; Guild, Jeffrey B; Blackburn, Timothy J; Champine, Julie G; Lane, Thomas J

    2010-01-01

    Computed tomographic (CT) scanning technology now employs up to 320 detector rows of 0.5-mm width and allows rapid acquisition of isotropic volume datasets over the entire body. Data from a single CT acquisition can be reconstructed into image series that would formerly have required multiple acquisitions. Small isotropic voxels permit scan parameters to be general while reconstruction algorithms remain specific to anatomy. While this results in more efficient operation in the Emergency Department, it necessitates new ways of displaying, interpreting, and archiving the information. Critical decisions include how much of the patient to scan and how to time contrast injections when imaging multiple organs. These choices must be made in light of dose considerations to the patient and the general population of patients. The technical basis of high-density CT scanning is discussed, including detector configurations and reconstruction techniques. Volumetric scanning in the Emergency Department can improve patient care but requires a change of technical habits. 2010 Mosby, Inc. All rights reserved.

  16. Normovolemia defined according to cardiac stroke volume in healthy supine humans

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, Morten; Jørgensen, Christoffer C; Kehlet, Henrik

    2010-01-01

    was obtained. RESULTS: None of the subjects increased SV >or=10% following fluid administration but there was a minor increase in mean arterial pressure (92 +/- 15 to 93 +/- 12 mmHg, P = 0.01), while heart rate (HR) (66 +/- 12 beats min(-1); P = 0.32), cardiac output (4.8 +/- 1.1 l min(-1); P = 0.......25) and the length of the systole corrected to a HR of 60 beats/min (corrected flow time; 344 +/- 24 ms; P = 0.31) did not change. CONCLUSION: Supporting the proposed definition of normovolemia, non-fasting, supine, healthy subjects are provided with a preload to the heart that does not limit SV suggesting...... of the Frank-Starling curve is reached when subjects are supine and that finding may be applicable for a clinical definition of normovolemia. However, it is unknown whether stroke volume (SV) responds to an increase in preload induced by fluid administration. METHODS: In 20 healthy subjects (23 +/- 2 years...

  17. ANP and BNP in atrial fibrillation before and after cardioversion--and their relationship to cardiac volume and function.

    Science.gov (United States)

    Therkelsen, Susette Krohn; Groenning, Bjoern Aaris; Kjaer, Andreas; Svendsen, Jesper Hastrup; Boje Jensen, Gorm

    2008-07-21

    The role of atrial (ANP) and B-type (BNP) natriuretic peptide in atrial fibrillation (AF) is not clear. Our aim was to describe ANP and BNP in AF, and their changes following cardioversion in persistent AF. Furthermore, we wanted to assess the association between ANP and BNP and cardiac volume and function evaluated by magnetic resonance imaging. ANP and BNP decreased significantly following cardioversion. After 180 days of sinus rhythm, ANP and BNP were still significantly elevated. Same results were seen in patients with lone AF. Left and right atrial volumes correlated positively with ANP and BNP. Changes in left atrial volume were predictive of changes in ANP and BNP following cardioversion. AF may cause enduringly elevated ANP and BNP and atrial volume seems to be an important determinant of ANP and BNP in AF.

  18. ANP and BNP in atrial fibrillation before and after cardioversion--and their relationship to cardiac volume and function

    DEFF Research Database (Denmark)

    Therkelsen, Susette Krohn; Groenning, Bjoern Aaris; Kjaer, Andreas

    2007-01-01

    The role of atrial (ANP) and B-type (BNP) natriuretic peptide in atrial fibrillation (AF) is not clear. Our aim was to describe ANP and BNP in AF, and their changes following cardioversion in persistent AF. Furthermore, we wanted to assess the association between ANP and BNP and cardiac volume...... and function evaluated by magnetic resonance imaging. ANP and BNP decreased significantly following cardioversion. After 180 days of sinus rhythm, ANP and BNP were still significantly elevated. Same results were seen in patients with lone AF. Left and right atrial volumes correlated positively with ANP and BNP....... Changes in left atrial volume were predictive of changes in ANP and BNP following cardioversion. AF may cause enduringly elevated ANP and BNP and atrial volume seems to be an important determinant of ANP and BNP in AF....

  19. Overload road damage model

    CSIR Research Space (South Africa)

    Roux, MP

    2005-03-01

    Full Text Available .02 1.07 1.02 1.07 1.05 Current Condition: Provincial 1.07 1.17 1.03 1.08 1.05 1.12 1.05 1.12 1.09 Deteriorated Condition 1.14 1.27 1.06 1.14 1.10 1.18 1.10 1.20 1.15 TR 2005/26 - TBP51: Overload Road Damage Model Report – March 2005 CSIR... million Ave. O/L E80s/vehicle (n=4) Low High Average 1996 50,595 14,220 16% 1.28 19.7 40.4 30.1 1997 45,657 13,691 15% 1.31 18.8 38.9 28.9 1998 33,235 14,291 15% 1.22 17.6 36.2 26.9 1999 72,546 25,788 15% 1.13 16.3 33.4 24.9 2000 135...

  20. Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Tani Tomoko

    2011-11-01

    Full Text Available Abstract Aims To prospectively evaluate the relationship between left atrial volume (LAV and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM. Methods We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE, a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. Results MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths. Maximum LAV, minimum LAV, and LAV index (LAVI corrected for body surface area (BSA were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm2, p = 0.0009, while there were no differences in the other echocardiographic parameters. LAV/BSA of ≥ 40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. Conclusion LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

  1. Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload

    NARCIS (Netherlands)

    Koitabashi, Norimichi; Danner, Thomas; Zaiman, Ari L.; Pinto, Yigal M.; Rowell, Janelle; Mankowski, Joseph; Zhang, Dou; Nakamura, Taishi; Takimoto, Eiki; Kass, David A.

    2011-01-01

    The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted

  2. Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Amir Abbas Mahabadi

    Full Text Available Epicardial adipose tissue (EAT volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction.In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28 had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07 and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03 than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02. EAT volume increased per standard deviation of age (18.2 [6.2-30.2] ml, p = 0.003, BMI (29.3 [18.4-40.2] ml, p<0.0001, and with presence of diabetes (44.5 [16.7-72.3] ml, p = 0.0002, while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08-4.61] HU, p = 0.04. In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10-2.94], p = 0.02 for volume, 2.04 [1.18-3.53], p = 0.01 for attenuation. Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77-2.68], p = 0.26 for volume; 1.93 [1.11-3.39], p = 0.02 for attenuation.CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.

  3. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Costa, Fernando Ferreira [Universidade Estadual de Campinas, Campinas, SP (Brazil); Silveira, Paulo Augusto Achucarro [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Wood, John [University of Southern California, California (United States); Hamerschlak, Nelson [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2013-07-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

  4. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging.

    Science.gov (United States)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles; Costa, Fernando Ferreira; Silveira, Paulo Augusto Achucarro; Wood, John; Hamerschlak, Nelson

    2013-12-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

  5. Fully automatic multi-atlas segmentation of CTA for partial volume correction in cardiac SPECT/CT

    Science.gov (United States)

    Liu, Qingyi; Mohy-ud-Din, Hassan; Boutagy, Nabil E.; Jiang, Mingyan; Ren, Silin; Stendahl, John C.; Sinusas, Albert J.; Liu, Chi

    2017-05-01

    Anatomical-based partial volume correction (PVC) has been shown to improve image quality and quantitative accuracy in cardiac SPECT/CT. However, this method requires manual segmentation of various organs from contrast-enhanced computed tomography angiography (CTA) data. In order to achieve fully automatic CTA segmentation for clinical translation, we investigated the most common multi-atlas segmentation methods. We also modified the multi-atlas segmentation method by introducing a novel label fusion algorithm for multiple organ segmentation to eliminate overlap and gap voxels. To evaluate our proposed automatic segmentation, eight canine 99mTc-labeled red blood cell SPECT/CT datasets that incorporated PVC were analyzed, using the leave-one-out approach. The Dice similarity coefficient of each organ was computed. Compared to the conventional label fusion method, our proposed label fusion method effectively eliminated gaps and overlaps and improved the CTA segmentation accuracy. The anatomical-based PVC of cardiac SPECT images with automatic multi-atlas segmentation provided consistent image quality and quantitative estimation of intramyocardial blood volume, as compared to those derived using manual segmentation. In conclusion, our proposed automatic multi-atlas segmentation method of CTAs is feasible, practical, and facilitates anatomical-based PVC of cardiac SPECT/CT images.

  6. The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

    Science.gov (United States)

    Smerup, Morten; Damkjær, Mads; Brøndum, Emil; Baandrup, Ulrik T; Kristiansen, Steen Buus; Nygaard, Hans; Funder, Jonas; Aalkjær, Christian; Sauer, Cathrine; Buchanan, Rasmus; Bertelsen, Mads Frost; Østergaard, Kristine; Grøndahl, Carsten; Candy, Geoffrey; Hasenkam, J Michael; Secher, Niels H; Bie, Peter; Wang, Tobias

    2016-02-01

    Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output. © 2016. Published by The Company of Biologists Ltd.

  7. Fusion of 4D echocardiography and cine cardiac magnetic resonance volumes using a salient spatio-temporal analysis

    Science.gov (United States)

    Atehortúa, Angélica; Garreau, Mireille; Romero, Eduardo

    2017-11-01

    An accurate left (LV) and right ventricular (RV) function quantification is important to support evaluation, diagnosis and prognosis of cardiac pathologies such as the cardiomyopathies. Currently, diagnosis by ultrasound is the most cost-effective examination. However, this modality is highly noisy and operator dependent, hence prone to errors. Therefore, fusion with other cardiac modalities may provide complementary information and improve the analysis of the specific pathologies like cardiomyopathies. This paper proposes an automatic registration between two complementary modalities, 4D echocardiography and Magnetic resonance images, by mapping both modalities to a common space of salience where an optimal registration between them is estimated. The obtained matrix transformation is then applied to the MRI volume which is superimposed to the 4D echocardiography. Manually selected marks in both modalities are used to evaluate the precision of the superimposition. Preliminary results, in three evaluation cases, show the distance between these marked points and the estimated with the transformation is about 2 mm.

  8. Perioperative volume replacement in children undergoing cardiac surgery: albumin versus hydroxyethyl starch 130/0.4

    NARCIS (Netherlands)

    Hanart, Christophe; Khalife, Maher; de Villé, Andrée; Otte, Florence; de Hert, Stefan; van der Linden, Philippe

    2009-01-01

    OBJECTIVE: To compare 4% albumin with 6% hydroxyethyl starch (HES) 130/0.4 in terms of perioperative blood loss and intraoperative fluid requirements in children undergoing cardiac surgery. DESIGN: Prospective randomized study. SETTING: Single University Hospital. PATIENTS: Pediatric patients

  9. ω-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin

    Directory of Open Access Journals (Sweden)

    O'Shea Karen M

    2010-09-01

    Full Text Available Abstract Background Pathological left ventricular (LV hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine ω-3 polyunsaturated fatty acids (ω-3 PUFA up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1 assessed the effects of ω-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2 evaluated the role of adiponectin in mediating the effects of ω-3 PUFA in heart. Methods Wild type (WT and adiponectin-/- mice underwent transverse aortic constriction (TAC and were fed standard chow ± ω-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated. Results TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by ω-3 PUFA without increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with TAC, and did not respond to ω-3 PUFA. Conclusion These findings suggest ω-3 PUFA attenuates cardiac pathology in response to pressure overload independent of an elevation in adiponectin.

  10. Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Andreasen, Jo B; Christiansen, Kirsten

    2013-01-01

    . The aims of the present study were to investigate changes in coagulation profiles after paediatric cardiac surgery and the effect after ex-vivo addition of blood products and haemostatic agents. Coagulation profiles were evaluated by thromboelastometry (ROTEM) in 54 children before and immediately after......Bleeding complications after cardiac surgery are of particular importance in children because they are more prone to volume overload. To optimize haemostatic intervention, the coagulopathy has to be characterized, and knowledge about the effect of blood products and haemostatic agents is needed...

  11. Measurement of cardiac ventricular volumes using multidetector row computed tomography: comparison of two- and three-dimensional methods

    Energy Technology Data Exchange (ETDEWEB)

    Montaudon, M. [Hopital Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Universite Victor Segalen Bordeaux 2, Laboratoire d' Anatomie Medico-Chirurgicale Appliquee, Bordeaux (France); Laffon, E. [Hopital Haut-Leveque, Service de Medecine Nucleaire, Pessac (France); Berger, P. [Universite Victor Segalen Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire C.R.I. INSERM 9806, Bordeaux (France); Corneloup, O.; Latrabe, V. [Hopital Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Laurent, F. [Hopital Haut-Leveque, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France); Universite Victor Segalen Bordeaux 2, Departement de Radiologie, Bordeaux (France)

    2006-10-15

    This study compared a three-dimensional volumetric threshold-based method to a two-dimensional Simpson's rule based short-axis multiplanar method for measuring right (RV) and left ventricular (LV) volumes, stroke volumes, and ejection fraction using electrocardiography-gated multidetector computed tomography (MDCT) data sets. End-diastolic volume (EDV) and end-systolic volume (ESV) of RV and LV were measured independently and blindly by two observers from contrast-enhanced MDCT images using commercial software in 18 patients. For RV and LV the three-dimensionally calculated EDV and ESV values were smaller than those provided by two-dimensional short axis (10%, 5%, 15% and 26% differences respectively). Agreement between the two methods was found for LV (EDV/ESV: r=0.974/0.910, ICC=0.905/0.890) but not for RV (r=0.882/0.930, ICC=0.663/0.544). Measurement errors were significant only for EDV of LV using the two-dimensional method. Similar reproducibility was found for LV measurements, but the three-dimensional method provided greater reproducibility for RV measurements than the two-dimensional. The threshold value supported three-dimensional method provides reproducible cardiac ventricular volume measurements, comparable to those obtained using the short-axis Simpson based method. (orig.)

  12. Clinical practice guide for the choice of perioperative volume-restoring fluid in adult patients undergoing non-cardiac surgery.

    Science.gov (United States)

    Basora, M; Colomina, M J; Moral, V; Asuero de Lis, M S; Boix, E; Jover, J L; Llau, J V; Rodrigo, M P; Ripollés, J; Calvo Vecino, J M

    2016-01-01

    The present Clinical practice guide responds to the clinical questions about security in the choice of fluid (crystalloid, colloid or hydroxyethyl starch 130) in patients who require volume replacement during perioperative period of non-cardiac surgeries. From the evidence summary, recommendations were made following the GRADE methodology. In this population fluid therapy based on crystalloids is suggested (weak recommendation, low quality evidence). In the events where volume replacement is not reached with crystalloids, the use of synthetic colloids (hydroxyethyl starch 130 or modified fluid gelatin) is suggested instead of 5% albumin (weak recommendation, low quality evidence). The choice and dosage of the colloid should be based in the product characteristics, patient comorbidity and anesthesiologist's experience. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Total bile acid levels are associated with left atrial volume and cardiac output in patients with cirrhosis

    DEFF Research Database (Denmark)

    Voiosu, Andrei M; Wiese, Signe; Voiosu, Theodor A

    2018-01-01

    BACKGROUND AND AIMS: Bile acids (BAs) are potent signaling molecules involved in the regulation of several metabolic and functional aspects of cardiovascular homeostasis. BA pool alteration in cirrhosis may contribute toward the development of hemodynamic and cardiac disturbances. We aimed...... and diastolic dysfunction were rare in the cohort. Total BA levels associated with several echocardiographic parameters of the hyperdynamic syndrome in univariate analysis but only with left atrial volume in multivariate analysis (P=0.007). BA concentrations did not differ according to the presence...... of echocardiographically diagnosed cirrhotic cardiomyopathy in the two models tested. CONCLUSION: Total serum BA levels are associated with enlarged left atrial volume and markers of the hyperdynamic circulation in patients with cirrhosis irrespective of the etiology or the severity of liver disease....

  14. Utility of intracardiac echocardiography for catheter ablation of complex cardiac arrhythmias in a medium-volume training center.

    Science.gov (United States)

    Filgueiras-Rama, David; de Torres-Alba, Fernando; Castrejón-Castrejón, Sergio; Estrada, Alejandro; Figueroa, Jorge; Salvador-Montañés, Óscar; López, Teresa; Moreno-Yanguela, Mar; López Sendón, José L; Merino, José L

    2015-04-01

    New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures. © 2014, Wiley Periodicals, Inc.

  15. Genetics Home Reference: African iron overload

    Science.gov (United States)

    ... beer develop African iron overload , and not all individuals of African descent with iron overload drink the beer. Therefore, researchers are seeking genetic differences that affect the risk of developing this condition. ...

  16. Information overload in medical practice.

    Science.gov (United States)

    Zeldes, Nathan; Baum, Neil

    2011-01-01

    Most practices are inundated with an excess of information. This information overload, or "infoglut," results in distractions and a loss of productivity. This article will discuss the concept of infoglut and what every practice can do to manage the tsunami of information that threatens to consume our practices.

  17. Changes in superior mesenteric artery Doppler waveform during reduction of cardiac stroke volume and hypotension

    DEFF Research Database (Denmark)

    Perko, M J; Perko, Grazyna; Just, S

    1996-01-01

    Influence of stroke volume reduction and hypotension on the superior mesenteric artery (SMA) Doppler waveform was evaluated during head-up tilt-induced central hypovolemia in 11 healthy volunteers. During normotensive reduction in stroke volume, peak systolic velocity (pV), mean velocity, pulsati......Influence of stroke volume reduction and hypotension on the superior mesenteric artery (SMA) Doppler waveform was evaluated during head-up tilt-induced central hypovolemia in 11 healthy volunteers. During normotensive reduction in stroke volume, peak systolic velocity (pV), mean velocity...

  18. A novel hydroxyethyl starch (Voluven (R)) for effective perioperative plasma volume substitution in cardiac surgery

    NARCIS (Netherlands)

    Huet, RCGG; Siemons, AW; Baus, D; van Rooyen-Butijn, WT; Haagenaars, JAM; van Oeveren, W; Bepperling, F

    2000-01-01

    Purpose: To compare the new hydroxyethyl starch HES 130/0.4 (Voluven(R)) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery. Methods: Fifty-nine patients scheduled for coronary artery bypass grafting were

  19. Cardiac adaptation to pregnancy in women with a history of preeclampsia and a subnormal plasma volume.

    NARCIS (Netherlands)

    Andrietti, S.; Kruse, A.J.; Bekkers, S.C.; Sep, S.; Spaanderman, M.E.A.; Peeters, L.L.

    2008-01-01

    In former preeclamptics, a subnormal plasma volume (LPV) predisposes to hemodynamic maladaptation to pregnancy. Here, we assessed the initial cardiovascular response to pregnancy in LPV (n = 20), in former preeclamptics with normal plasma volume (NPV) (n = 35) and in parous controls (CONTR) (n = 9)

  20. Non-invasive cardiac output monitoring for cesarean delivery under epidural anesthesia in a patient with Marfan syndrome and cardiomyopathy.

    Science.gov (United States)

    Beaudry, S; Pick, J; Heerdt, P M

    2016-02-01

    Maternal cardiac output and stroke volume increase significantly at the time of cesarean delivery. Parturients with baseline myocardial dysfunction are at increased risk of cardiovascular decompensation in the peripartum period and close hemodynamic monitoring is warranted. We report our use of intraoperative non-invasive cardiac output monitoring during cesarean delivery under epidural anesthesia in a 24-year-old woman with dilated cardiomyopathy secondary to Marfan syndrome, aortic arch, aortic valve and mitral valve replacements and a left ventricular ejection fraction of 37%. Three distinct hemodynamic trends were noted. After achieving adequate surgical anesthesia with 2% lidocaine 20mL, cardiac output and stroke volume rose for approximately 20min from baseline values of 6.3L/min and 69mL, respectively, to 9L/min and 107mL. Values subsequently trended down and remained depressed for nearly 20min following delivery. The lack of immediate post-delivery increases in both cardiac output and stroke volume were attributed to acute blood loss, intravascular volume depletion from fluid restriction, and slow infusion of oxytocin. By the end of surgery, cardiac output and stroke volume ultimately increased by 66% and 84% of baseline values, respectively. Systemic blood pressure, heart rate and cardiac output did not appear to correlate despite the use of phenylephrine to manage hypotension. The patient remained hemodynamically stable with no evidence of acute volume overload. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Cardiac catheterization

    Science.gov (United States)

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; ...

  2. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium–calcium overload

    OpenAIRE

    Noble, D; Noble, P J

    2006-01-01

    Late sodium current in cardiac cells is very small compared with the fast component, but as it flows throughout the action potential it may make a substantial contribution to sodium loading during each cardiac cycle. Late sodium current may contribute to triggering arrhythmia in two ways: by causing repolarisation failure (early afterdepolarisations); and by triggering late afterdepolarisations attributable to calcium oscillations in sodium–calcium overload conditions. Reduction of late sodiu...

  3. Unobtrusive Estimation of Cardiac Contractility and Stroke Volume Changes Using Ballistocardiogram Measurements on a High Bandwidth Force Plate

    Directory of Open Access Journals (Sweden)

    Hazar Ashouri

    2016-05-01

    Full Text Available Unobtrusive and inexpensive technologies for monitoring the cardiovascular health of heart failure (HF patients outside the clinic can potentially improve their continuity of care by enabling therapies to be adjusted dynamically based on the changing needs of the patients. Specifically, cardiac contractility and stroke volume (SV are two key aspects of cardiovascular health that change significantly for HF patients as their condition worsens, yet these parameters are typically measured only in hospital/clinical settings, or with implantable sensors. In this work, we demonstrate accurate measurement of cardiac contractility (based on pre-ejection period, PEP, timings and SV changes in subjects using ballistocardiogram (BCG signals detected via a high bandwidth force plate. The measurement is unobtrusive, as it simply requires the subject to stand still on the force plate while holding electrodes in the hands for simultaneous electrocardiogram (ECG detection. Specifically, we aimed to assess whether the high bandwidth force plate can provide accuracy beyond what is achieved using modified weighing scales we have developed in prior studies, based on timing intervals, as well as signal-to-noise ratio (SNR estimates. Our results indicate that the force plate BCG measurement provides more accurate timing information and allows for better estimation of PEP than the scale BCG (r2 = 0.85 vs. r2 = 0.81 during resting conditions. This correlation is stronger during recovery after exercise due to more significant changes in PEP (r2 = 0.92. The improvement in accuracy can be attributed to the wider bandwidth of the force plate. ∆SV (i.e., changes in stroke volume estimations from the force plate BCG resulted in an average error percentage of 5.3% with a standard deviation of ±4.2% across all subjects. Finally, SNR calculations showed slightly better SNR in the force plate measurements among all subjects but the small difference confirmed that SNR is

  4. Myocardial extracellular volume fraction from T1 measurements in healthy volunteers and mice: relationship to aging and cardiac dimensions.

    Science.gov (United States)

    Neilan, Tomas G; Coelho-Filho, Otavio R; Shah, Ravi V; Abbasi, Siddique A; Heydari, Bobak; Watanabe, Eri; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond Y; Jerosch-Herold, Michael

    2013-06-01

    This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. In healthy volunteers (N = 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r = 0.74, p volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. The Myocardial Extracellular Volume Fraction from T1 Measurements in Healthy Volunteers and Mice; Relationship to Aging and Cardiac Dimensions

    Science.gov (United States)

    Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Watanabe, Eri; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond; Jerosch-Herold, Michael

    2013-01-01

    Objectives We aimed to test the characteristics of the myocardial extracellular volume (ECV) fraction derived from pre and post-contrast T1 measurements among healthy volunteers. Background Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Methods Healthy volunteers underwent a standard CMR with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, inter-slice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol and cardiac sections were harvested for measurement of fibrosis. Results In healthy volunteers (n=32, 56% female; ages 21 to 72), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intra-class coefficients for the intra-observer, inter-observer, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval, 0.84 to 0.98), 0.93 (95% confidence interval, 0.80 to 0.98), and 0.95 (95% confidence interval, 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r=0.74, pvolunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, LA volume, and LV mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. PMID:23643283

  6. Atrial function, atrial volume and cardiovascular clinical outcomes in patients with end-stage renal disease - A study of cardiac computed tomography

    DEFF Research Database (Denmark)

    Dupont, Laust; Winther, Simon; Jørgensen, Hanne Skou

    2017-01-01

    candidates (n = 117) underwent contrast-enhanced CT screening for coronary artery disease as part of the work-up prior to kidney transplantation before being accepted on the transplantation waiting list. Left atrial (LA) and left ventricular (LV) volume and function were determined by cardiac CT. MACE......-enhanced cardiac CT may offers a more precise measure of atrial dimensions and function than 2-dimensional echocardiography and may provide improved predictionof patient outcome. AIM: The aim of the present study was to examine the association of LAEDV and left atrial ejection fraction (LAEF) assessed by CT...... with left ventricle end-diastolic volume (LVEDV), left ventricular mass, left ventricular ejection fraction and N-terminal plasma-pro-brain natriuretic peptide (NT-PRO-BNP). Furthermore, we examined LAEDV and LAEF as predictors of major adverse cardiac events (MACE) and mortality. METHODS: Kidney transplant...

  7. Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume decrease and is this influenced by deletion of PLM?

    Science.gov (United States)

    Bell, James R; Lloyd, David; Curl, Claire L; Delbridge, Lea M D; Shattock, Michael J

    2009-03-01

    In addition to modulatory actions on Na+-K+-ATPase, phospholemman (PLM) has been proposed to play a role in cell volume regulation. Overexpression of PLM induces ionic conductances, with 'PLM channels' exhibiting selectivity for taurine. Osmotic challenge of host cells overexpressing PLM increases taurine efflux and augments the cellular regulatory volume decrease (RVD) response, though a link between PLM and cell volume regulation has not been studied in the heart. We recently reported a depressed cardiac contractile function in PLM knockout mice in vivo, which was exacerbated in crystalloid-perfused isolated hearts, indicating that these hearts were osmotically challenged. To address this, the present study investigated the role of PLM in osmoregulation in the heart. Isolated PLM wild-type and knockout hearts were perfused with a crystalloid buffer supplemented with mannitol in a bid to prevent perfusate-induced cell swelling and maintain function. Accordingly, and in contrast to wild-type control hearts, contractile function was improved in PLM knockout hearts with 30 mM mannitol. To investigate further, isolated PLM wild-type and knockout cardiomyocytes were subjected to increasing hyposmotic challenges. Initial validation studies showed the IonOptix video edge-detection system to be a simple and accurate 'real-time' method for tracking cell width as a marker of cell size. Myocytes swelled equally in both genotypes, indicating that PLM, when expressed at physiological levels in cardiomyocytes, is not essential to limit water accumulation in response to a hyposmotic challenge. Interestingly, freshly isolated adult cardiomyocytes consistently failed to mount RVDs in response to cell swelling, adding to conflicting reports in the literature. A proposed perturbation of the RVD response as a result of the cell isolation process was not restored, however, with short-term culture in either adult or neonatal cardiomyocytes.

  8. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure.

    Science.gov (United States)

    Oka, Toru; Akazawa, Hiroshi; Naito, Atsuhiko T; Komuro, Issei

    2014-01-31

    Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell-cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure.

  9. Phospholemman: a novel cardiac stress protein.

    Science.gov (United States)

    Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E; Chan, Tung O; Wang, Jufang

    2010-08-01

    Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196.

  10. Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET

    Directory of Open Access Journals (Sweden)

    Jonny Nordström

    2017-11-01

    Full Text Available Abstract Background Quantitative measurement of myocardial blood flow (MBF is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD. 15O-water positron emission tomography (PET is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV volumes and ejection fraction (EF is not possible from standard 15O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B 15O-water images and from first pass (FP images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated 15O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV, end-diastolic volume (EDV, stroke volume (SV and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI. Results Using V B images, high correlations between PET and MRI ESV (r = 0.89, p  0.86, p < 0.001. Conclusion Calculation of LV volumes and LVEF from dynamic 15O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.

  11. Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease (World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From Chest CT Imaging.

    Science.gov (United States)

    Aviram, Galit; Rozenbaum, Zach; Ziv-Baran, Tomer; Berliner, Shlomo; Topilsky, Yan; Fleischmann, Dominik; Sung, Yon K; Zamanian, Roham T; Guo, Haiwei Henry

    2017-10-01

    Evaluations of patients with pulmonary hypertension (PH) commonly include chest CT imaging. We hypothesized that cardiac chamber volumes calculated from the same CT scans can yield additional information to distinguish PH related to left-sided heart disease (World Health Organization group 2) from other PH subtypes. Patients who had PH confirmed by right heart catheterization and contrast-enhanced chest CT studies were enrolled in this retrospective multicenter study. Cardiac chamber volumes were calculated using automated segmentation software and compared between group 2 and non-group 2 patients with PH. This study included 114 patients with PH, 27 (24%) of whom were classified as group 2 based on their pulmonary capillary wedge pressure. Patients with group 2 PH exhibited significantly larger median left atrial (LA) volumes (118 mL vs 63 mL; P heart disease. Copyright © 2017. Published by Elsevier Inc.

  12. Update on the use of deferasirox in the management of iron overload

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-10-01

    Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

  13. Simultaneous His Bundle and Left Ventricular Pacing for Optimal Cardiac Resynchronization Therapy Delivery: Acute Hemodynamic Assessment by Pressure-Volume Loops.

    Science.gov (United States)

    Padeletti, Luigi; Pieragnoli, Paolo; Ricciardi, Giuseppe; Innocenti, Lisa; Checchi, Luca; Padeletti, Margherita; Michelucci, Antonio; Picariello, Francesco; Valsecchi, Sergio

    2016-05-01

    Previous studies have investigated the role of intrinsic conduction in optimizing cardiac resynchronization therapy. We investigated the role of fusing pacing-induced activation and intrinsic conduction in cardiac resynchronization therapy by evaluating the acute hemodynamic effects of simultaneous His-bundle (HIS) and left ventricular (LV) pacing. We studied 11 patients with systolic heart failure and left bundle-branch block scheduled for cardiac resynchronization therapy implantation. On implantation, LV pressure-volume data were determined via conductance catheter. Standard leads were placed in the right atrium, at the right ventricular apex, and in a coronary vein. An additional electrode was temporarily positioned in the HIS. The following pacing configurations were systematically assessed: standard biventricular (right ventricular apex+LV), LV-only, HIS, simultaneous HIS and LV (HIS+LV). Each configuration was compared with the AAI mode at multiple atrioventricular delays (AVD). In comparison with the AAI, right ventricular apex+LV and LV-only pacing resulted in improved stroke volume (85±32 mL and 86±33 mL versus 58±23 mL; PHIS-LV pacing improved hemodynamic indexes at all AVD (stroke volume >76 mL at all fixed intervals and 88±31 mL at optimal interval; all PHIS+LV pacing yielded improvements, regardless of AVD setting. These findings support the hypothesis of the crucial role of intrinsic right ventricular conduction in optimal cardiac resynchronization therapy delivery. © 2016 American Heart Association, Inc.

  14. A three-dimensional model-based partial volume correction strategy for gated cardiac mouse PET imaging

    Science.gov (United States)

    Dumouchel, Tyler; Thorn, Stephanie; Kordos, Myra; DaSilva, Jean; Beanlands, Rob S. B.; deKemp, Robert A.

    2012-07-01

    Quantification in cardiac mouse positron emission tomography (PET) imaging is limited by the imaging spatial resolution. Spillover of left ventricle (LV) myocardial activity into adjacent organs results in partial volume (PV) losses leading to underestimation of myocardial activity. A PV correction method was developed to restore accuracy of the activity distribution for FDG mouse imaging. The PV correction model was based on convolving an LV image estimate with a 3D point spread function. The LV model was described regionally by a five-parameter profile including myocardial, background and blood activities which were separated into three compartments by the endocardial radius and myocardium wall thickness. The PV correction was tested with digital simulations and a physical 3D mouse LV phantom. In vivo cardiac FDG mouse PET imaging was also performed. Following imaging, the mice were sacrificed and the tracer biodistribution in the LV and liver tissue was measured using a gamma-counter. The PV correction algorithm improved recovery from 50% to within 5% of the truth for the simulated and measured phantom data and image uniformity by 5-13%. The PV correction algorithm improved the mean myocardial LV recovery from 0.56 (0.54) to 1.13 (1.10) without (with) scatter and attenuation corrections. The mean image uniformity was improved from 26% (26%) to 17% (16%) without (with) scatter and attenuation corrections applied. Scatter and attenuation corrections were not observed to significantly impact PV-corrected myocardial recovery or image uniformity. Image-based PV correction algorithm can increase the accuracy of PET image activity and improve the uniformity of the activity distribution in normal mice. The algorithm may be applied using different tracers, in transgenic models that affect myocardial uptake, or in different species provided there is sufficient image quality and similar contrast between the myocardium and surrounding structures.

  15. Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study.

    Science.gov (United States)

    Zhang, Jian; Chen, Chao Qin; Lei, Xiu Zhen; Feng, Zhi Ying; Zhu, Sheng Mei

    2013-07-01

    This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation.

  16. Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea.

    Science.gov (United States)

    Mackenzie, C F; Skacel, M; Barnas, G M; Brampton, W J; Alana, C A

    1990-05-01

    We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.

  17. Intelligent Overload Control for Composite Web Services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Zivkovic, Miroslav; Meeuwissen, H.B.; Gijsen, B.M.M.

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  18. Intelligent overload control for composite web services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Živković, M.; Meeuwissen, H.B.; Gijsen, B.M.M.

    2009-01-01

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  19. Intelligent Overload Control for Composite Web Services

    NARCIS (Netherlands)

    Meulenhoff, P.J.; Ostendorf, D.R.; Zivkovic, Miroslav; Meeuwissen, H.B.; Gijsen, B.M.M.

    2009-01-01

    In this paper, we analyze overload control for composite web services in service oriented architectures by an orchestrating broker, and propose two practical access control rules which effectively mitigate the effects of severe overloads at some web services in the composite service. These two rules

  20. A Test of the Urban Overload Hypothesis.

    Science.gov (United States)

    McCauley, Clark R.

    This paper briefly discusses three studies aimed at exploring the overload hypothesis posited by Stanley Milgram. That hypothesis suggests that impoverished social interaction in the city is an adaptation to overload of interpersonal contacts. The three studies examine various aspects of the phenomenon using different methodologies. Comparing city…

  1. Epicardial fat volume and aortic stiffness in healthy individuals. A quantitative cardiac magnetic resonance study

    Energy Technology Data Exchange (ETDEWEB)

    Homsi, R.; Thomas, D.; Meier-Schroers, M.; Dabir, D.; Kuetting, D.; Luetkens, J.A.; Marx, C.; Schild, H.H. [Bonn University Hospital (Germany). Radiology; Gieseke, J. [Philips Healthcare, Hamburg (Germany); Sprinkart, A. [Bonn University Hospital (Germany). Radiology; Bochum Univ. (Germany). Inst. of Medical Engineering

    2016-09-15

    To determine epicardial fat volume (EFV) and aortic stiffness (assessed by aortic pulse wave velocity (PWV)) in healthy individuals, and to investigate the relationship of these parameters, and their association with body mass index (BMI) and age. 58 subjects (29 men, mean age 44.7 ± 13.9 years[y]) underwent a CMR exam at 1.5 Tesla. A 2 D velocity-encoded CMR scan was acquired to determine PWV. The EFV was measured based on a 3 D-mDixon sequence. Group comparisons were made between younger (age < 45y; n=30; mean age 33.4 ± 6.6y) and older (> 45y; n=28; 56.7 ± 8.4y) subjects and between subjects with a BMI < 25 kg/m{sup 2} (n=28; BMI 21.9 ± 2.5 kg/m{sup 2}) and a BMI > 25 kg/m{sup 2} (n=30; 28.7 ± 4.0 kg/m{sup 2}). Associations between the determined parameters were assessed by analyses of covariance (ANCOVAs). The mean values of PWV and EFV (normalized to body surface area) were 6.9 ±1.9 m/s and 44.2 ± 25.0 ml/m{sup 2}, respectively. The PWV and EFV were significantly higher in the older group (PWV=7.9 ± 2.0 m/s vs. 6.0 ± 1.2 m/s; EFV=54.7 ml/m{sup 2} vs. 34.5 ml/m{sup 2}; p < 0.01, each), with no significant differences in BMI or sex. In the overweighted group the EFV was significantly higher than in subjects with a BMI < 25kg/m{sup 2} (EFV=56.1 ± 27.1 ml/m{sup 2} vs. 31.5 ± 14.6 ml/m{sup 2}; p < 0.01) but without a significant difference in PWV. ANCOVA revealed a significant correlation between EFV and PWV, also after adjustment for age (p=0.025). An association was found between age and EFV as well as PWV. EFV and PWV were related to each other also after adjustment for age. The metabolic and pro-inflammatory activity found with increased epicardial fat volume may promote the development of atherosclerosis and aortic stiffness. CMR may be valuable for future studies investigating the relationship between EFV and PWV in patients with increased cardiovascular risk.

  2. Normal values of left ventricularmass and cardiac chamber volumes assessed by 320-detector computed tomography angiography in the Copenhagen General Population Study

    DEFF Research Database (Denmark)

    Fuchs, Andreas; Mejdahl, Mads Rams; Kühl, J Tobias

    2016-01-01

    age was 55 (range: 40-84) years, and 188 (33%) were men. BSA-indexed 97.5th percentile cut-off values: LVM 80 and 65 gr/m2, left ventricular volume 97 and 83 mL/m2, right ventricular volume 120 and 102 mL/m2, left atrial volume 60 and 57 mL/m2, and right atrial volume 85 and 73 mL/m2 for men and women......, respectively. Men had greater absolute and indexed LVM and chamber volumes than women. For both genders, indexed ventricular volumes declined, whereas indexed atrial volumes increased in advancing age groups. For men, indexed LVM declined in advancing age groups. In multivariate analyses, gender, BSA, systolic...... blood pressure, and hard physical activity accounted for 63% of variance in LVM. Conclusion In this cross-sectional general population study, men have greater indexed LVM and chamber volumes than women, and cardiac indexed volumes vary between age groups in both genders. These findings demonstrate...

  3. Late Cardiac Toxicity After Mediastinal Radiation Therapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction.

    Science.gov (United States)

    Hahn, Ezra; Jiang, Haiyan; Ng, Angela; Bashir, Shaheena; Ahmed, Sameera; Tsang, Richard; Sun, Alexander; Gospodarowicz, Mary; Hodgson, David

    2017-08-01

    Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry. A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries. There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, Pheart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior. Copyright

  4. Atrial function, atrial volume and cardiovascular clinical outcomes in patients with end-stage renal disease - A study of cardiac computed tomography

    DEFF Research Database (Denmark)

    Rasmussen, Laust Dupont; Winther, Simon; Jørgensen, Hanne Skou

    2017-01-01

    BACKGROUND: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular events. Previous studies using 2-dimensional echocardiography show that left atrial end-diastolic volume (LAEDV) predicts cardiovascular outcomes and mortality in patients with CKD. However, contrast...... candidates (n = 117) underwent contrast-enhanced CT screening for coronary artery disease as part of the work-up prior to kidney transplantation before being accepted on the transplantation waiting list. Left atrial (LA) and left ventricular (LV) volume and function were determined by cardiac CT. MACE...

  5. Extracellular volume quantification by cardiac magnetic resonance imaging without hematocrit sampling : Ready for prime time?

    Science.gov (United States)

    Kammerlander, Andreas A; Duca, Franz; Binder, Christina; Aschauer, Stefan; Zotter-Tufaro, Caroline; Koschutnik, Matthias; Marzluf, Beatrice A; Bonderman, Diana; Mascherbauer, Julia

    2017-10-04

    Myocardial tissue characterization by cardiovascular magnetic resonance (CMR) T1 mapping currently receives increasing interest as a diagnostic tool in various disease settings. The T1-mapping technique allows non-invasive estimation of myocardial extracellular volume (ECV) using T1-times before and after gadolinium administration; however, for calculation of the myocardial ECV the hematocrit is needed, which limits its utility in routine application. Recently, the alternative use of the blood pool T1-time instead of the hematocrit has been described. The results of CMR T1 mapping data of 513 consecutive patients were analyzed for this study. Blood for hematocrit measurement was drawn when placing the i. v. line for contrast agent administration. Data from the first 200 consecutive patients (derivation cohort) were used to establish a regression formula allowing synthetic hematocrit calculation, which was then validated in the following 313 patients (validation cohort). Synthetic ECV was calculated using synthetic hematocrit, and was compared with conventionally derived ECV. Among the entire cohort of 513 patients (mean age 57.4 ± 17.5 years old, 49.1% female) conventionally measured hematocrit was 39.9 ± 4.7% and native blood pool T1-time was 1570.6 ± 117.8 ms. Hematocrit and relaxivity of blood (R1 = 1/blood pool T1 time) were significantly correlated (r = 0.533, r(2) = 0.284, p ECV showed significant correlation in the validation (r = 0.533, r(2) = 0.284, p ECV was found in the validation cohort (mean difference: 0.007%, limits of agreement: -4.32 and 4.33%, respectively). Synthetic ECV using native blood pool T1-times to calculate the hematocrit, is feasible and leads to almost identical results in comparison with the conventional method. It may allow fully automatic ECV-mapping and thus enable broader use of ECV by CMR T1 mapping in clinical practice.

  6. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

    Directory of Open Access Journals (Sweden)

    Chalmers AW

    2016-02-01

    Full Text Available Anna W Chalmers, Jamile M Shammo Department of Internal Medicine, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelodysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. Keywords: iron chelation therapy, transfusional iron overload, deferasirox

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

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

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

  8. 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.

  9. Changes in cardiac pumping efficiency and intra-thoracic organ volume during negative pressure wound therapy of sternotomy wounds, assessment using magnetic resonance imaging.

    Science.gov (United States)

    Torbrand, Christian; Ugander, Martin; Engblom, Henrik; Olivecrona, Göran K; Gålne, Olof; Arheden, Håkan; Ingemansson, Richard; Malmsjö, Malin

    2010-08-01

    Knowledge on the effects of negative pressure wound therapy (NPWT) on the intra-thoracic organs is limited. The present study was performed to investigate the effects of NPWT on the volume of the intra-thoracic organs, using magnetic resonance imaging (MRI), in a porcine sternotomy wound model. Six pigs underwent median sternotomy followed by NPWT at -75, -125 and -175 mmHg. Six pigs were not sternotomised. MR images covering the thorax and heart were acquired. The volumes of the thoracic cavity, lungs, wound fluid and heart were then determined. The volumes of the thoracic cavity and intra-thoracic organs increased after sternotomy and decreased upon NPWT application. The total heart volume variation, which is inversely related to cardiac pumping efficiency, was higher after sternotomy and decreased during NPWT. NPWT did not result in the evacuation of wound fluid from the bottom of the wound. NPWT largely closes and restores the thoracic cavity. Cardiac pumping efficiency returns to pre-sternotomy levels during NPWT. This may contribute to the clinical benefits of NPWT over open-chest care, including the stabilizing effects and the reduced need for mechanical ventilation.

  10. Thermal Characterization of the Overload Carbon Resistors

    Directory of Open Access Journals (Sweden)

    Ivana Kostić

    2013-01-01

    Full Text Available In many applications, the electronic component is not continuously but only intermittently overloaded (e.g., inrush current, short circuit, or discharging interference. With this paper, we provide insight into carbon resistors that have to hold out a rarely occurring transient overload. Using simple electrical circuit, the resistor is overheating with higher current than declared, and dissipation is observed by a thermal camera.

  11. Carvedilol and Its New Analogs Suppress Arrhythmogenic Store Overload-induced Ca2+ Release

    OpenAIRE

    Zhou, Qiang; Xiao, Jianmin; Jiang, Dawei; Wang, Ruiwu; Vembaiyan, Kannan; Wang, Aixia; Smith, Chris D.; Xie, Cuihong; Chen, Wenqian; Zhang, Jingqun; Tian, Xixi; Jones, Peter P.; Zhong, Xiaowei; Guo, Ang; Chen, Haiyan

    2011-01-01

    Carvedilol is one of the most effective beta-blockers for preventing ventricular tachyarrhythmias (VTs) in heart failure (HF), but the mechanisms underlying its favorable anti-arrhythmic benefits remain unclear. Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), are known to evoke VTs in patients with HF. Here we show that carvedilol is the only beta-blocker that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor...

  12. Unravelling the grey zone : Cardiac MRI volume to wall mass ratio to differentiate hypertrophic cardiomyopathy and the athlete's heart

    NARCIS (Netherlands)

    Luijkx, Tim; Cramer, Maarten J.; Buckens, Stan; Zaidi, Abbas; Rienks, R; Mosterd, Arend; Prakken, Niek H J; Dijkman, Barbara; Mali, W.P.; Velthuis, BK

    2015-01-01

    Background Differentiating physiological left ventricular hypertrophy (LVH) in athletes from pathological hypertrophic cardiomyopathy (HCM) can be challenging. This study assesses the ability of cardiac MRI (CMR) to distinguish between physiological LVH (so-called athlete's heart) and HCM. Methods

  13. Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    2013-07-01

    Full Text Available OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting in thoracic surgery patients requiring one-lung ventilation.

  14. Cardiac hypertrophy in mice expressing unphosphorylatable phospholemman.

    Science.gov (United States)

    Boguslavskyi, Andrii; Pavlovic, Davor; Aughton, Karen; Clark, James E; Howie, Jacqueline; Fuller, William; Shattock, Michael J

    2014-10-01

    Elevation of intracellular Na in the failing myocardium contributes to contractile dysfunction, the negative force-frequency relationship, and arrhythmias. Although phospholemman (PLM) is recognized to form the link between signalling pathways and Na/K pump activity, the possibility that defects in its regulation contribute to elevation of intracellular Na has not been investigated. Our aim was to test the hypothesis that the prevention of PLM phosphorylation in a PLM(3SA) knock-in mouse (in which PLM has been rendered unphosphorylatable) will exacerbate cardiac hypertrophy and cellular Na overload. Testing this hypothesis should determine whether changes in PLM phosphorylation are simply bystander effects or are causally involved in disease progression. In wild-type (WT) mice, aortic constriction resulted in hypophosphorylation of PLM with no change in Na/K pump expression. This under-phosphorylation of PLM occurred at 3 days post-banding and was associated with a progressive decline in Na/K pump current and elevation of [Na]i. Echocardiography, morphometry, and pressure-volume (PV) catheterization confirmed remodelling, dilation, and contractile dysfunction, respectively. In PLM(3SA) mice, expression of Na/K ATPase was increased and PLM decreased such that net Na/K pump current under quiescent conditions was unchanged (cf. WT myocytes); [Na(+)]i was increased and forward-mode Na/Ca exchanger was reduced in paced PLM(3SA) myocytes. Cardiac hypertrophy and Na/K pump inhibition were significantly exacerbated in banded PLM(3SA) mice compared with banded WT. Decreased phosphorylation of PLM reduces Na/K pump activity and exacerbates Na overload, contractile dysfunction, and adverse remodelling following aortic constriction in mice. This suggests a novel therapeutic target for the treatment of heart failure. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  15. Cardiac Specific, Inducible ClC-3 Gene Deletion Eliminates Native Volume-Sensitive Chloride Channels and Produces Myocardial Hypertrophy in Adult Mice

    Science.gov (United States)

    Xiong, Dazhi; Heyman, Nathanael S.; Airey, Judith; Zhang, Mi; Singer, Cherie A.; Rawat, Shanti; Ye, Linda; Evans, Rebecca; Burkin, Dean J.; Tian, Honglin; McCloskey, Diana T; Valencik, Maria; Britton, Fiona C.; Duan, Dayue; Hume, Joseph R.

    2009-01-01

    Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells. To directly test this hypothesis, and assess the physiological role of ClC-3 in cardiac function, we generated a novel line of cardiac specific inducible ClC-3 knock-out mice. These transgenic mice were maintained on a doxycycline diet to preserve ClC-3 expression; removal of doxycycline activates Cre recombinase to inactivate the Clcn3 gene. Echocardiography revealed dramatically reduced ejection fraction and fractional shortening, and severe signs of myocardial hypertrophy and heart failure in the knock-out mice at both 1.5 and 3 weeks off doxycycline. In mice off doxyclycline, time-dependent inactivation of ClC-3 gene expression was confirmed in atrial and ventricular cells by qRT-PCR and Western blot analysis. Electrophysiological examination of native VSOACs in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of the currents, whereas at 1.5 weeks, VSOAC current densities were significantly reduced, compared to age-matched control mice maintained on doxycycline. These results indicate that ClC-3 is a key component of native VSOACs in mammalian heart and plays a significant cardioprotective role against cardiac hypertrophy and failure. PMID:19615374

  16. Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice.

    Science.gov (United States)

    Xiong, Dazhi; Heyman, Nathanael S; Airey, Judith; Zhang, Mi; Singer, Cherie A; Rawat, Shanti; Ye, Linda; Evans, Rebecca; Burkin, Dean J; Tian, Honglin; McCloskey, Diana T; Valencik, Maria; Britton, Fiona C; Duan, Dayue; Hume, Joseph R

    2010-01-01

    Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells. To directly test this hypothesis, and assess the physiological role of ClC-3 in cardiac function, we generated a novel line of cardiac-specific inducible ClC-3 knock-out mice. These transgenic mice were maintained on a doxycycline diet to preserve ClC-3 expression; removal of doxycycline activates Cre recombinase to inactivate the Clcn3 gene. Echocardiography revealed dramatically reduced ejection fraction and fractional shortening, and severe signs of myocardial hypertrophy and heart failure in the knock-out mice at both 1.5 and 3 weeks off doxycycline. In mice off doxycycline, time-dependent inactivation of ClC-3 gene expression was confirmed in atrial and ventricular cells by qRT-PCR and Western blot analysis. Electrophysiological examination of native VSOACs in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of the currents, whereas at 1.5 weeks, VSOAC current densities were significantly reduced, compared to age-matched control mice maintained on doxycycline. These results indicate that ClC-3 is a key component of native VSOACs in mammalian heart and plays a significant cardioprotective role against cardiac hypertrophy and failure. Copyright 2009 Elsevier Inc. All rights reserved.

  17. Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study.

    Science.gov (United States)

    Foppa, Murilo; Arora, Garima; Gona, Philimon; Ashrafi, Arman; Salton, Carol J; Yeon, Susan B; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Chuang, Michael L

    2016-03-01

    Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all Pheart rate account for most of the variability in RV volumes and function in this community-dwelling population. We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. © 2016 American Heart Association, Inc.

  18. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

  19. The association of willingness-to-pay and patient attributes: a cost-volume-profit analysis of cardiac catheter unit services in Ramallah Hospital, Palestine.

    Science.gov (United States)

    Jabr, Samer F K; Younis, Mustafa Mike Z; Forgione, Dana A

    2009-01-01

    The purpose of this study is to examine the association of willingness-to-pay and patient attributes in relation to the multi-service cost-volume-profit structure of a cardiac catheter unit in Ramallah Hospital. This article contributes to the literature by providing primary evidence on patient willingness-to-pay, by identifying the specific break-even parameters of three hospital cardiac catheter unit service types (diagnosis, balloon, and pacemaker), and by demonstrating the cross-subsidization of patient income groups that is inherent in the existing hospital rate structure. Our results provide information useful for (1) evidence-based policy making with respect to hospital rate setting and cross-subsidies of patient income groups; (2) the advancement of hospital management, by demonstrating the estimated variable and fixed cost parameters and the impact of patient revenue mix on the profitability of cardiac catheter unit services; and (3) the advancement of theory, by documenting the relationship of patient demand and the cost of supply in a multi-patient-group, multi-service hospital setting.

  20. [The use of gravitation overloading in the treatment of obliterative atherosclerosis of lower extremity arteries].

    Science.gov (United States)

    Galkin, R A; Kotel'nikov, G P; Makarov, I V; Oparin, A N

    2003-01-01

    The article sums up results of treatment of 152 patients with obliterating atherosclerosis of the lower extremity arteries which were exposed to 2-3 G gravitation overloading made in a centrifuge of a short radius in direction head--pelvis. The gravitation overloading in the regimen followed were not found to have negative effects of central hemodynamics. Peripheral circulation was noted to considerably improve which is confirmed: 1) by clinical data showing 2-5 times longer distance of painless walking; 2) by the data of ultrasound dopplerography manifested as larger volume rate of blood flow and regional perfusion index; 3) by thermographic explorations evidencing the recovery of the thermoprophile of the legs and feet. Thus, the application of gravitation overloading is a new effective method of conservative treatment of patients with the pathology in question.

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

    Directory of Open Access Journals (Sweden)

    Esther Zorio-Grima

    2013-01-01

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

  2. Ly6C(low) and not Ly6C(high) macrophages accumulate first in the heart in a model of murine pressure-overload.

    Science.gov (United States)

    Weisheit, Christina; Zhang, Yunyang; Faron, Anton; Köpke, Odilia; Weisheit, Gunnar; Steinsträsser, Arne; Frede, Stilla; Meyer, Rainer; Boehm, Olaf; Hoeft, Andreas; Kurts, Christian; Baumgarten, Georg

    2014-01-01

    Cardiac tissue remodeling in the course of chronic left ventricular hypertrophy requires phagocytes which degrade cellular debris, initiate and maintain tissue inflammation and reorganization. The dynamics of phagocytes in left ventricular hypertrophy have not been systematically studied. Here, we characterized the temporal accumulation of leukocytes in the cardiac immune response by flow cytometry and fluorescence microscopy at day 3, 6 and 21 following transverse aortic constriction (TAC). Cardiac hypertrophy due to chronic pressure overload causes cardiac immune response and inflammation represented by an increase of immune cells at all three time points among which neutrophils reached their maximum at day 3 and macrophages at day 6. The cardiac macrophage population consisted of both Ly6C(low) and Ly6C(high) macrophages. Ly6C(low) macrophages were more abundant peaking at day 6 in response to pressure overload. During the development of cardiac hypertrophy the expression pattern of adhesion molecules was investigated by qRT-PCR and flow cytometry. CD11b, CX3CR1 and ICAM-1 determined by qRT-PCR in whole cardiac tissue were up-regulated in response to pressure overload at day 3 and 6. CD11b and CX3CR1 were significantly increased by TAC on the surface of Ly6C(low) but not on Ly6C(high) macrophages. Furthermore, ICAM-1 was up-regulated on cardiac endothelial cells. In fluorescence microscopy Ly6C(low) macrophages could be observed attached to the intra- and extra-vascular vessel-wall. Taken together, TAC induced the expression of adhesion molecules, which may explain the accumulation of Ly6C(low) macrophages in the cardiac tissue, where these cells might contribute to cardiac inflammation and remodeling in response to pressure overload.

  3. Ly6C(low and not Ly6C(high macrophages accumulate first in the heart in a model of murine pressure-overload.

    Directory of Open Access Journals (Sweden)

    Christina Weisheit

    Full Text Available Cardiac tissue remodeling in the course of chronic left ventricular hypertrophy requires phagocytes which degrade cellular debris, initiate and maintain tissue inflammation and reorganization. The dynamics of phagocytes in left ventricular hypertrophy have not been systematically studied. Here, we characterized the temporal accumulation of leukocytes in the cardiac immune response by flow cytometry and fluorescence microscopy at day 3, 6 and 21 following transverse aortic constriction (TAC. Cardiac hypertrophy due to chronic pressure overload causes cardiac immune response and inflammation represented by an increase of immune cells at all three time points among which neutrophils reached their maximum at day 3 and macrophages at day 6. The cardiac macrophage population consisted of both Ly6C(low and Ly6C(high macrophages. Ly6C(low macrophages were more abundant peaking at day 6 in response to pressure overload. During the development of cardiac hypertrophy the expression pattern of adhesion molecules was investigated by qRT-PCR and flow cytometry. CD11b, CX3CR1 and ICAM-1 determined by qRT-PCR in whole cardiac tissue were up-regulated in response to pressure overload at day 3 and 6. CD11b and CX3CR1 were significantly increased by TAC on the surface of Ly6C(low but not on Ly6C(high macrophages. Furthermore, ICAM-1 was up-regulated on cardiac endothelial cells. In fluorescence microscopy Ly6C(low macrophages could be observed attached to the intra- and extra-vascular vessel-wall. Taken together, TAC induced the expression of adhesion molecules, which may explain the accumulation of Ly6C(low macrophages in the cardiac tissue, where these cells might contribute to cardiac inflammation and remodeling in response to pressure overload.

  4. Volume control in treatment-resistant congestive heart failure: role for peritoneal dialysis.

    Science.gov (United States)

    Broekman, K E; Sinkeler, S J; Waanders, F; Bartels, G L; Navis, G; Janssen, W M T

    2014-11-01

    Chronic congestive heart failure (HF) has a rising prevalence and increasing impact on health care systems. Current treatment consists of diuretics, renin-angiotensin-aldosterone system blockers, and restriction of salt and fluids. This strategy is often hampered by a drop in effective circulating volume and hence renal perfusion and function, triggering harmful counter regulatory mechanisms. Slow ultrafiltration by peritoneal dialysis (PD) might be an effective treatment strategy to relieve fluid overload without compromising cardiac output and thereby renal function. In this review, we discuss the (patho)physiological mechanisms of the cardiorenal interaction and the current literature on PD strategies in congestive HF.

  5. Cardiac chamber volumes, function, and mass as determined by 64-multidetector row computed tomography: mean values among healthy adults free of hypertension and obesity.

    Science.gov (United States)

    Lin, Fay Y; Devereux, Richard B; Roman, Mary J; Meng, Joyce; Jow, Veronica M; Jacobs, Avrum; Weinsaft, Jonathan W; Shaw, Leslee J; Berman, Daniel S; Callister, Tracy Q; Min, James K

    2008-11-01

    We derived mean values for cardiac dimensions, volumes, function, and mass in a normotensive nonobese population free of cardiovascular disease. Multidetector computed tomography (MDCT) permits study of cardiac chamber size, function, and mass. Age- and gender-specific mean values are not available. A total of 103 normotensive, nonobese adults (43% women, age 51 +/- 14 years) who presented consecutively to 2 medical centers for clinically indicated MDCTs with neither history of nor MDCT evidence of significant cardiovascular disease were studied for left ventricular (LV) and right ventricular (RV) end-systolic (ES) and end-diastolic (ED) linear dimensions and volumes; LV and RV ejection fraction (EF), and LV mass (LVM); and left atrial (LA) and right atrial (RA) end-systolic volumes (LAESV and RAESV, respectively) by 1-dimensional (1D), 2-dimensional (2D), and 3-dimensional (3D) measurements. The LV volumes using 3D techniques were lower than 2D techniques (LVEDV mean 144 +/- 71 ml vs. 150 +/- 70 ml), with higher LVEF (63 +/- 15% vs. 57 +/- 13%) (p < 0.001 for both). Mean LVM/height(2.7) was 24.3 +/- 11.0 g/m(2.7) and mean relative wall thickness was 0.16 to 0.44. Evaluation by 20 versus 10 cardiac phases resulted in higher LVEF (mean difference: 3.4 +/- 9.0%, p < 0.001). For LVEDV, interobserver (r = 0.99, p < 0.001) and intraobserver (r(2) = 0.97, p < 0.001) correlations were high. Mean RVEDV was 82 +/- 57 ml and RVEF was 58 +/- 16. The LAESV determined by 3D techniques was higher than by that determined by 2D methods (102 +/- 48 ml vs. 87 +/- 57 ml, p = 0.0003). The RAESV determined by 3D techniques was 111.9 +/- 29.1 ml. The LV size and LVM were greater in men than in women (p < 0.01). The LV size declined with age (p < 0.01), but LVM did not. This study establishes age- and gender-specific values for LV, RV, LA, and RA size, function, and mass in adults free of cardiovascular disease, hypertension, and obesity using 1D, 2D, and 3D methods. These data can be

  6. Control over Permissible Short Emergency Overloads in Power Transformers

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2010-01-01

    Full Text Available The paper proposes a method for determination a permissible duration of short intermittent overloads of power transformers that permits to avoid non-permissible over-heating of winding insulation and fully utilize overloading transformer ability.

  7. Overload blunts baroreflex only in overreached athletes.

    Science.gov (United States)

    Bourdillon, Nicolas; Yazdani, Sasan; Nilchian, Masih; Mariano, Alessio; Vesin, Jean-Marc; Millet, Grégoire P

    2018-01-31

    Heart rate variability (HRV) is commonly used to diagnose overreaching and monitor athletes' responses to training. Baroreflex sensitivity (BRS) is modified by changes in training load and might be another means to detect overreaching. The goal of this study was to assess BRS and HRV changes in two groups of athletes responding either negatively (FOR) or positively (AF) to similar training overload. Fifteen athletes performed 2-week baseline (BSL) training followed by 3-week overload (+45%; OVL) and 2-week recovery (-20%; RCV). HRV, training load and subjective fatigue were measured daily via questionnaires. BRS, salivary cortisol and testosterone, and submaximal exercise and maximal 3-km run performances were measured at the end of each period. Based on their performance change during OVL, 8 athletes were diagnosed as FOR and 7 as AF. Subjective fatigue was increased in FOR athletes during OVL. BRS increased in AF but not in FOR athletes during RCV. At the end of RCV, cortisol and testosterone were higher than BSL in both groups. Three weeks of similar training overload can induce either performance enhancement or overreaching. The changes in submaximal exercise and maximal performances and in subjective fatigue were the fastest-responding parameters that distinguished the two groups of athletes during OVL. Training overload blunted the increase in BRS in FOR only. Most of the differences in BRS were observed during the recovery period. BRS appears to be a more sensitive parameter than HRV for early monitoring of responses to training. Copyright © 2018. Published by Elsevier Ltd.

  8. Aggradation in rivers due to overloading

    NARCIS (Netherlands)

    Ribberink, J.S.; Van der Sande, J.T.M.

    1984-01-01

    The problem of aggradation in a river due to overloading is tackled with a mathematical model consisting of a set of one-dimensional (in space) basic equations in which the water motion is assumed to be quasi-steady and the sediment transport is determined by local conditions. Analytical solutions

  9. Tidal Volume Delivery and Endotracheal Tube Leak during Cardiopulmonary Resuscitation in Intubated Newborn Piglets with Hypoxic Cardiac Arrest Exposed to Different Modes of Ventilatory Support.

    Science.gov (United States)

    Mendler, Marc R; Weber, Claudia; Hassan, Mohammad A; Huang, Li; Mayer, Benjamin; Hummler, Helmut D

    2017-01-01

    There are few data available on the interaction of inflations, chest compressions (CC), and delivery of tidal volumes in newborn infants undergoing resuscitation in the presence of endotracheal tube (ET) leaks. To determine the effects of different respiratory support strategies along with CC on changes in tidal volume and ET leaks in hypoxic newborn piglets with cardiac arrest. Asphyxiated newborn piglets, intubated with weight-adapted uncuffed ET, were randomized into three groups and resuscitated according to ILCOR 2010 guidelines: (1) T-piece resuscitator (TPR) group = peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP) 25/5 cm H2O, rate 30/min, inflations interposed between CC (3:1 ratio); (2) self- inflating bag (SIB) group = PIP 25 cm H2O without PEEP, rate 30/min, inflations interposed between CC (3:1 ratio), and (3) ventilator group = PIP/PEEP of 25/5 cm H2O, rate 30/min. CC were applied with a rate of 120/min without synchrony to inflations. We observed a significant increase of leak (average increase 11.4%) when CC was added to respiratory support (p = 0.0001). Expired tidal volume was larger in the SIB group than in the two other modes which both applied PEEP. However, tidal volumes caused by CC only were larger in the two groups with PEEP than in the SIB group (without PEEP). There is interaction between lung inflations and CC affecting leak and delivery of tidal volume, which may be influenced by the mode/device used for respiratory support. Leak is larger in the presence of PEEP. However, CC cause additional tidal volume which is larger in the presence of PEEP. © 2016 S. Karger AG, Basel.

  10. Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress

    DEFF Research Database (Denmark)

    Brothers, R M; Pecini, Redi; Dalsgaard, M

    2014-01-01

    Volume loading normalizes tolerance to a simulated hemorrhagic challenge in heat-stressed individuals, relative to when these individuals are thermoneutral. The mechanism(s) by which this occurs is unknown. This project tested two unique hypotheses; that is, the elevation of central blood volume ...

  11. Goal-directed fluid restriction using stroke volume variation and cardiac index during one-lung ventilation: a randomized controlled trial.

    Science.gov (United States)

    Xu, Hui; Shu, Shu-Hua; Wang, Di; Chai, Xiao-Qing; Xie, Yan-Hu; Zhou, Wei-De

    2017-09-01

    Goal-directed therapy confers a strong prognosis in patients undergoing major cardiac or noncardiac surgery. The present study investigated whether intraoperative goal-directed fluid restriction (GDFR) using stroke volume variation (SVV) and cardiac index could improve oxygenation and postoperative outcome in patients undergoing one-lung ventilation (OLV). A Total of 168 patients scheduled for elective thoracoscopic lobectomy under OLV were randomized into the GDFR protocol (group G) or conventional fluid therapy groups (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP), central venous pressure (CVP), and urine volume, whereas those in group G received GDFR protocol associated with the SVV from 10-13% and the cardiac index was controlled at a minimum of 2.5 L/min/m2. The primary outcome variable was PaO2/FiO2. The secondary outcomes were other pulmonary variables and lung mechanics, inflammatory response, the incidence of postoperative pulmonary complications, and the length of hospital stay. During surgery, the PaO2/FiO2 ratio in group G was more than that of group C at 30 and 60 min after OLV, 10 min after re-expansion, and the end of the operation (259±29 vs. 314±34; 253±30 vs. 308±35; 341±34 vs. 394±39; 349±35 vs. 401±39, respectively, all Pmechanics with the initiation of OLV. The incidence of postoperative pulmonary complications such as acute lung injury and pneumonia, and the length of hospital stay were decreased by GDFR protocol as compared to conventional fluid therapy (all P<0.05). However, there were no significant differences between groups with respect to the concentration of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). The GDFR protocol based on SVV and cardiac index applied in patients undergoing OLV improves intraoperative pulmonary oxygenation. It can also reduce the postoperative complications and length of hospital stay. However, the

  12. Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress

    DEFF Research Database (Denmark)

    Brothers, R M; Pecini, Redi; Dalsgaard, Morten

    2014-01-01

    conditions prior to and during a simulated hemorrhagic challenge. Heat stress did not change indices of diastolic function. Subsequent volume infusion elevated indices of diastolic function, specifically early diastolic mitral annular tissue velocity (E') and early diastolic propagation velocity (E) relative......Volume loading normalizes tolerance to a simulated hemorrhagic challenge in heat-stressed individuals, relative to when these individuals are thermoneutral. The mechanism(s) by which this occurs is unknown. This project tested two unique hypotheses; that is, the elevation of central blood volume...... via volume loading while heat stressed would 1) increase indices of left ventricular diastolic function, and 2) preserve left ventricular end-diastolic volume (LVEDV) during a subsequent simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Indices of left ventricular...

  13. Iron excretion in iron dextran-overloaded mice.

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-10-01

    Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (piron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion.

  14. Iron excretion in iron dextran-overloaded mice

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-01-01

    Background Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Materials and methods Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. Results In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. Conclusions This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion. PMID:24960657

  15. Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

    Science.gov (United States)

    Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

    1987-01-01

    The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

  16. Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure.

    Science.gov (United States)

    Maier, Joscha; Sawall, Stefan; Kachelrieß, Marc

    2014-05-01

    Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the

  17. Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

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    Maier, Joscha, E-mail: joscha.maier@dkfz.de [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Sawall, Stefan; Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany and Institute of Medical Physics, University of Erlangen–Nürnberg, 91052 Erlangen (Germany)

    2014-05-15

    Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the

  18. Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions.

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    Kiliç, Zübeyir; Uçar, Birsen; Özdemir, Gökmen; Colak, Ömer; Bal, Cengiz; Ertuğrul, Türkan

    2014-09-01

    The pathological effects of matrix metalloproteinases and their tissue inhibitors in cardiovascular diseases are of considerable interest. In our study, we aimed to determine and evaluate the potential significance of circulating matrix metalloproteinases-2 and 9, tissue inhibitors of matrix metalloproteinases-1 and 2 levels in four patient subgroup of pediatric cardiology field and expose pathophysiologic differences between these groups. Eighty-seven patients with the diagnosis of congenital heart disease and 47 healthy controls were enrolled in the study. The study group was stratified to 4 subgroups; 14 patients with right ventricular volume overload, 30 patients with left ventricular volume overload, 19 patients with left to right shunt who developed pulmonary hypertension and 24 patients with cyanotic congenital heart disease. For evaluation of the relationships between serum matrix metalloproteinases and their tissue inhibitors levels with cardiac structures and functions; complete blood count, arterial oxygen saturation, detailed echocardiographic measurements (including tissue Doppler) in all patients and hemodynamic parameters of the patients who went to cardiac catheterization were recorded. Serum matrix metalloproteinase levels were determined by ELISA test. Statistical evaluations were performed with SPSS 16.0. For parameters showing normal distribution, comparisons were made with t-test and ANOVA test. However, for parameters without normal distribution, groups were compared with Mann-Whitney U test and Kruskal-Wallis test. We demonstrated that serum tissue inhibitors of matrix metalloproteinases-1 levels of patients with pulmonary hypertension secondary to congenital heart diseases were significantly higher than the patients with left to right shunt without pulmonary hypertension and controls (p<0.01). Although serum matrix metalloproteinases and their tissue inhibitors levels in patients with cyanotic congenital heart diseases and patients with

  19. DJ-1 activates autophagy in the repression of cardiac hypertrophy.

    Science.gov (United States)

    Xue, Ruicong; Jiang, Jingzhou; Dong, Bin; Tan, Weiping; Sun, Yu; Zhao, Jingjing; Chen, Yili; Dong, Yugang; Liu, Chen

    2017-11-01

    Cardiac hypertrophy is the risk factor of heart failure when the heart is confronted with pressure overload or neurohumoral stimuli. Autophagy, a conserved degradative pathway, is one of the important mechanisms involved in the regulation of cardiac hypertrophy. DJ-1 is a traditional anti-oxidative protein and emerging evidence suggested that DJ-1 might modulate autophagy. However, the regulation of autophagy by DJ-1 in the process of cardiac hypertrophy remains unknown. In our study, we firstly discovered that the expression of DJ-1declined in the process of pressure overload cardiac hypertrophy, and its alteration was parallel with the impairment of autophagy. Furthermore, we proved that DJ-1 knockout mice exhibited a more hypertrophied phenotype than wildtype mice in cardiac hypertrophy which indicated that DJ-1 is responsible for the repression of cardiac hypertrophy. Furthermore, DJ-1 knockout significantly exacerbated pulmonary edema due to cardiac hypertrophy. In the process of cardiac hypertrophy, DJ-1 knockout significantly impaired autophagy activation and enhanced mTORC1 and mTORC2 phosphorylation were found. Similarly, our in vitro study proved that DJ-1 overexpression ameliorated phenylephrine (PE)-induced cardiac hypertrophy and promoted autophagy activation. Taken together, DJ-1 might repress both pressure overload and PE-induced cardiac hypertrophy via the activation of autophagy. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Assessment of Iron Overload in Homozygous and Heterozygous Beta Thalassemic Children below 5 Years of Age

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    Dhiraj J. Trivedi

    2014-07-01

    Full Text Available Background: Thalassemia is a genetic disease having 3-7% carrier rate in Indians. It is transfusion dependent anemia having high risk of iron overloading. A clinical symptom of iron overload becomes detectable in second decade causing progressive liver, heart and endocrine glands damage. There is a need to assess iron overload in thalassemics below 5 years of age to protect them from complications at later age of life. Aims and objectives: Present study was undertaken to estimate serum iron status and evaluate serum transferrin saturation in both homozygous & heterozygous form of thalassemia as an index of iron overload among children of one to five years of age. Materials and Methods: Clinically diagnosed thirty cases of β thalassemia major & thirty cases of β thalassemia minor having severe anemia, hepatospleenomegaly and between 1 year to 5 years of age were included in study group and same age matched healthy controls were included in the study. RBC indices and HbA, HbA2 and HbF were estimated along with serum iron & serum Total Iron Binding Capacity (TIBC and serum transferrin levels. Results: Significant difference was observed in hemoglobin levels between control and both beta thalassemia groups. Mean Corpuscular Volume (MCV and Mean Corpuscular Hemoglobin (MCH values were reduced. Hemoglobin electrophoresis showed the elevated levels of HbF and HbA2 in both beta thalassemia groups. Among serum iron parameters, serum iron, TIBC and transferrin saturation were elevated whereas serum transferrin levels were low in thalassemia major in children below 5 years of age. Conclusion: Although clinical symptoms of iron overload have been absent in thalassemic children below five years of age, biochemical iron overloading has started at much lower age which is of great concern.

  1. Effects of acute plasma volume expansion on renal perfusion, filtration, and oxygenation after cardiac surgery: a randomized study on crystalloid vs colloid.

    Science.gov (United States)

    Skytte Larsson, J; Bragadottir, G; Krumbholz, V; Redfors, B; Sellgren, J; Ricksten, S E

    2015-11-01

    In the present randomized study, we evaluated the differential effects of a colloid and a crystalloid fluid on renal oxygen delivery (RD(O2)), glomerular filtration (GFR), renal oxygen consumption ((RV(O2))), and the renal oxygen supply-demand relationship (i.e., renal oxygenation) after cardiac surgery with cardiopulmonary bypass. Thirty patients with normal preoperative renal function, undergoing uncomplicated cardiac surgery, were studied in the intensive care unit in the early postoperative period. Patients were randomized to receive a bolus dose of either a crystalloid (Ringers-acetate 20 ml kg(-1), n=15) or a colloid solution (Venofundin) 10 ml kg(-1), n=15). Systemic haemodynamics were measured via a pulmonary artery catheter. Renal blood flow and GFR were measured by the renal vein retrograde thermodilution technique and by renal extraction of 51Cr-EDTA (=filtration fraction). Arterial and renal vein blood samples were obtained for measurements of renal oxygen delivery (RD(O2)) and RV(O2). Renal oxygenation was estimated from the renal oxygen extraction. Despite an increase in cardiac index and renal blood flow with both fluids, neither of the fluids improved RD(O2), because they both induced haemodilution. The GFR increased in the crystalloid (28%) but not in the colloid group. The crystalloid increased the filtration fraction (24%) and renal oxygen extraction (23%), indicating that the increase in GFR, the major determinant of RV(O2), was not matched by a proportional increase in RD(O2). Neither the colloid nor the crystalloid improved RD(O2) when used for postoperative plasma volume expansion. The crystalloid-induced increase in GFR was associated with impaired renal oxygenation, which was not seen with the colloid. NCT01729364. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Prevalence and risk factors of fluid overload in Southern Chinese continuous ambulatory peritoneal dialysis patients.

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    Qunying Guo

    Full Text Available BACKGROUND: Fluid overload is frequently present in CAPD patients and one of important predictors of mortality. The aim of this study is to investigate the prevalence and associated risk factors in a cohort study of Southern Chinese CAPD patients. METHODS: The patients (receiving CAPD 3 months and more in our center were investigated from January 1, 2008 to December 31, 2009. Multi-frequency bioelectrical impedance analysis was used to assess the patient's body composition and fluid status. RESULTS: A total of 307 CAPD patients (43% male, mean age 47.8±15.3 years were enrolled, with a median duration of PD 14.6 (5.9-30.9 months. Fluid overload (defined by Extracellular water/Total body water (ECW/TBW≥0.40 was present in 205 (66.8% patients. Univariate analysis indicated that ECW/TBW were inversely associated with body mass index (r = -0.11, P = 0.047, subjective global assessment score (r = -0.11, P = 0.004, body fat mass (r = -0.15, P = 0.05, serum albumin (r = -0.32, P<0.001, creatinine (r = -0.14, P = 0.02, potassium (r = -0.15, P = 0.02, and residual urine output (r = -0.14, P = 0.01, positively associated with age (r = 0.27, P<0.001, Chalrlson Comorbidity Index score (r = 0.29, P<0.001, and systolic blood pressure (r = 0.22, P<0.001. Multivariate linear regression showed that lower serum albumin (β = -0.223, P<0.001, lower body fat mass (β = -0.166, P = 0.033, old age (β = 0.268, P<0.001, higher systolic blood pressure (β = 0.16, P = 0.006, less residual urine output (β = -0.116, P = 0.042, and lower serum potassium (β = -0.126, P = 0.03 were independently associated with higher ECW/TBW. After 1 year of follow-up, the cardiac event rate was significantly higher in the patients with fluid overload (17.1% vs 6.9%, P = 0.023 than that of the normal hydrated patients. CONCLUSIONS: The prevalence of fluid overload was high in CAPD patients. Fluid overload in CAPD patients were independently associated with protein-energy wasting, old

  3. Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume Cardiac Surgical Intensive Care Unit

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    Manoj Kumar Sahu

    2016-01-01

    Full Text Available Background: Nosocomial infections (NIs in the postoperative period not only increase morbidity and mortality, but also impose a significant economic burden on the health care infrastructure. This retrospective study was undertaken to (a evaluate the incidence, characteristics, risk factors and outcomes of NIs and (b identify common microorganisms responsible for infection and their antibiotic resistance profile in our Cardiac Surgical Intensive Care Unit (CSICU. Patients and Methods: After ethics committee approval, the CSICU records of all patients who underwent cardiovascular surgery between January 2013 and December 2014 were reviewed retrospectively. The incidence of NI, distribution of NI sites, types of microorganisms and their antibiotic resistance, length of CSICU stay, and patient-outcome were determined. Results: Three hundred and nineteen of 6864 patients (4.6% developed NI after cardiac surgery. Lower respiratory tract infections (LRTIs accounted for most of the infections (44.2% followed by surgical-site infection (SSI, 11.6%, bloodstream infection (BSI, 7.5%, urinary tract infection (UTI, 6.9% and infections from combined sources (29.8%. Acinetobacter, Klebsiella, Escherichia coli, and Staphylococcus were the most frequent pathogens isolated in patients with LRTI, BSI, UTI, and SSI, respectively. The Gram-negative bacteria isolated from different sources were found to be highly resistant to commonly used antibiotics. Conclusion: The incidence of NI and sepsis-related mortality, in our CSICU, was 4.6% and 1.9%, respectively. Lower respiratory tract was the most common site of infection and Gram-negative bacilli, the most common pathogens after cardiac surgery. Antibiotic resistance was maximum with Acinetobacter spp.

  4. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

    Science.gov (United States)

    Abel, E. Dale; Doenst, Torsten

    2011-01-01

    Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

  5. Três protocolos fisioterapêuticos: efeitos sobre os volumes pulmonares após cirurgia cardíaca Three physiotherapy protocols: effects on pulmonary volumes after cardiac surgery

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    Cristina Márcia Dias

    2011-02-01

    Full Text Available OBJETIVO: Avaliar o volume inspiratório e os efeitos da espirometria de incentivo (EI e da técnica breath stacking (BS sobre a CVF em pacientes submetidos a cirurgia cardíaca. MÉTODOS: Estudo prospectivo controlado e randomizado com 35 pacientes submetidos a cirurgia cardíaca no Hospital de Força Aérea do Galeão, Rio de Janeiro (RJ. Todos os pacientes realizaram procedimentos de mobilização e tosse e foram randomicamente alocados em três grupos: grupo exercício controle (EC, que realizou somente esses procedimentos; grupo EI, que realizou inspirações profundas utilizando um espirômetro de incentivo; e grupo BS, que realizou esforços inspiratórios sucessivos utilizando uma máscara facial acoplada a uma válvula unidirecional. A espirometria forçada foi realizada no período pré-operatório e do primeiro ao quinto dia de pós-operatório. O volume inspiratório foi medido durante as manobras nos grupos EI e BS. RESULTADOS: No primeiro dia de pós-operatório, a CVF diminuiu significativamente em todos os grupos (EC: 87,1 vs. 32,0%; EI: 75,3 vs. 29,5%; e BS: 81,9 vs. 33,2%; p OBJECTIVE: To evaluate inspiratory volume in patients undergoing cardiac surgery and to determine the effects that incentive spirometry (IS and the breath stacking (BS technique have on the recovery of FVC in such patients. METHODS: A prospective, controlled, randomized clinical trial involving 35 patients undergoing cardiac surgery at the Hospital de Força Aérea do Galeão (HFAG, Galeão Air Force Hospital, in the city of Rio de Janeiro, Brazil. The patients, all of whom performed mobilization and cough procedures, were randomly divided into three groups: exercise control (EC, performing only the abovementioned procedures; IS, performing the abovementioned procedures and instructed to take long breaths using an incentive spirometer; and BS, performing the abovementioned procedures, together with successive inspiratory efforts using a facial mask coupled

  6. Cardiothoracic ratio on chest radiograph in pediatric heart disease: How does it correlate with heart volumes at magnetic resonance imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Grotenhuis, Heynric B. [The University of Toronto, Division of Cardiology, Department of Paediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto (Canada); Zhou, Cheng; Isaac, Kathryn V. [The University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto (Canada); Tomlinson, George [University of Toronto, Department of Medicine, Toronto General Hospital and Mt. Sinai Hospital, Toronto (Canada); Seed, Mike; Grosse-Wortmann, Lars; Yoo, Shi-Joon [The University of Toronto, Division of Cardiology, Department of Paediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto (Canada); The University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto (Canada)

    2015-10-15

    The cardiothoracic ratio by chest radiograph is widely used as a marker of cardiac size. The purpose of this study is to correlate cardiothoracic ratio and cardiac volumes as measured by cardiovascular magnetic resonance (MR) in common structural and myopathic heart disease with increased cardiac size due to volume overload or hypertrophy. A retrospective single center study was performed in all patients between 2007 and 2013 with repaired tetralogy of Fallot (TOF), aortic regurgitation, isolated left-to-right shunt and hypertrophic cardiomyopathy (HCM) who underwent cardiovascular MR and chest radiograph within 6 months of each other. Cardiothoracic ratios by chest radiograph (frontal and lateral) were compared to cardiac volumes (indexed for body surface area) by cardiovascular MR. One hundred twenty-seven patients (mean age: 11.2 ± 5.5 years) were included in this study (76 with TOF, 23 with isolated left-to-right shunt, 16 with aortic regurgitation and 12 with HCM). Frontal cardiothoracic ratio of all groups correlated with indexed right ventricular (RV) end-diastolic volume (EDVI) (r = 0.40, P < 0.01) and indexed total heart volume (THVI) (r = 0.27, P < 0.01). In TOF patients, frontal cardiothoracic ratio correlated with RVEDVI (r = 0.34, P < 0.01; coefficient of variation = 27.6%), indexed RV end-systolic volume (ESVI) (r = 0.44, P < 0.01; coefficient of variation = 33.3%) and THVI (r = 0.35, P < 0.01; coefficient of variation = 19.6%), although RV volumes and THVI showed widespread variation given the high coefficients of variation. In patients with aortic regurgitation, frontal cardiothoracic ratio correlated with left ventricular (LV) EDVI (r = 0.50, P = 0.047), but not with THVI and aortic regurgitant fraction, and widespread variation for LV EDVI (coefficient of variation = 19.2%), LV ESVI (coefficient of variation = 32.5%) and THVI (coefficient of variation = 13.6%) was also observed. Frontal cardiothoracic ratio was not correlated with cardiac volumes

  7. CQ Switch Analysis under Traffic Overload

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    I. Maljević

    2011-06-01

    Full Text Available An analysis of 2x2 crossbar packet switch with buffers at crosspoints and round robin scheduling algorithm is presented in this paper. The analysis is performed for a non-admissible traffic pattern, where output ports are overloaded. The case of full offered load is observed and output ports are loaded with packets that have different arrival probabilities. In addition to the parameters that are commonly observed in such an analysis (throughput and average packet delay, memory requirements for the implementation of the buffer, as well as fair representation when servicing the buffer - the so-called fairness are also analyzed. The results show that even for a switch with a small number of ports very large buffers should be implemented, if we want to achieve satisfactory performance under traffic overload.

  8. Management of iron overload in hemoglobinopathies: what is the appropriate target iron level?

    Science.gov (United States)

    Coates, Thomas D; Carson, Susan; Wood, John C; Berdoukas, Vasilios

    2016-03-01

    Patients with thalassemia become iron overloaded from increased absorption of iron, ineffective erythropoiesis, and chronic transfusion. Before effective iron chelation became available, thalassemia major patients died of iron-related cardiac failure in the second decade of life. Initial treatment goals for chelation therapy were aimed at levels of ferritin and liver iron concentrations associated with prevention of adverse cardiac outcomes and avoidance of chelator toxicity. Cardiac deaths were greatly reduced and survival was much longer. Epidemiological data from the general population draw clear associations between increased transferrin saturation (and, by inference, labile iron) and early death, diabetes, and malignant transformation. The rate of cancers now seems to be significantly higher in thalassemia than in the general population. Reduction in iron can reverse many of these complications and reduce the risk of malignancy. As toxicity can result from prolonged exposure to even low levels of excess iron, and survival in thalassemia patients is now many decades, it would seem prudent to refocus attention on prevention of long-term complications of iron overload and to maintain labile iron and total body iron levels within a normal range, if expertise and resources are available to avoid complications of overtreatment. © 2016 New York Academy of Sciences.

  9. Noninvasive assessment of filling pressure and left atrial pressure overload in severe aortic valve stenosis: relation to ventricular remodeling and clinical outcome after aortic valve replacement

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbæk, Lars; Poulsen, Mikael K

    2011-01-01

    One of the hemodynamic consequences of aortic valve stenosis is pressure overload leading to left atrial dilatation. Left atrial size is a known risk factor providing prognostic information in several cardiac conditions. It is not known if this is also the case in patients with aortic valve...

  10. The relation between total epicardial fat volume assessed by cardiac CT and the presence of atrial fibrillation

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    Mohamed Abdelshafy Tabl

    2016-06-01

    Conclusion: Epicardial fat is associated with the presence of AF and predicts chronicity. These associations are independent to systemic measures of adiposity and sensitive echocardiographic parameters as LA volume index. These findings are consistent with the hypothesis of a local pathogenic effect of epicardial fat on the arrhythmogenic substrate supporting AF.

  11. Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.

    Science.gov (United States)

    Kodati, Devender; Yellu, Narsimhareddy

    2017-06-01

    Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  12. Exercise training in adverse cardiac remodeling.

    Science.gov (United States)

    Duncker, Dirk J; van Deel, Elza D; de Waard, Monique C; de Boer, Martine; Merkus, Daphne; van der Velden, Jolanda

    2014-06-01

    Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction. Here we present studies from our laboratory into the effects of exercise training on pathological cardiac remodeling and dysfunction in mice. The results indicate that even in the presence of a large infarct, exercise training exerts beneficial effects on the heart. These effects were mimicked in part by endothelial nitric oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency, demonstrating the importance of nitric oxide signaling in mediating the cardiac effects of exercise. Exercise prior to a myocardial infarction was also cardioprotective. In contrast, exercise tended to aggravate pathological cardiac remodeling and dysfunction in the setting of pressure-overload produced by an aortic stenosis. These observations emphasize the critical importance of the underlying pathological stimulus for cardiac hypertrophy and remodeling, in determining the effects of exercise training. Future studies are needed to define the influence of exercise type, intensity and duration in different models and severities of pathological cardiac remodeling. Together such studies will aid in optimizing the therapy of exercise training in the setting of cardiovascular disease.

  13. Automatic quantification of aortic regurgitation using 3D full volume color doppler echocardiography: a validation study with cardiac magnetic resonance imaging.

    Science.gov (United States)

    Choi, Jaehuk; Hong, Geu-Ru; Kim, Minji; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Mancina, Joel; Ha, Jong-Won; Chung, Namsik

    2015-10-01

    Recent advances in real-time three-dimensional (3D) echocardiography provide the automated measurement of mitral inflow and aortic stroke volume without the need to assume the geometry of the heart. The aim of this study is to explore the ability of 3D full volume color Doppler echocardiography (FVCDE) to quantify aortic regurgitation (AR). Thirty-two patients with more than a moderate degree of AR were enrolled. AR volume was measured by (1) two-dimensional-CDE, using the proximal isovelocity surface area (PISA) and (2) real-time 3D-FVCDE with (3) phase-contrast cardiac magnetic resonance imaging (PC-CMR) as the reference method. Automated AR quantification using 3D-FVCDE was feasible in 30 of the 32 patients. 2D-PISA underestimated the AR volume compared to 3D-FVCDE and PC-CMR (38.6 ± 9.9 mL by 2D-PISA; 49.5 ± 10.2 mL by 3D-FVCDE; 52.3 ± 12.6 mL by PC-CMR). The AR volume assessed by 3D-FVCDE showed better correlation and agreement with PC-CMR (r = 0.93, p PISA (r = 0.76, p PISA (k = 0.53). In patients with eccentric jets, only 30% were correctly graded by 2D-PISA. Conversely, almost all patients with eccentric jets (86.7%) were correctly graded by 3D-FVCDE. In patients with multiple jets, only 3 out of 10 were correctly graded by 2D-PISA, while 3D-FVCDE correctly graded 9 out of 10 of these patients. Automated quantification of AR using the 3D-FVCDE method is clinically feasible and more accurate than the current 2D-based method. AR quantification by 2D-PISA significantly misclassified AR grade in patients with eccentric or multiple jets. This study demonstrates that 3D-FVCDE is a valuable tool to accurately measure AR volume regardless of AR characteristics.

  14. Pre-hospital cooling of patients following cardiac arrest is effective using even low volumes of cold saline.

    Science.gov (United States)

    Skulec, Roman; Truhlár, Anatolij; Seblová, Jana; Dostál, Pavel; Cerný, Vladimír

    2010-01-01

    Pre-hospital induction of therapeutic mild hypothermia (TH) may reduce post-cardiac arrest brain injury in patients resuscitated from out-of-hospital cardiac arrest. Most often, it is induced by a rapid intravenous administration of as much as 30 ml/kg of cold crystalloids. We decided to assess the pre-hospital cooling effectivity of this approach by using a target dose of 15-20 ml/kg of 4°C cold normal saline in the setting of the physician-staffed Emergency Medical Service. The safety and impact on the clinical outcome have also been analyzed. We performed a prospective observational study with a retrospective control group. A total of 40 patients were cooled by an intravenous administration of 15-20 ml/kg of 4°C cold normal saline during transport to the hospital (TH group). The pre-hospital decrease of tympanic temperature (TT) was analyzed as the primary endpoint. Patients in the control group did not undergo any pre-hospital cooling. In the TH group, administration of 12.6 ± 6.4 ml/kg of 4°C cold normal saline was followed by a pre-hospital decrease of TT of 1.4 ± 0.8°C in 42.8 ± 19.6 min (p cold saline. In the TH group, a trend toward a reduced need for catecholamines during transport was detected (35.0 vs. 52.5%, p = 0.115). There were no differences in demographic variables, comorbidities, parameters of the cardiopulmonary resuscitation and in other post-resuscitation characteristics. The coupling of pre-hospital cooling with subsequent in-hospital TH predicted a favorable neurological outcome at hospital discharge (OR 4.1, CI95% 1.1-18.2, p = 0.046). Pre-hospital induction of TH by the rapid intravenous administration of cold normal saline has been shown to be efficient even with a lower dose of coolant than reported in previous studies. This dose can be associated with a favorable impact on circulatory stability early after the return of spontaneous circulation and, when coupled with in-hospital continuation of cooling, can potentially improve the

  15. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

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    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  16. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

    DEFF Research Database (Denmark)

    Patrick, David M; Montgomery, Rusty L; Qi, Xiaoxia

    2010-01-01

    cardiac hypertrophy and fibrosis in rodents in response to pressure overload. In contrast, we have shown here that miR-21-null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac......MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3' untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent...... for pathological cardiac remodeling....

  17. The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and macrophages is mediated by the IFNγ-CXCL10-CXCR3 axis.

    Science.gov (United States)

    Koren, L; Barash, U; Zohar, Y; Karin, N; Aronheim, A

    2017-02-01

    Pressure overload induces adaptive and maladaptive cardiac remodeling processes in the heart. Part of the maladaptive process is the cross-talk between cardiomyocytes and macrophages which is dependent on the function of the Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in cardiomyocytes-macrophages communication leading to macrophages recruitment to the heart and cardiac maladaptive remodeling is currently unknown. Isolated peritoneal macrophages from either wild type or ATF3-KO mice were cultured in serum free medium to collect conditioned medium (CM). CM was used to probe an antibody cytokine/chemokine array. The interferon γ induced protein 10kDa, CXCL10, was found to be enriched in wild type macrophages CM. Wild type cardiomyocytes treated with CXCL10 in vitro, resulted in significant increase in cell volume as compared to ATF3-KO cardiomyocytes. In vivo, pressure overload was induced by phenylephrine (PE) infusion using micro-osmotic pumps. Consistently, CXCL11 (CXCL10 competitive agonist) and CXCL10 receptor antagonist (AMG487) attenuated PE-dependent maladaptive cardiac remodeling. Significantly, we show that the expression of the CXCL10 receptor, CXCR3, is suppressed in cardiomyocytes and macrophages derived from ATF3-KO mice. CXCR3 is positively regulated by ATF3 through an ATF3 transcription response element found in its proximal promoter. Finally, mice lacking CXCR3 display a significant reduction of cardiac remodeling processes following PE infusion. Chronic PE infusion results in a unique cardiomyocytes-macrophages cross-talk that is mediated by IFNγ. Subsequently, macrophages that are recruited to the heart secrete CXCL10 resulting in maladaptive cardiac remodeling mediated by the CXCR3 receptor. ATF3-KO mice escape from PE-dependent maladaptive cardiac remodeling by suppressing the IFNγ-CXCL10-CXCR3 axis at multiple levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Design of vehicle overload detection system based on geophone

    Science.gov (United States)

    Hu, Siquan; Kong, Min; She, Chundong

    2017-08-01

    A vehicle overload detection system is proposed based on geophone. Under normal circumstances, when overloaded vehicles and ordinary vehicles pass through the road, the amplitude of the ground vibration will be different, and the geophone sensor can detect tiny vibrations of the ground. The system includes information acquisition module, signal conditioning module and wireless transmission module. The collected vibration data is transmitted through the wireless transmission module to the background, and the SVM algorithm is used to classify the information and determine whether the vehicle is overloaded. Experiments show that the system can detect overload accurately.

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

    Science.gov (United States)

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

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P cardiac functions and ameliorate cardiac structures in rats with chronic heart failure probably through dilating the blood vessels and affecting the extracellular collagen metabolism.

  20. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    Science.gov (United States)

    Zhang, Ying; Wang, Hao; Cui, Lijing; Zhang, Yuanyuan; Liu, Yang; Chu, Xi; Liu, Zhenyi; Zhang, Jianping; Chu, Li

    2015-01-01

    Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen), a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old) were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp) quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and protein expression levels of type I collagen (COL I), type I collagen (COL III), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative stress.

  1. [Chronic nicotinamide overload and type 2 diabetes].

    Science.gov (United States)

    Zhou, Shi-Sheng; Li, Da; Zhou, Yi-Ming; Sun, Wu-Ping; Liu, Xing-Xing; Lun, Yong-Zhi

    2010-02-25

    Type 2 diabetes is a major global health problem. It is generally accepted that type 2 diabetes is the result of gene-environmental interaction. However, the mechanism underlying the interaction is unclear. Diet change is known to play an important role in type 2 diabetes. The fact that the global high prevalence of type 2 diabetes has occurred following the spread of food fortification worldwide suggests a possible involvement of excess niacin intake. Our recent study found that nicotinamide overload and low nicotinamide detoxification may induce oxidative stress associated with insulin resistance. Based on the relevant facts, this review briefly summarized the relationship between the prevalence of type 2 diabetes and the nicotinamide metabolism changes induced by excess niacin intake, aldehyde oxidase inhibitors, liver diseases and functional defects of skin. We speculate that the gene-environmental interaction in type 2 diabetes may be a reflection of the outcome of the association of chronic nicotinamide overload-induced toxicity and the relatively low detoxification/excretion capacity of the body. Reducing the content of niacin in foods may be a promising strategy for the control of type 2 diabetes.

  2. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

    Full Text Available Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulates health and lifespan.

  3. Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study

    OpenAIRE

    Salahuddin, Nawal; Sammani, Mustafa; Hamdan, Ammar; Joseph, Mini; Al-Nemary, Yasir; Alquaiz, Rawan; Dahli, Ranim; Maghrabi, Khalid

    2017-01-01

    Background Acute Kidney injury (AKI) is common and increases mortality in the intensive care unit (ICU). We carried out this study to explore whether fluid overload is an independent risk factor for AKI. Methods Single-center prospective, observational study. Consecutively admitted, ICU patients were followed for development of AKI. Intravenous fluid volumes, daily fluid balances were measured, hourly urine volumes, daily creatinine levels were recorded. Results Three hundred thirty nine pati...

  4. Iron overload and apoptosis of HL-1 cardiomyocytes: effects of calcium channel blockade.

    Directory of Open Access Journals (Sweden)

    Mei-pian Chen

    Full Text Available Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC and T-type calcium channels (TTCC have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II and Fe(III ingress in cultured cardiomyocytes and ensuing apoptosis.Fe(II and Fe(III uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC.Iron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis.Our study implicates LTCC as major mediators of Fe(III uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in

  5. Automatic intensity-based 3D-to-2D registration of CT volume and dual-energy digital radiography for the detection of cardiac calcification

    Science.gov (United States)

    Chen, Xiang; Gilkeson, Robert; Fei, Baowei

    2007-03-01

    We are investigating three-dimensional (3D) to two-dimensional (2D) registration methods for computed tomography (CT) and dual-energy digital radiography (DR) for the detection of coronary artery calcification. CT is an established tool for the diagnosis of coronary artery diseases (CADs). Dual-energy digital radiography could be a cost-effective alternative for screening coronary artery calcification. In order to utilize CT as the "gold standard" to evaluate the ability of DR images for the detection and localization of calcium, we developed an automatic intensity-based 3D-to-2D registration method for 3D CT volumes and 2D DR images. To generate digital rendering radiographs (DRR) from the CT volumes, we developed three projection methods, i.e. Gaussian-weighted projection, threshold-based projection, and average-based projection. We tested normalized cross correlation (NCC) and normalized mutual information (NMI) as similarity measurement. We used the Downhill Simplex method as the search strategy. Simulated projection images from CT were fused with the corresponding DR images to evaluate the localization of cardiac calcification. The registration method was evaluated by digital phantoms, physical phantoms, and clinical data sets. The results from the digital phantoms show that the success rate is 100% with mean errors of less 0.8 mm and 0.2 degree for both NCC and NMI. The registration accuracy of the physical phantoms is 0.34 +/- 0.27 mm. Color overlay and 3D visualization of the clinical data show that the two images are registered well. This is consistent with the improvement of the NMI values from 0.20 +/- 0.03 to 0.25 +/- 0.03 after registration. The automatic 3D-to-2D registration method is accurate and robust and may provide a useful tool to evaluate the dual-energy DR images for the detection of coronary artery calcification.

  6. review article: Phospholemman: A Novel Cardiac Stress Protein

    Science.gov (United States)

    Cheung, Joseph Y.; Zhang, Xue‐Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E.; Chan, Tung O.; Wang, JuFang

    2010-01-01

    Abstract Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co‐localizes and co‐immunoprecipitates with Na+‐K+‐ATPase, Na+/Ca2+ exchanger, and L‐type Ca2+ channel. Functionally, when phosphorylated at serine68, PLM stimulates Na+‐K+‐ATPase but inhibits Na+/Ca2+ exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L‐type Ca2+ channel. Therefore, PLM occupies a key modulatory role in intracellular Na+ and Ca2+ homeostasis and is intimately involved in regulation of excitation–contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na+ overload and simultaneously preserves inotropy by inhibiting Na+/Ca2+ exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na+‐K+‐ATPase, Na+/Ca2+ exchanger, and potentially L‐type Ca2+ channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189–196 PMID:20718822

  7. measurements of iron status and survival in african iron overload

    African Journals Online (AJOL)

    Introduction. Dietary iron overload is common in southern. Africa and there is a misconception that the condition is benign. 'Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. Methods. The study ...

  8. Cardiac T1 mapping in congenital heart disease: bolus vs. infusion protocols for measurements of myocardial extracellular volume fraction.

    Science.gov (United States)

    Al-Wakeel-Marquard, Nadya; Rastin, Sanaz; Muench, Frédéric; O H-Ici, Darach; Yilmaz, Sevim; Berger, Felix; Kuehne, Titus; Messroghli, Daniel R

    2017-12-01

    Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD). Healthy controls (n = 17; median age 24.0 years) and patients with CHD (n = 19; 25.0 years) were prospectively enrolled. Using modified Look-Locker inversion recovery T1 mapping before, 15 min after bolus injection, and during constant infusion of gadolinium-DOTA, T1 values were obtained for blood pool and myocardium of the left ventricle (LV), the interventricular septum (IVS), and the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation. ECV of LV, IVS and RV by bolus-only and bolus-infusion correlated significantly in CHD patients (r = 0.94, 0.95, and 0.74; p < 0.01, respectively) and healthy controls (r = 0.96, 0.89, and 0.64; p < 0.05, respectively). Bland-Altman plots revealed no significant bias between the techniques for any of the analyzed regions. ECV of LV and RV myocardium measured by bolus-only T1 mapping agrees well with bolus-infusion measurements in patients with CHD. The use of a bolus-only approach facilitates the integration of ECV measurements into existing CMR imaging protocols, allowing for assessment of diffuse myocardial fibrosis in CHD in clinical routine.

  9. Coronary Artery Remodeling in a Model of Left Ventricular Pressure Overload Is Influenced by Platelets and Inflammatory Cells

    Science.gov (United States)

    Yang, Fanmuyi; Dong, Anping; Mueller, Paul; Caicedo, Jessica; Sutton, Alyssa Moore; Odetunde, Juliana; Barrick, Cordelia J.; Klyachkin, Yuri M.; Abdel-Latif, Ahmed; Smyth, Susan S.

    2012-01-01

    Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes' accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1−/− mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation. PMID:22916095

  10. Extracorporeal life support after cardiac surgery in children: outcomes from a single institution.

    Science.gov (United States)

    Sasaki, Takashi; Asou, Toshihide; Takeda, Yuko; Onakatomi, Yasuko; Tominaga, Takashi; Yamamoto, Yusuke

    2014-01-01

    Extracorporeal life support (ECLS) is used after congenital heart surgery for several indications, including failure to separate from cardiopulmonary bypass, postoperative low cardiac output syndrome, and extracorporeal cardiopulmonary resuscitation. Here, we assessed the outcomes of ECLS in children after cardiac surgery at our institution. Medical records of all children who required postoperative ECLS at our institution were reviewed. Between 2003 and 2011, 36 (1.4%) of 2541 pediatric cardiac surgical cases required postoperative ECLS. Median age of patients was 64 days (range: 0 days-4.1 years). ECLS was in the form of either extracorporeal membrane oxygenation (ECMO; n = 24) or ventricular assist system (VAS; n = 12). Mean duration of ECLS was 4.9 ± 4.2 days. Overall, 21 patients (58%) were weaned off ECLS, and 17 patients (47%) were successfully discharged from the hospital. Patients with biventricular heart (BVH) had higher survival-to-hospital discharge rates compared with those with univentricular heart (UVH) (P = 0.019). Regarding ECLS type, UVH patients who received VAS showed higher rates of device discontinuation than UVH patients who received ECMO (P = 0.012). However, rates of hospital discharge were not significantly different between UVH patients who received VAS or ECMO. Surgical interventions, such as banding of Blalock-Taussig shunt to reduce pulmonary blood flow or placing bidirectional cavopulmonary shunt to minimize ventricular volume overload, were effective for weaning off ECLS in patients with UVH. ECLS is beneficial to children with low cardiac output after cardiac surgery. Rates of survival-to-hospital discharge were higher in BVH patients than UVH patients. Additional interventions to reduce ventricular volume load may be effective for discontinuing ECLS in patients with UVH. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  11. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  12. Evaluation of thermal overload in boiler operators.

    Science.gov (United States)

    Braga, Camila Soares; Rodrigues, Valéria Antônia Justino; Campos, Julio César Costa; de Souza, Amaury Paulo; Minette, Luciano José; de Moraes, Angêlo Casali; Sensato, Guilherme Luciano

    2012-01-01

    The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload.

  13. Planetary Overload, Limits to Growth and Health.

    Science.gov (United States)

    Butler, Colin D

    2016-12-01

    Since the use of atomic weapons in 1945 visionaries have warned that without major changes the survival of global civilization is in question. These concerns deepened in following decades, during the Cold War, with The Limits to Growth, the best-selling environmental book of the 1970s. Yet, since then, most concern has faded, fuelled by technological developments and a shift in dominant global ideology. Public health, with a few exceptions (one of which is the book Planetary Overload), has been slow to recognize this debate, even as evidence emerges that civilization may indeed be at risk, driven by an increasingly ominous complex of events. This article outlines the key relevant literature and concepts, attempting to bring emerging and future health consequences to the attention of health workers, including the idea of a "social vaccine," conveying sufficient anxiety to provoke action for environmental protection, but insufficient to induce paralysis.

  14. Avoiding Program-Induced Cumulative Overload (PICO).

    Science.gov (United States)

    Orr, Robin; Knapik, Joseph J; Pope, Rodney

    2016-01-01

    This article defines the concept of program-induced cumulative overload (PICO), provides examples, and advises ways to mitigate the adverse effects. PICO is the excessive cumulative physical workload that can be imparted to military personnel by a military training program with an embedded physical training component. PICO can be acute (accumulating within a single day) or chronic (accumulating across the entirety of the program) and results in adverse outcomes for affected personnel, including detrimental fatigue, performance degradation, injuries, or illness. Strategies to mitigate PICO include focusing administration and logistic practices during the development and ongoing management of a trainee program and implementing known musculoskeletal injury prevention strategies. More training is not always better, and trainers need to consider the total amount of physical activity that military personnel experience across both operational training and physical training if PICO is to be mitigated. 2016.

  15. Cardiac T1 Imaging

    OpenAIRE

    Jerosch-Herold, Michael; Kwong, Raymond Y.

    2014-01-01

    T1 mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extra-cellular volume (expansion), and most recently cardiomyocyte hypertrophy. The MRI pulse sequence techniques developed for these applications have had to address at least two important considerations for cardiac applications: measure magnetization inversion recoveries during cardiac motion w...

  16. Cardiac Ankyrin Repeat Protein Attenuates Cardiac Hypertrophy by Inhibition of ERK1/2 and TGF-β Signaling Pathways

    Science.gov (United States)

    Jia, Chunshi; Ma, Xiaowei; Zhang, Lei; Xie, Xiaojie; Zhang, Yong; Gao, Xiang; Zhang, Youyi; Zhu, Dahai

    2012-01-01

    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. PMID:23227174

  17. Interrelations of Epicardial Fat Volume, Left Ventricular T1-Relaxation Times and Myocardial Strain in Hypertensive Patients: A Cardiac Magnetic Resonance Study.

    Science.gov (United States)

    Homsi, Rami; Kuetting, Daniel; Sprinkart, Alois; Steinfeld, Nina; Meier-Schroers, Michael; Luetkens, Julian; Nadal, Jennifer; Dabir, Darius; Fischer, Stefan; Gieseke, Juergen; Schild, Hans; Thomas, Daniel

    2017-05-01

    This cardiac magnetic resonance study was performed to assess myocardial fibrosis by evaluating T1-relaxation time (T1), to measure left ventricular (LV) strain, and to determine epicardial fat volume (EFV) in hypertensive patients with no history of cardiovascular (CV) events and to relate the results to the presence of coronary atherosclerotic artery disease (CAD) in these patients. A total of 123 subjects were examined at 1.5 T. Of them, 98 were hypertensive patients (58 men; mean age, 62.9±10.7 y; body mass index, 29.0±5.6 kg/m) and 25 were controls without CV risk factors or disease (13 men; 60.1±10.7 y; 28.1±5.4 kg/m). All patients had a well-treated blood pressure. In the hypertensive group, 56 patients had no CAD, whereas 42 patients had CAD. T1 was assessed by a modified Look-Locker inversion recovery sequence. Longitudinal and circumferential peak systolic strain (LS; CS) was determined with dedicated cardiac magnetic resonance software (feature tracking). EFV (normalized to the body surface area) was assessed by a 3D Dixon sequence. T1 (ms) and EFV (mL/m) were higher and CS and LS (%) were lower in hypertensive patients compared with those in nonhypertensive controls (PEFV=58.2±21.1; hypertensive patients overall: T1=991.3±45.5, LS=-21.0±4.5, CS=-25.0±5.9, EFV=71.1±25.3; hypertensive patients without CAD: T1=991.6±48.4, LS=-21.0±4.7, CS=-24.6±6.3, EFV=71.3±26.6; hypertensive patients with CAD: T1=986.7±39.2, LS=-21.1±4.3, CS=-25.5±5.4, EFV=70.9±23.6). There were no significant differences between hypertensive patients with and those without CAD and between patients grouped according to the number of vessels affected (0-vessel disease, 1-vessel disease, 2-vessel disease, or 3-vessel disease). Hypertension is associated with signs of myocardial fibrosis and an impaired LV contractility despite a normal LV ejection fraction, as well as with an increased EFV. However, CAD, in the absence of previous pathologies with consecutive myocardial

  18. Quantitative analysis of epicardial fat volume: effects of scanning protocol and reproducibility of measurements in non-contrast cardiac CT vs. coronary CT angiography.

    Science.gov (United States)

    D'Errico, Luigia; Salituri, Francesco; Ciardetti, Marco; Favilla, Riccardo; Mazzarisi, Alessandro; Coppini, Giuseppe; Bartolozzi, Carlo; Marraccini, Paoli

    2017-06-01

    Several studies have focused on the role of epicardial fat in the pathogenesis of cardiovascular disease (CVD). The main purpose of the study was to evaluate a computerized method for the quantitative analysis of epicardial fat volume (EFV) by non-contrast cardiac CT (NCT) for coronary calcium scan and coronary CT angiography (coronary CTA). Thirty patients (61±12.5 years, 73% male, body mass index (BMI) =25.9±6.3 kg/m2) referred to our Institution for suspected coronary artery disease (CAD) underwent NCT and coronary CTA. Epicardial boundaries were traced by 2 experienced operators (operator 1, operators 2) on 3 and 6 short-axis (SA) slices. EFV was computed with a semi-automatic method using an in-house developed software based on spherical harmonic representation of the epicardial surface. In order to analyze the inter-observer variability both the Coefficient of Repeatability (CR) and Intra Class Correlation (ICC) were computed. The total EFV was 103.62±50.97 and 94.96±67.91 cc in NCT and coronary CTA with non-significant difference (P=0.292). CR error was 10.22 cc for operator 1 and 11.31 cc for operator 2 in NCT and 7.99 cc for operator 1 and 7.75 cc for operator 2 in coronary CTA. To analyze the inter-observer variability CR and ICC were computed. CR was 8.17 and 8.39 cc with NCT and 7.07 and 7.21 cc with CTA for 6 and 3 SA slices respectively. ICC values >0.99 were obtained in all cases. The right ventricular EFV was 67.23±31.4 and 57.41±34.3 cc for NCT and coronary CTA respectively; the corresponding values for left ventricular EFV were 38.01±19.1 and 35.27±25.9 cc. Both NCT and coronary CTA can be used with low intra- and inter-observer variability for computer-assisted measurements of EFV. Cardiac CT may allow a fast and reliable computation of EFV in clinical setting.

  19. 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.

  20. The plasma membrane calcium ATPase 4 signalling in cardiac fibroblasts mediates cardiomyocyte hypertrophy

    Science.gov (United States)

    Mohamed, Tamer M. A.; Abou-Leisa, Riham; Stafford, Nicholas; Maqsood, Arfa; Zi, Min; Prehar, Sukhpal; Baudoin-Stanley, Florence; Wang, Xin; Neyses, Ludwig; Cartwright, Elizabeth J.; Oceandy, Delvac

    2016-01-01

    The heart responds to pathological overload through myocyte hypertrophy. Here we show that this response is regulated by cardiac fibroblasts via a paracrine mechanism involving plasma membrane calcium ATPase 4 (PMCA4). Pmca4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out Pmca4 specifically in cardiomyocytes does not produce this effect. Mechanistically, cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes. Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a therapeutic approach to treat this condition. PMID:27020607

  1. Cardiac catheterization - discharge

    Science.gov (United States)

    Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary ...

  2. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats.

    Directory of Open Access Journals (Sweden)

    Daniela Farah

    Full Text Available The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group: Sedentary control (SC, Trained control (TC, Sedentary Fructose (SF and Trained Fructose (TF. Training was performed on a treadmill (8 weeks, 40-60% of maximum exercise test. Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT weight, in myocardial performance index (MPI (SF:0.42±0.04 vs. SC:0.24±0.05 and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox. The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04, arterial pressure (118±2mmHg, sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training.

  3. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats.

    Science.gov (United States)

    Farah, Daniela; Nunes, Jonas; Sartori, Michelle; Dias, Danielle da Silva; Sirvente, Raquel; Silva, Maikon B; Fiorino, Patrícia; Morris, Mariana; Llesuy, Susana; Farah, Vera; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2016-01-01

    The risks of chronic diseases associated with the increasing consumption of fructose-laden foods are amplified by the lack of regular physical activity and have become a serious public health issue worldwide. Moreover, childhood eating habits are strongly related to metabolic syndrome in adults. Thus, we aimed to investigate the preventive role of exercise training undertaken concurrently with a high fructose diet on cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in male rats after weaning. Male Wistar rats were divided into 4 groups (n = 8/group): Sedentary control (SC), Trained control (TC), Sedentary Fructose (SF) and Trained Fructose (TF). Training was performed on a treadmill (8 weeks, 40-60% of maximum exercise test). Evaluations of cardiac function, hemodynamics, cardiovascular autonomic modulation and oxidative stress in plasma and in left ventricle (LV) were performed. Chronic fructose overload induced glucose intolerance and an increase in white adipose tissue (WAT) weight, in myocardial performance index (MPI) (SF:0.42±0.04 vs. SC:0.24±0.05) and in arterial pressure (SF:122±3 vs. SC:113±1 mmHg) associated with increased cardiac and vascular sympathetic modulation. Fructose also induced unfavorable changes in oxidative stress profile (plasmatic protein oxidation- SF:3.30±0.09 vs. SC:1.45±0.08 nmol/mg prot; and LV total antioxidant capacity (TRAP)- SF: 2.5±0.5 vs. SC:12.7±1.7 uM trolox). The TF group showed reduced WAT, glucose intolerance, MPI (0.35±0.04), arterial pressure (118±2mmHg), sympathetic modulation, plasmatic protein oxidation and increased TRAP when compared to SF group. Therefore, our findings indicate that cardiometabolic dysfunctions induced by fructose overload early in life may be prevented by moderate aerobic exercise training.

  4. Ability of pulse wave transit time to detect changes in stroke volume and to estimate cardiac output compared to thermodilution technique in isoflurane-anaesthetised dogs.

    Science.gov (United States)

    Sano, H; Chambers, J P

    2017-04-26

    To evaluate the ability of pulse wave transit time (PWTT) to detect changes in stroke volume (SV) and to estimate cardiac output (CO) compared with the thermodilution technique in isoflurane-anaesthetized dogs. Prospective, experimental study. Eight adult laboratory dogs. The dogs were anaesthetized with isoflurane and mechanically ventilated. Reference CO (TDCO) was measured via a pulmonary artery catheter using the thermodilution technique and reference SV (TDSV) was calculated. PWTT was calculated as the time from the electrocardiogram R-wave peak to the rise point of the pulse oximeter wave. Estimated CO (esCO) was derived from PWTT after calibration with arterial pulse pressure (both non-invasive and invasive methods) and TDCO. Haemodynamic changes were induced by administration of phenylephrine (vasoconstriction), high isoflurane (vasodilatation and negative inotropy) and dobutamine (vasodilatation and positive inotropy). Trending between percentage change in PWTT and TDSV was assessed using concordance analysis and receiver operator characteristic (ROC) curve. The agreement between esCO and TDCO was evaluated using the Bland-Altman method. The direction of percentage change between consecutive PWTT and the corresponding TDSV showed a concordance rate of 95%, with correlation coefficients of -0.86 (pblood pressure showed a bias (precision of agreement) of 0.58 (1.54) and 0.57 (1.59) L minute(-1) with a percentage error of ±61% and ±63%, respectively. In isoflurane-anaesthetized dogs, PWTT showed a good trending ability to detect 15% changes in SV. This technique is easy to use, inexpensive, non-invasive and could become routine anaesthetic monitoring. However, the agreement between absolute esCO and TDCO was unacceptable. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  5. Cardiac magnetic resonance based evaluation of aortic stiffness and epicardial fat volume in patients with hypertension, diabetes mellitus, and myocardial infarction.

    Science.gov (United States)

    Homsi, Rami; Sprinkart, Alois M; Gieseke, Juergen; Meier-Schroers, Michael; Yuecel, Seyrani; Fischer, Stefan; Nadal, Jennifer; Dabir, Darius; Luetkens, Julian A; Kuetting, Daniel L; Schild, Hans H; Thomas, Daniel K

    2018-01-01

    Background Aortic stiffness and epicardial fat relate to cardiovascular risk. Their relationship with each other and their role with hypertension, diabetes mellitus (DM), and myocardial infarction (MI) can be evaluated by cardiac magnetic resonance (CMR). Purpose To explore an association between aortic stiffness and epicardial as well as paracardial fat volume (EFV and ParaFV, respectively) in hypertensive patients and to relate the results to the presence of DM and MI. Material and Methods A total of 156 hypertensive and 20 non-hypertensive participants were examined at 1.5 Tesla. A 2D-velocity-encoded sequence was acquired to assess aortic pulse wave velocity (PWV in m/s) as a measure of aortic stiffness. A 3D-Dixon sequence was used to determine EFV and ParaFV. Results PWV correlated with EFV (R = 0.474; P hypertensive controls compared to hypertensive patients. EFV and PWV were significantly higher in diabetic hypertensive patients without MI (n = 19; PWV: 10.4 ± 2.9; EFV: 92.5 ± 19.3) compared to hypertension-only patients (n = 84 [no DM or MI]; EFV: 64.8 ± 25.1, PWV: 9.0 ± 2.6; P hypertensive patients. Both were increased in the presence of DM; however, only EFV was increased in the presence of MI. This may relate to the PWV lowering effect of the antihypertensive medication used by hypertensive patients and underscores the benefit of EFV assessment in this regard.

  6. Left Atrial Volume as a Predictor of Left Ventricular Functional Recovery in Patients With Dilated Cardiomyopathy and Absence of Delayed Enhancement in Cardiac Magnetic Resonance.

    Science.gov (United States)

    Moon, Jeonggeun; Shim, Chi Young; Kim, Young-Jin; Park, Sungha; Kang, Seok-Min; Chung, Namsik; Ha, Jong-Won

    2016-04-01

    Improvement of left ventricular (LV) systolic dysfunction can occur in patients with dilated cardiomyopathy (DCM), and it is more frequently observed if patients have no delayed enhancement (DE) in cardiac magnetic resonance imaging (CMR). However, even in the absence of DE, not all patients have functional recovery. We retrospectively investigated the predictors of LV functional recovery in patients with DCM who had no DE in CMR. A total of 136 patients with DCM underwent CMR. Among them, 44 (29 male, age 55 ± 14 years) showed no DE and these patients composed the study population. The study patients were divided into 2 groups according to the occurrence of functional recovery defined as an increase in LV ejection fraction to a level of ≥50% and net increase in ejection fraction of 20% or more: group 1 (n = 14) with functional recovery and group 2 (n = 30) without functional recovery. In patients who showed functional recovery, left atrial volume index (LAVI [26 ± 8 mL/m(2) vs 45 ± 18 mL/m(2)]) and LV end-diastolic dimension (62 ± 6 mm vs 67 ± 7 mm) were significantly smaller when compared with those without functional recovery (P functional recovery (hazard ratio 0.932, 95% confidence interval 0.877-0.991, P = .024). LAVI functional recovery with high specificity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The effect of head up tilting on bioreactance cardiac output and stroke volume readings using suprasternal transcutaneous Doppler as a control in healthy young adults.

    Science.gov (United States)

    Zhang, Jie; Critchley, Lester A H; Lee, Daniel C W; Khaw, Kim S; Lee, Shara W Y

    2016-10-01

    To compare the performance of a bioreactance cardiac output (CO) monitor (NICOM) and transcutaneous Doppler (USCOM) during head up tilting (HUT). Healthy young adult subjects, age 22 ± 1 years, 7 male and 7 female, were tilted over 3-5 s from supine to 70° HUT, 30° HUT and back to supine. Positions were held for 3 min. Simultaneous readings of NICOM and USCOM were performed 30 s into each new position. Mean blood pressure (MBP), heart rate (HR), CO and stroke volume (SV), and thoracic fluid content (TFC) were recorded. Bland-Altman, percentage changes and analysis of variance for repeated measures were used for statistical analysis. Pre-tilt NICOM CO and SV readings (6.1 ± 1.0 L/min and 113 ± 25 ml) were higher than those from USCOM (4.1 ± 0.6 L/min and 77 ± 9 ml) (P effect proportional changes in SV readings of 23 ± 15 % (30° half tilt) and 44 ± 11 % (70° near full tilt), NICOM changes did not being 28 ± 10 and 33 ± 11 %. TFC decreased linearly with HUT. The NICOM does not provide linear changes in SV as predicted by physiology when patients are tilted. Furthermore there is a lack of agreement with USCOM measurements at baseline and during tilting.

  8. Efficacy and Safety of Renal Sympathetic Denervation on Dogs with Pressure Overload-Induced Heart Failure.

    Science.gov (United States)

    Chen, Pingan; Leng, Shuilong; Luo, Yishan; Li, Shaonan; Huang, Zicheng; Liu, Zhenxi; Liu, Zhen; Wang, Jie; Lei, Xiaoming

    2017-02-01

    In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62±6.84 vs. 183.48±13.66 pg/ml, P<0.05), plasma renin activity (1.93±0.12 vs. 2.10±0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14±3.86 vs. 83.15±5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  9. Obesity versus osteoarthritis: beyond the mechanical overload.

    Science.gov (United States)

    Sartori-Cintra, Angélica Rossi; Aikawa, Priscila; Cintra, Dennys Esper Correa

    2014-09-01

    Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis.

  10. [Navigation aid through the information overload].

    Science.gov (United States)

    Günther, Judith; Schindler, Birgit; Suter, Katja

    2014-10-01

    We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner.

  11. Overload truck wheel load distribution on bridge decks.

    Science.gov (United States)

    2009-04-01

    There is a need to accurately analyze the load effects on bridge decks from permitted overload trucks on : Michigans roads. The AASHTO Standard Specifications for Highway Bridges, 17th edition, provides a : distribution width of live loads when re...

  12. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

    OpenAIRE

    Yusra Habib Khan; Azmi Sarriff; Azreen Syazril Adnan; Amer Hayat Khan; Tauqeer Hussain Mallhi

    2016-01-01

    Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by...

  13. Application of Chaos Theory in Trucks' Overloading Enforcement

    Directory of Open Access Journals (Sweden)

    Abbas Mahmoudabadi

    2013-01-01

    Full Text Available Trucks' overloading is considered as one of the most substantial concerns in road transport due to a possible road surface damage, as well as, are less reliable performance of trucks' braking system. Sufficient human resource and adequate time scheduling are to be planned for surveying trucks' overloading; hence, it seems required to prepare an all-around model to be able to predict the number of overloaded vehicles. In the present research work, the concept of chaos theory has been utilized to predict the ratio of trucks which might be guessed overloaded. The largest Lyapunov exponent is utilized to determine the presence of chaos using experimental data and concluded that the ratio of overloaded trucks reflects chaotic behavior. The prediction based on chaos theory is compared with the results of simple smoothing and moving average methods according to the well-known criterion of mean square errors. The results have also revealed that the chaotic prediction model would act more capably comparing the analogous methods including simple smoothing and moving average to predict the ratio of passing trucks to be possibly overloaded.

  14. Nutritional Status and Cardiac Autophagy

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    Jihyun Ahn

    2013-02-01

    Full Text Available Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

  15. Prospective observational study for perioperative volume replacement with 6% HES 130/0,42, 4% gelatin and 6% HES 200/0,5 in cardiac surgery

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    Winterhalter M

    2010-09-01

    Full Text Available Abstract Background The constantly growing amount of different kinds of colloid fluids necessitates comparative investigations with regards to the safety and effectivity in clinical use of these preparations. Hence we compared three colloid fluids in an observational study. The objective was the exploration of the influence of these three colloids on blood coagulation, hemodynamics and renal function of the cardiac surgical patient. Methods We included 90 patients undergoing an elective open-heart surgery with the use of the heart-lung machine and observed them consecutively. Group 1 [gelatin 4% (n = 30], Group 2 [HES 200/0,5 (n = 30] and Group 3 [HES 130/0,42 (n = 30]. We measured the perioperative volume replacement, the administration of blood- and coagulation-products, the application of catecholamines, the renal function, blood gas and the platelet aggregation using multiplate electrode analyzer (Multiplate®, Dynabyte medical, Munich, Germany. Results The gelatin-group needed significantly more norepinephrine than the HES 130/0.42 group. The responsible surgeon considered the blood coagulation in the HES 200/0.5 group most frequently as impaired. Furthermore we saw a significant decrease in platelet function in the HES 200/0.5 group when performing the multiplate®-analysis (ADP-and COL-test. HES 130/0.4 as well as gelatin 4% showed no significant change in platelet function. The gelatin-group and the HES 200/0.5 needed significantly more aprotinine than the HES 130/0.4 group. We saw no significant difference with regards to administration of blood and coagulation products between the three groups. The urinary excretion during the intervention was significantly higher in the HES 200/0.5 group and in the gelatin group than in the HES 130/0.4 group. Conclusions Our results confirm the lower stabilizing effect of gelatin on circulation during fluid resuscitation. The blood coagulation was mostly impaired due to HES 200/0.5 confirmed by the

  16. Multimedia reviews: multimedia overload produces "symplexity".

    Science.gov (United States)

    Zingrone, Frank

    2003-03-01

    We humans "know" from information mediated through our "natural senses." All outside signals come to us through some medium-sound waves, pressure and touch, light waves, radio and television waves, and so forth. McLuhan's famous mantra "The medium is the message" paradoxically highlighted the critical transformation of meaning when each type of medium-radio, television, drums, hand signals-by its very nature modifies the message it is transmitting. In this month's column Dr. Zingrone brings challenging new ideas to the field of human communication and vividly describes the communication distortions that occur when the overload of increasingly complex modern media results in a paradoxical diminution of meaning itself. He has coined a term for this unintended consequence and given it to his exciting new book, The Media Symplex: At the Edge of Meaning in the Age of Chaos (1). Many of us may recognize the effect created by this accelerating phenomenon-our stupefaction as we experience the onslaught of sound and visual signals produced by a television news screen, where an avalanche of rapidly changing, overlapping, and distorted visual images flash at our eyes while screeching, undulating synthetic "music" crashes about our ears. And in that chaos we struggle to find meaning,Dr. Zingrone, who worked with McLuhan and who has written extensively about his work (2,3), has succeeded in his new book to move the pioneering work of human communication scientists forward and thereby help us all to understand the developing paradox and danger of more communication yet less meaning.

  17. Apoptosis of cardiomyocytes in children with right ventricular pressure overload with and without hypoxemia.

    Science.gov (United States)

    Tsang, Flora Hau Fung; Chow, Pak-Cheong; Ma, Yuen-Yuen; Man, Kwan; Cheng, Lik-Cheung; Cheung, Yiu-Fai

    2014-07-01

    Cardiomyocyte apoptosis has been implicated in ventricular remodeling and initiation of cardiac failure. We sought to determine the severity of right ventricular (RV) cardiomyocyte apoptosis in cyanotic and acyanotic children with RV pressure overload. Fourteen patients, seven with tetralogy of Fallot (group I) and seven with pulmonary stenosis and ventricular septal defect (group II), undergoing open-heart surgery were studied. Right ventricular biopsies were examined for cardiomyocyte apoptosis by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. The magnitude of cardiomyocyte apoptosis was related to preoperative oxygen saturation and postoperative inotrope use and hospital stay. Compared with group I patients, group II patients were significantly older at operation (p = 0.002) and had a larger body size (p right ventricle is related to the severity of hypoxia and may have an impact on postoperative course in terms of early postoperative use of inotropes and duration of hospital stay. © 2014 Wiley Periodicals, Inc.

  18. The Impact of a Targeted Training Program on E-Mail System Processing Capabilities and Self-Perception of E-Mail Overload

    Science.gov (United States)

    Einstein, Michael M.

    2014-01-01

    As business e-mail volumes continue to grow and employees spend increasingly larger portions of their day processing e-mail, there is strong evidence of the negative impacts of e-mail processing, especially with respect to e-mail overload. This study sought to determine whether a training program focused on select e-mail features and processing…

  19. Cardiac hypertrophy caused by peroxisome proliferator- activated receptor-gamma agonist treatment occurs independently of changes in myocardial insulin signaling.

    Science.gov (United States)

    Sena, Sandra; Rasmussen, Isaac R; Wende, Adam R; McQueen, Alfred P; Theobald, Heather A; Wilde, Nicole; Pereira, Renata Oliveira; Litwin, Sheldon E; Berger, Joel P; Abel, E Dale

    2007-12-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma ligands are insulin sensitizers, widely used in the treatment of type 2 diabetes. A consistent observation in preclinical species is the development of cardiac hypertrophy after short-term treatment with these agents. The mechanisms for this hypertrophy are incompletely understood. Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-gamma ligand-induced cardiac hypertrophy. We treated mice with cardiomyocyte-restricted knockout of insulin receptors (CIRKO) and littermate controls (wild type) with 2-(2-(4-phenoxy-2-propylphenoxy) ethyl) indole-5-acetic acid (COOH), which is a non-thiazolidinedione PPAR-gamma agonist for 2 wk. Two weeks of COOH treatment increased heart weights by 22% in CIRKO mice and 16% in wild type, and induced similar fold increase in the expression of hypertrophic markers such as alpha-skeletal actin, brain natriuretic peptide, and atrial natriuretic peptide in CIRKO and wild-type (WT) hearts. COOH treatment increased plasma volume by 10% in COOH-treated WT and CIRKO mice but did not increase systolic or diastolic blood pressure. Echocardiographic analysis was also consistent with volume overload, as evidenced by increased left ventricular diastolic diameters and cardiac output in COOH-treated CIRKO and WT mice. These data indicate that cardiac hypertrophy after PPAR-gamma agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion.

  20. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available Iron overload cardiomyopathy results from iron accumulation in the myocardium that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza (SM, also known as Danshen, a traditional Chinese medicinal herb, has been widely used for hundreds of years to treat cardiovascular diseases. Here, we investigated the effect and potential mechanism of SM on myocardial fibrosis induced by chronic iron overload (CIO in mice. Kunming male mice (8 weeks old were randomized to six groups of 10 animals each: control (CONT, CIO, low-dose SM (L-SM, high-dose SM (H-SM, verapamil (VRP and deferoxamine (DFO groups. Normal saline was injected in the CONT group. Mice in the other five groups were treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and those in the latter four groups also received corresponding daily treatments, including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron deposition was estimated histologically using Prussian blue staining. Myocardial fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp quantitative assay. Superoxide dismutase (SOD activity, malondialdehyde (MDA content and protein expression levels of type I collagen (COL I, type I collagen (COL III, transforming growth factor-β1 (TGF-β1 and matrix metalloproteinase-9 (MMP-9 were analyzed to investigate the mechanisms underlying the effects of SM against iron-overloaded fibrosis. Treatment of chronic iron-overloaded mice with SM dose-dependently reduced iron deposition levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL III, as well as upregulated the expression of TGF- β1 and MMP-9 proteins in the heart. Moreover, SM treatment decreased MDA content and increased SOD activity. In conclusion, SM exerted activities against cardiac fibrosis induced by CIO, which may be attributed to its inhibition of iron deposition, as well as collagen metabolism and oxidative

  1. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

    Science.gov (United States)

    Fujiu, Katsuhito; Shibata, Munehiko; Nakayama, Yukiteru; Ogata, Fusa; Matsumoto, Sahohime; Noshita, Koji; Iwami, Shingo; Nakae, Susumu; Komuro, Issei; Nagai, Ryozo; Manabe, Ichiro

    2017-05-01

    Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6Clo macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6Clo macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

  2. Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

    Science.gov (United States)

    Tale, V P; Maki, J S; Zitomer, D H

    2015-03-01

    Adding beneficial microorganisms to anaerobic digesters for improved performance (i.e. bioaugmentation) has been shown to decrease recovery time after organic overload or toxicity upset. Compared to strictly anaerobic cultures, adding aerotolerant methanogenic cultures may be more practical since they exhibit higher methanogenic activity and can be easily dried and stored in ambient air for future shipping and use. In this study, anaerobic digesters were bioaugmented with both anaerobic and aerated, methanogenic propionate enrichment cultures after a transient organic overload. Digesters bioaugmented with anaerobic and moderately aerated cultures recovered 25 and 100 days before non-bioaugmented digesters, respectively. Increased methane production due to bioaugmentation continued a long time, with 50-120% increases 6 to 12 SRTs (60-120 days) after overload. In contrast to the anaerobic enrichment, the aerated enrichments were more effective as bioaugmentation cultures, resulting in faster recovery of upset digester methane and COD removal rates. Sixty days after overload, the bioaugmented digester archaeal community was not shifted, but was restored to one similar to the pre-overload community. In contrast, non-bioaugmented digester archaeal communities before and after overload were significantly different. Organisms most similar to Methanospirillum hungatei had higher relative abundance in well-operating, undisturbed and bioaugmented digesters, whereas organisms similar to Methanolinea tarda were more abundant in upset, non-bioaugmented digesters. Bioaugmentation is a beneficial approach to increase digester recovery rate after transient organic overload events. Moderately aerated, methanogenic propionate enrichment cultures were more beneficial augments than a strictly anaerobic enrichment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Automated quantification of mitral regurgitation by three dimensional real time full volume color Doppler transthoracic echocardiography: a validation with cardiac magnetic resonance imaging and comparison with two dimensional quantitative methods.

    Science.gov (United States)

    Son, Jang-Won; Chang, Hyuk-Jae; Lee, Jin-Kyung; Chung, Hee-Jung; Song, Ran-Young; Kim, Young-Jin; Datta, Saurabh; Heo, Ran; Shin, Sang-Hoon; Cho, In-Jeong; Shim, Chi Young; Hong, Geu-Ru; Chung, Namsik

    2013-06-01

    Accurate assessment of mitral regurgitation (MR) severity is crucial for clinical decision-making and optimizing patient outcomes. Recent advances in real-time three dimensional (3D) echocardiography provide the option of real-time full volume color Doppler echocardiography (FVCD) measurements. This makes it practical to quantify MR by subtracting aortic stroke volume from the volume of mitral inflow in an automated manner. Thirty-two patients with more than a moderate degree of MR assessed by transthoracic echocardiography (TTE) were consecutively enrolled during this study. MR volume was measured by 1) two dimensional (2D) Doppler TTE, using the proximal isovelocity surface area (PISA) and the volumetric quantification methods (VM). Then, 2) real time 3D-FVCD was subsequently obtained, and dedicated software was used to quantify the MR volume. MR volume was also measured using 3) phase contrast cardiac magnetic resonance imaging (PC-CMR). In each patient, all these measurements were obtained within the same day. Automated MR quantification was feasible in 30 of 32 patients. The mean regurgitant volume quantified by 2D-PISA, 2D-VM, 3D-FVCD, and PC-CMR was 72.1 ± 27.7, 79.9 ± 36.9, 69.9 ± 31.5, and 64.2 ± 30.7 mL, respectively (p = 0.304). There was an excellent correlation between the MR volume measured by PC-CMR and 3D-FVCD (r = 0.85, 95% CI 0.70-0.93, p PISA or 2D-VM (60.0 and 62.8 mL, respectively). Automated quantification of MR with 3D-FVCD is feasible and accurate. It is a promising tool for the real-time 3D echocardiographic assessment of patients with MR.

  4. Cardiac Hemosiderosis in Transfusion DependentThalassemia: A Mini-Review

    Directory of Open Access Journals (Sweden)

    Ali Bazi

    2017-03-01

    Full Text Available Iron toxicity within cardiomyocytes is considered as the main pathogenesis of cardiac dysfunction in transfusion dependent thalassemia (TDT. Various methods such as measuring serum ferritin, evaluating cardiac functional and structural parameters by either cardiac magnetic resonance imaging (CMRI or echocardiography, and monitoring the heart rate variability (HRV have been proposed to monitor cardiac iron content in patients. High inconsistency is present regarding predictability of various parameters derived by each of these methods in order to predict the cardiac iron overload. The aim of present review was to grasp the most appropriate parameters predicting cardiac hemosiderosis in TDT. Predicating values for cardiac iron deposition of the most in-use indicators such as ferritin, cardiac T2* relaxation time, left ventricular ejection fraction (LVEF, and HRV were discussed. In addition, a description on the most effective preventive measures for cardiac hemosiderosis was provided.

  5. Identification of genes regulated during mechanical load-induced cardiac hypertrophy

    Science.gov (United States)

    Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

    2000-01-01

    Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

  6. Fat overload syndrome after the rapid infusion of SMOFlipid emulsion.

    Science.gov (United States)

    Hojsak, Iva; Kolaček, Sanja

    2014-01-01

    Fat overload syndrome is a well-known complication of intravenous lipid emulsion therapy. It is characterized by headaches, fever, jaundice, hepatosplenomegaly, respiratory distress, and spontaneous hemorrhage. Other symptoms include anemia, leukopenia, thrombocytopenia, low fibrinogen levels, and coagulopathy. Several reports in the literature describe fat overload syndrome caused by rapid infusion of lipid emulsions, all with soybean-based lipid emulsions. We report fat overload syndrome in a 2-year-old girl with short bowel syndrome on home parenteral nutrition. Fat overload syndrome occurred as a result of accidental, very rapid infusion of a 20% soy oil, medium-chain triglyceride, olive and fish oil-based lipid emulsion (SMOFlipid) that showed the same complications seen with an earlier lipid emulsion (Intralipid). The patient was successfully treated with supportive care combining fluid infusion, transfusion of platelets, and substitution of serum albumin (0.5 g/kg/d) and fresh-frozen plasma (10 mL/kg). In the next couple of days, she received extra platelets, erythrocyte transfusion, and filgrastim (Neupogen; 5 µg/kg/d) due to a very low leukocyte count. To the best of our knowledge, this is the first case of fat overload syndrome caused by SMOFlipid emulsion described in the literature.

  7. Cardiac output measurement

    Directory of Open Access Journals (Sweden)

    Andreja Möller Petrun

    2014-02-01

    Full Text Available In recent years, developments in the measuring of cardiac output and other haemodynamic variables are focused on the so-called minimally invasive methods. The aim of these methods is to simplify the management of high-risk and haemodynamically unstable patients. Due to the need of invasive approach and the possibility of serious complications the use of pulmonary artery catheter has decreased. This article describes the methods for measuring cardiac output, which are based on volume measurement (Fick method, indicator dilution method, pulse wave analysis, Doppler effect, and electrical bioimpedance.

  8. The added value of cardiac index and pulse pressure variation monitoring to mean arterial pressure-guided volume therapy in moderate-risk abdominal surgery (COGUIDE): a pragmatic multicentre randomised controlled trial.

    Science.gov (United States)

    Stens, J; Hering, J-P; van der Hoeven, C W P; Boom, A; Traast, H S; Garmers, L E; Loer, S A; Boer, C

    2017-09-01

    There is disagreement regarding the benefits of goal-directed therapy in moderate-risk abdominal surgery. Therefore, we tested the hypothesis that the addition of non-invasive cardiac index and pulse pressure variation monitoring to mean arterial pressure-based goal-directed therapy would reduce the incidence of postoperative complications in patients having moderate-risk abdominal surgery. In this pragmatic multicentre randomised controlled trial, we randomly allocated 244 patients by envelope drawing in a 1:1 fashion, stratified per centre. All patients had mean arterial pressure, cardiac index and pulse pressure variation measured continuously. In one group, healthcare professionals were blinded to cardiac index and pulse pressure variation values and were asked to guide haemodynamic therapy only based on mean arterial pressure (control group). In the second group, cardiac index and pulse pressure variation values were displayed and kept within target ranges following a pre-defined algorithm (CI-PPV group). The primary endpoint was the incidence of postoperative complications within 30 days. One hundred and seventy-five patients were eligible for final analysis. Overall complication rates were similar (42/94 (44.7%) vs. 38/81 (46.9%) in the control and CI-PPV groups, respectively; p = 0.95). The CI-PPV group had lower mean (SD) pulse pressure variation values (9.5 (2.0)% vs. 11.9 (4.6)%; p = 0.003) and higher mean (SD) cardiac indices (2.76 (0.62) l min-1 .m-2 vs. 2.53 (0.66) l min-1 .m-2 ; p = 0.004) than the control group. In moderate-risk abdominal surgery, we observed no additional value of cardiac index and pulse pressure variation-guided haemodynamic therapy to mean arterial pressure-guided volume therapy with regard to postoperative complications. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  9. Quantitative Positron Emission Tomography Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure Overload Left Ventricular Hypertrophy in vivo

    Science.gov (United States)

    Zhong, Min; Alonso, Clayton E.; Taegtmeyer, Heinrich; Kundu, Bijoy K.

    2013-01-01

    We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes

  10. Symmetrical and overloaded effect of diffusion in information filtering

    Science.gov (United States)

    Zhu, Xuzhen; Tian, Hui; Chen, Guilin; Cai, Shimin

    2017-10-01

    In physical dynamics, mass diffusion theory has been applied to design effective information filtering models on bipartite network. In previous works, researchers unilaterally believe objects' similarities are determined by single directional mass diffusion from the collected object to the uncollected, meanwhile, inadvertently ignore adverse influence of diffusion overload. It in some extent veils the essence of diffusion in physical dynamics and hurts the recommendation accuracy and diversity. After delicate investigation, we argue that symmetrical diffusion effectively discloses essence of mass diffusion, and high diffusion overload should be published. Accordingly, in this paper, we propose an symmetrical and overload penalized diffusion based model (SOPD), which shows excellent performances in extensive experiments on benchmark datasets Movielens and Netflix.

  11. Diagnosis and quantification of the iron overload through Magnetic resonance.

    Science.gov (United States)

    Alústiza Echeverría, J M; Barrera Portillo, M C; Guisasola Iñiguiz, A; Ugarte Muño, A

    There are different magnetic resonance techniques and models to quantify liver iron concentration. T2 relaxometry methods evaluate the iron concentration in the myocardium, and they are able to discriminate all the levels of iron overload in the liver. Signal intensity ratio methods saturate with high levels of liver overload and can not assess iron concentration in the myocardium but they are more accessible and are very standardized. This article reviews, in different clinical scenarios, when Magnetic Resonance must be used to assess iron overload in the liver and myocardium and analyzes the current challenges to optimize the aplication of the technique and to be it included in the clinical guidelines. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Overload Control in Smart Transformer-Fed Grid

    Directory of Open Access Journals (Sweden)

    Giovanni De Carne

    2017-02-01

    Full Text Available Renewable energy resources and new loads—such as electric vehicles—challenge grid management. Among several scenarios, the smart transformer represents a solution for simultaneously managing low- and medium-voltage grids, providing ancillary services to the distribution grid. However, unlike conventional transformers, the smart transformer has a very limited overload capability, because the junction temperature—which must always be below its maximum limit—is characterized by a short time constant. In this work, an overload control for smart transformer by means of voltage and frequency variations has been proposed and verified by means of simulations and experiments.

  13. Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

    2014-08-15

    Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

  14. Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery.

    Science.gov (United States)

    Mah, Kenneth E; Hao, Shiying; Sutherland, Scott M; Kwiatkowski, David M; Axelrod, David M; Almond, Christopher S; Krawczeski, Catherine D; Shin, Andrew Y

    2017-11-11

    Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI). This was a retrospective cohort study which examined neonates (age Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay. Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts ( 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.

  15. Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome

    Science.gov (United States)

    Ganda, Anjali; Lin, Jeffrey; Onat, Duygu; Harxhi, Ante; Iyasere, Julia E.; Uriel, Nir; Cotter, Gad

    2013-01-01

    Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of proinflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of proinflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients’ outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome. PMID:21688186

  16. Preload Sensitivity in Cardiac Assist Devices

    Science.gov (United States)

    Fukamachi, Kiyotaka; Shiose, Akira; Massiello, Alex; Horvath, David J.; Golding, Leonard A. R.; Lee, Sangjin; Starling, Randall C.

    2013-01-01

    With implantable cardiac assist devices increasingly proving their effectiveness as therapeutic options for end-stage heart failure, it is important for clinicians to understand the unique physiology of device-assisted circulation. Preload sensitivity as it relates to cardiac assist devices is derived from the Frank-Starling relationship between human ventricular filling pressures and ventricular stroke volume. In this review, we stratify the preload sensitivity of 17 implantable cardiac assist devices relative to the native heart and discuss the effect of preload sensitivity on left ventricular volume unloading, levels of cardiac support, and the future development of continuous-flow total artificial heart technology. PMID:23272869

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

    Science.gov (United States)

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

    2016-10-01

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

  18. The total right/left-volume index: a new and simplified cardiac magnetic resonance measure to evaluate the severity of Ebstein anomaly of the tricuspid valve: a comparison with heart failure markers from various modalities.

    Science.gov (United States)

    Hösch, Olga; Sohns, Jan Martin; Nguyen, Thuy-Trang; Lauerer, Peter; Rosenberg, Christina; Kowallick, Johannes Tammo; Kutty, Shelby; Unterberg, Christina; Schuster, Andreas; Faßhauer, Martin; Staab, Wieland; Paul, Thomas; Lotz, Joachim; Steinmetz, Michael

    2014-07-01

    The classification of clinical severity of Ebstein anomaly still remains a challenge. The aim of this study was to focus on the interaction of the pathologically altered right heart with the anatomically-supposedly-normal left heart and to derive from cardiac magnetic resonance (CMR) a simple imaging measure for the clinical severity of Ebstein anomaly. Twenty-five patients at a mean age of 26±14 years with unrepaired Ebstein anomaly were examined in a prospective study. Disease severity was classified using CMR volumes and functional measurements in comparison with heart failure markers from clinical data, ECG, laboratory and cardiopulmonary exercise testing, and echocardiography. All examinations were completed within 24 hours. A total right/left-volume index was defined from end-diastolic volume measurements in CMR: total right/left-volume index=(RA+aRV+fRV)/(LA+LV). Mean total right/left-volume index was 2.6±1.7 (normal values: 1.1±0.1). This new total right/left-volume index correlated with almost all clinically used biomarkers of heart failure: brain natriuretic peptide (r=0.691; P=0.0003), QRS (r=0.432; P=0.039), peak oxygen consumption/kg (r=-0.479; P=0.024), ventilatory response to carbon dioxide production at anaerobic threshold (r=0.426; P=0.048), the severity of tricuspid regurgitation (r=0.692; P=0.009), tricuspid valve offset (r=0.583; P=0.004), and tricuspid annular plane systolic excursion (r=0.554; P=0.006). Previously described severity indices ([RA+aRV]/[fRV+LA+LV]) and fRV/LV end-diastolic volume corresponded only to some parameters. In patients with Ebstein anomaly, the easily acquired index of right-sided to left-sided heart volumes from CMR correlated well with established heart failure markers. Our data suggest that the total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity than previously described scoring systems. © 2014 American Heart Association, Inc.

  19. Self regulation initiative to address the heavy vehicle overloading problem in South Africa

    CSIR Research Space (South Africa)

    Nordengen, Paul A

    2004-07-01

    Full Text Available Heavy vehicle overloading continues to be a major problem in South Africa notwithstanding efforts at more effective overload control by the authorities. This paper describes a pilot project, funded by the Department of Trade and Industry...

  20. Development of an overload control strategy for the Republic of Senegal

    CSIR Research Space (South Africa)

    Nordengen, Paul A

    2006-09-01

    Full Text Available traffic in Senegal. An assessment of the commodities transported during the surveys found that cement; sand, steel and general goods are the cargoes that contribute most significantly to overloading of heavy vehicles. The overload control strategy...

  1. Designing a Personalized Guide Recommendation System to Mitigate Information Overload in Museum Learning

    National Research Council Canada - National Science Library

    Yong-Ming Huang; Chien-Hung Liu; Chun-Yi Lee; Yueh-Min Huang

    2012-01-01

    .... However, a problem with information overload has caused in engaging in such learning. Information overload signifies that users encounter a mass of information and need to determine whether certain information needs to be retained...

  2. Fetal liver iron overload: the role of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Cassart, Marie; Avni, Freddy Efraim [Erasme Hospital, Medical imaging, Brussels, Brabant (Belgium); Guibaud, Laurent [Hopital femme mere enfant, Imagerie Pediatrique et Foetale, Lyon-Bron (France); Molho, Marc [C.H.I Poissy/St Germain-en-Laye, Imagerie Medicale, Poissy (France); D' Haene, Nicky [Erasme Hospital, Anatomopathology Department, Brussels (Belgium); Paupe, Alain [C.H.I Poissy/St Germain-en-Laye, Pediatrie, Poissy (France)

    2011-02-15

    To assess the potential role of MR imaging in the diagnosis of fetal liver iron overload. We reviewed seven cases of abnormal liver signal in fetuses referred to MR imaging in a context of suspected congenital infection (n = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with histological data (n = 6) and postnatal work-up (n = 1). Magnetic resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive of iron overload in all cases. The iron overload was confirmed on postnatal biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on US. Magnetic resonance is the only imaging technique able to demonstrate liver iron overload in utero. Yet, the study outlines the fundamental role of MR imaging in cases of congenital haemochromatosis. The antenatal diagnosis of such a condition may prompt ante - (in the case of recurrence) or neonatal treatment, which might improve the prognosis. (orig.)

  3. Iron deficiency and overload in relation to nutrition

    NARCIS (Netherlands)

    Spanjersberg MQI; Jansen EHJM; LEO

    2000-01-01

    Nutritional iron intake in the Netherlands has been reviewed with respect to both iron deficiency and iron overload. In general, iron intake and iron status in the Netherlands are adequate and therefore no change in nutrition policy is required. The following aspects and developments, however, need

  4. Dietary iron rural blacks overload In southern African

    African Journals Online (AJOL)

    1990-09-15

    Sep 15, 1990 ... This finding was ascribed to the fact that traditional brews are not only associated with alcohol- induced hepatic damage but are also a very rich source of ... liver/,J glucose intolerance;4 scurvy and osteoporosis;5 and possibly oesophageal carcinoma.6. There is also evidence to suggest that iron overload ...

  5. Fatigue crack growth due to overloads in plain concrete using ...

    Indian Academy of Sciences (India)

    The predicted results are compared with experimental crack growth data for variable amplitude loading and are found to capture the overload effect with sufficient accuracy. Through a sensitivity analysis, fracture toughness is found to be the most dominant parameter in accelerating the crack length due to application of ...

  6. Dietary iron overload in southern African rural blacks | Friedman ...

    African Journals Online (AJOL)

    A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), 1'-glutamyltransferase (GGn and serological screening ...

  7. Overload prevention in model supports for wind tunnel model testing

    Directory of Open Access Journals (Sweden)

    Anton IVANOVICI

    2015-09-01

    Full Text Available Preventing overloads in wind tunnel model supports is crucial to the integrity of the tested system. Results can only be interpreted as valid if the model support, conventionally called a sting remains sufficiently rigid during testing. Modeling and preliminary calculation can only give an estimate of the sting’s behavior under known forces and moments but sometimes unpredictable, aerodynamically caused model behavior can cause large transient overloads that cannot be taken into account at the sting design phase. To ensure model integrity and data validity an analog fast protection circuit was designed and tested. A post-factum analysis was carried out to optimize the overload detection and a short discussion on aeroelastic phenomena is included to show why such a detector has to be very fast. The last refinement of the concept consists in a fast detector coupled with a slightly slower one to differentiate between transient overloads that decay in time and those that are the result of aeroelastic unwanted phenomena. The decision to stop or continue the test is therefore conservatively taken preserving data and model integrity while allowing normal startup loads and transients to manifest.

  8. Information Overload in Multi-Stage Selection Procedures

    NARCIS (Netherlands)

    S.S. Ficco (Stefano); V.A. Karamychev (Vladimir)

    2004-01-01

    textabstractThe paper studies information processing imperfections in a fully rational decision-making network. It is shown that imperfect information transmission and imperfect information acquisition in a multi-stage selection game yield information overload. The paper analyses the mechanisms

  9. Shift Work, Role Overload, and the Transition to Parenthood

    Science.gov (United States)

    Perry-Jenkins, Maureen; Goldberg, Abbie E.; Pierce, Courtney P.; Sayer, Aline G.

    2007-01-01

    This article examines how the work hours, work schedules, and role overload of working-class couples are related to depressive symptoms and relationship conflict across the transition to parenthood. Data are from 132 dual-earner couples interviewed 5 times across the transition. Multilevel modeling analyses revealed that working evening or night…

  10. Stress 2.0: Social Media Overload among Swiss Teenagers

    NARCIS (Netherlands)

    Lutz, Christoph; Ranzini, Giulia; Meckel, Miriam

    2014-01-01

    Technostress and information overload are serious challenges of the information age. An alarming number of people exhibit dangerously intensive media consumption, while Internet and mobile phone addictions are a widespread phenomenon. At the same time, new media overexposure among young people is

  11. Information Overload and Viral Marketing: Countermeasures and Strategies

    Science.gov (United States)

    Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

    Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

  12. Cardiac nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Gerson, M.C.

    1987-01-01

    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

  13. Determination of Permissible Short-Time Emergency Overloading of Turbo-Generators and Synchronous Compensators

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2011-01-01

    Full Text Available The paper shows that failure to take into account variable ratio of short-time emergency overloading of turbo-generators (synchronous compensators that can lead to underestimation of overloading capacity or impermissible insulation over-heating.A method has been developed for determination of permissible duration of short-time emergency over-loading that takes into account changes of over-loading ratio in case of a failure.

  14. Direct volume estimation without segmentation

    Science.gov (United States)

    Zhen, X.; Wang, Z.; Islam, A.; Bhaduri, M.; Chan, I.; Li, S.

    2015-03-01

    Volume estimation plays an important role in clinical diagnosis. For example, cardiac ventricular volumes including left ventricle (LV) and right ventricle (RV) are important clinical indicators of cardiac functions. Accurate and automatic estimation of the ventricular volumes is essential to the assessment of cardiac functions and diagnosis of heart diseases. Conventional methods are dependent on an intermediate segmentation step which is obtained either manually or automatically. However, manual segmentation is extremely time-consuming, subjective and highly non-reproducible; automatic segmentation is still challenging, computationally expensive, and completely unsolved for the RV. Towards accurate and efficient direct volume estimation, our group has been researching on learning based methods without segmentation by leveraging state-of-the-art machine learning techniques. Our direct estimation methods remove the accessional step of segmentation and can naturally deal with various volume estimation tasks. Moreover, they are extremely flexible to be used for volume estimation of either joint bi-ventricles (LV and RV) or individual LV/RV. We comparatively study the performance of direct methods on cardiac ventricular volume estimation by comparing with segmentation based methods. Experimental results show that direct estimation methods provide more accurate estimation of cardiac ventricular volumes than segmentation based methods. This indicates that direct estimation methods not only provide a convenient and mature clinical tool for cardiac volume estimation but also enables diagnosis of cardiac diseases to be conducted in a more efficient and reliable way.

  15. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  16. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Science.gov (United States)

    2010-07-01

    ... electric equipment and circuits against short circuit and overloads. Three-phase motors on all electric equipment shall be provided with overload protection that will deenergize all three phases in the event that... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and...

  17. A free software for the calculation of T2* values for iron overload assessment.

    Science.gov (United States)

    Fernandes, Juliano Lara; Fioravante, Luciana Andrea Barozi; Verissimo, Monica P; Loggetto, Sandra R

    2017-06-01

    Background Iron overload assessment with magnetic resonance imaging (MRI) using T2* has become a key diagnostic method in the management of many diseases. Quantitative analysis of the MRI images with a cost-effective tool has been a limitation to increased use of the method. Purpose To provide a free software solution for this purpose comparing the results with a commercial solution. Material and Methods The free tool was developed as a standalone program to be directly downloaded and ran in a common personal computer platform without the need of a dedicated workstation. Liver and cardiac T2* values were calculated using both tools and the values obtained compared between them in a group of 56 patients with suspected iron overload using Bland-Altman plots and concordance correlation coefficients (CCC). Results In the heart, the mean T2* differences between the two methods was 0.46 ms (95% confidence interval [CI], -0.037 -0.965) and in the liver 0.49 ms (95% CI, 0.257-0.722). The CCC for both the heart and the liver were significantly high (0.98 [95% CI, 0.966-0.988] with a Pearson ρ of 0.9811 and 0.991 [95% CI, 0.986-0.994] with a Pearson ρ of 0.996, respectively. No significant differences were observed when analyzing only patients with abnormal concentrations of iron in both organs compared to the whole cohort. Conclusion The proposed free software tool is accurate for calculation of T2* values of the liver and heart and might be a solution for centers that cannot use paid commercial solutions.

  18. A novel aldosterone synthase inhibitor ameliorates mortality in pressure-overload mice with heart failure.

    Science.gov (United States)

    Furuzono, Shinji; Meguro, Masaki; Miyauchi, Satoru; Inoue, Shinichi; Homma, Tsuyoshi; Yamada, Keisuke; Tagawa, Yoh-Ichi; Nara, Futoshi; Nagayama, Takahiro

    2017-01-15

    It has been elucidated that mineralocorticoid receptor antagonists reduce mortality in patients with congestive heart failure and post-acute myocardial infarction. A direct inhibition of aldosterone synthase (CYP11B2) is also expected to have therapeutic benefits equal in quality to mineralocorticoid receptor antagonists in terms of reducing mineralocorticoid receptor signaling. Therefore, we have screened our chemical libraries and identified a novel and potent aldosterone synthase inhibitor, 2,2,2-trifluoro-1-{4-[(4-fluorophenyl)amino]pyrimidin-5-y}-1-[1-(methylsulfonyl)piperidin-4-yl]ethanol (compound 1), by lead optimization. Pharmacological properties of compound 1 were examined in in vitro cell-based assays and an in vivo mouse model of pressure-overload hypertrophy by transverse aortic constriction (TAC). Compound 1 showed potent CYP11B2 inhibition against human and mouse enzymes (IC50; 0.003μM and 0.096μM, respectively) in a cell-based assay. The oral administration of 0.06% compound 1 in the food mixture of a mouse TAC model significantly reduced the plasma aldosterone level and ameliorated mortality rate. This study is the first to demonstrate that a CYP11B2 inhibitor improved survival rates of heart failure induced by pressure-overload in mice. The treatment of 0.06% compound 1 did not elevate plasma potassium level in this model, although further evaluation of hyperkalemia is needed. These results suggest that compound 1 can be developed as a promising oral CYP11B2 inhibitor for pharmaceutical applications. Compound 1 could also be a useful compound for clarifying the role of aldosterone in cardiac hypertrophy. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Cardiac sarcoidosis

    Directory of Open Access Journals (Sweden)

    Costello BT

    2016-04-01

    Full Text Available Benedict T Costello,1,2 James Nadel,3 Andrew J Taylor,1,21Department of Cardiovascular Medicine, The Alfred Hospital, 2Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC, 3School of Medicine, University of Notre Dame, Sydney, NSW, Australia Abstract: Cardiac sarcoidosis is a rare but life-threatening condition, requiring a high degree of clinical suspicion and low threshold for investigation to make the diagnosis. The cardiac manifestations include heart failure, conducting system disease, and arrhythmias predisposing to sudden cardiac death. A number of investigations are available to assist in making the diagnosis. The diagnosis may be made from the clinical history and evidence of inflammation on imaging modalities in the active phase and evidence of myocardial scarring in the chronic phase. Keywords: cardiac magnetic resonance, positron emission tomography, sarcoidosis, sudden cardiac death

  20. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    Science.gov (United States)

    Chen, Lijuan; Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2016-05-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. © 2016 The Author(s).

  1. Bi-ventricular finite element model of right ventricle overload in the healthy rat heart.

    Science.gov (United States)

    Masithulela, Fulufhelo

    2016-11-25

    The recognition of RV overpressure is critical to human life, as this may signify morbidity and mortality. Right ventricle (RV) dysfunction is understood to have an impact on the performance of the left ventricle (LV), but the mechanisms remain poorly understood. It is understood that ventricular compliance has the ability to affect cardiac performance. In this study, a bi-ventricular model of the rat heart was used in preference to other, single-ventricle models. Finite element analysis (FEA) of the bi-ventricular model provides important information on the function of the healthy heart. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material using finite element (FE) methods. Bi-ventricular geometries of healthy rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. In simulating the normal passive filling of the rat heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the LV and RV respectively. In addition, to simulate the overpressure of the RV, pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV and RV respectively. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. The results show that the average circumferential stress at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on the endocardium of the over pressured and healthy model respectively. The average circumferential stress at the epicardium, mid-wall and endocardium in the case of a normal heart is 10 times lower than in the overloaded heart model. The finite analysis method is able to provide

  2. Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat

    National Research Council Canada - National Science Library

    Gaborit, B; Kober, F; Jacquier, A; Moro, P J; Cuisset, T; Boullu, S; Dadoun, F; Alessi, M-C; Morange, P; Clément, K; Bernard, M; Dutour, A

    2012-01-01

    To assess epicardial fat volume (EFV), myocardial TG content (MTGC) and metabolic profile in severely obese patients, and to determine whether ectopic fat depots are linked to metabolic disorders or myocardial function...

  3. Stroke volume variation compared with pulse pressure variation and cardiac index changes for prediction of fluid responsiveness in mechanically ventilated patients

    Directory of Open Access Journals (Sweden)

    Randa Aly Soliman

    2015-04-01

    Conclusions: Baseline stroke volume variation ⩾8.15% predicted fluid responsiveness in mechanically ventilated patients with acute circulatory failure. The study also confirmed the ability of pulse pressure variation to predict fluid responsiveness.

  4. Cardiac ablation procedures

    Science.gov (United States)

    Catheter ablation; Radiofrequency catheter ablation; Cryoablation - cardiac ablation; AV nodal reentrant tachycardia - cardiac ablation; AVNRT - cardiac ablation; Wolff-Parkinson-White Syndrome - cardiac ablation; Atrial fibrillation - cardiac ablation; Atrial flutter - ...

  5. Pulse transit time measured by photoplethysmography improves the accuracy of heart rate as a surrogate measure of cardiac output, stroke volume and oxygen uptake in response to graded exercise.

    Science.gov (United States)

    Pollonini, L; Padhye, N S; Re, R; Torricelli, A; Simpson, R J; Dacso, C C

    2015-05-01

    Heart rate (HR) is a valuable and widespread measure for physical training programs, although its description of conditioning is limited to the cardiac response to exercise. More comprehensive measures of exercise adaptation include cardiac output (Q̇), stroke volume (SV) and oxygen uptake (V̇O2), but these physiological parameters can be measured only with cumbersome equipment installed in clinical settings. In this work, we explore the ability of pulse transit time (PTT) to represent a valuable pairing with HR for indirectly estimating Q̇, SV and V̇O2 non-invasively. PTT was measured as the time interval between the peak of the electrocardiographic (ECG) R-wave and the onset of the photoplethysmography (PPG) waveform at the periphery (i.e. fingertip) with a portable sensor. Fifteen healthy young subjects underwent a graded incremental cycling protocol after which HR and PTT were correlated with Q̇, SV and V̇O2 using linear mixed models. The addition of PTT significantly improved the modeling of Q̇, SV and V̇O2 at the individual level ([Formula: see text] for SV, 0.548 for Q̇, and 0.771 for V̇O2) compared to predictive models based solely on HR ([Formula: see text] for SV, 0.503 for Q̇, and 0.745 for V̇O2). While challenges in sensitivity and artifact rejection exist, combining PTT with HR holds potential for development of novel wearable sensors that provide exercise assessment largely superior to HR monitors.

  6. Depletion of cardiac catecholamine stores impairs cardiac norepinephrine re-uptake by downregulation of the norepinephrine transporter.

    Science.gov (United States)

    Kreusser, Michael M; Lehmann, Lorenz H; Haass, Markus; Buss, Sebastian J; Katus, Hugo A; Lossnitzer, Dirk

    2017-01-01

    In heart failure (HF), a disturbed cardiac norepinephrine (NE) homeostasis is characterized by depleted cardiac NE stores, impairment of the cardiac NE re-uptake by the neuronal norepinephrine transporter (NET) and enhanced cardiac NE net release. Reduced cardiac NE content appears to be caused by enhanced cardiac NE net release from sympathetic neurons in HF, triggered by neurohumoral activation. However, it remains unclear whether reduced NE itself has an impact on cardiac NE re-uptake, independent of neurohumoral activation. Here, we evaluated whether depletion of cardiac NE stores alone can regulate cardiac NE re-uptake. Treatment of Wistar rats with reserpine (5 mg/kg/d) for one (1d) or five days (5d) resulted in markedly reduced cardiac NE content, comparable to NE stores in experimental HF due to pressure overload. In order to assess cardiac NE re-uptake, the specific cardiac [3H]-NE uptake via the NET in a Langendorff preparation was measured. Reserpine treatment led to decreased NE re-uptake at 1d and 5d compared to saline treatment. Expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of the NE synthesis, was elevated in left stellate ganglia after reserpine. Mechanistically, measurement of NET mRNA expression in left stellate ganglia and myocardial NET density revealed a post-transcriptional downregulation of the NET by reserpine. In summary, present data demonstrate that depletion of cardiac NE stores alone is sufficient to impair cardiac NE re-uptake via downregulation of the NET, independent of systemic neurohumoral activation. Knowledge about the regulation of the cardiac NE homeostasis may offer novel therapeutic strategies in HF.

  7. microRNA-340-5p Functions Downstream of Cardiotrophin-1 to Regulate Cardiac Eccentric Hypertrophy and Heart Failure via Target Gene Dystrophin.

    Science.gov (United States)

    Zhou, Jian; Gao, Jie; Zhang, Xiaoya; Liu, Yan; Gu, Song; Zhang, Xitao; An, Xiangguang; Yan, Jun; Xin, Yue; Su, Pixiong

    2015-01-01

    Pathological cardiac hypertrophy inevitably leads to the unfavorable outcomes of heart failure (HF) or even sudden death. microRNAs are key regulation factors participating in many pathophysiological processes. Recently, we observed upregulation of microRNA-340-5p (miR-340) in failing human hearts because of dilated cardiomyopathy, but the functional consequence of miR-340 remains to be clarified.We transfected neonatal cardiomyocytes with miR-340 and found fetal gene expression including Nppa, Nppb and Myh7. We also observed eccentric hypertrophy development upon treatment which was analogous to the phenotype after cardiotrophin-1 (CT-1) stimulation. As a potent inducer of cardiac eccentric hypertrophy, treatment by IL-6 family members CT-1 and leukemia inhibitory factor (LIF) led to the elevation of miR-340. Knockdown of miR-340 using antagomir attenuated fetal gene expression and hypertrophy formation, which means miR-340 could convey the hypertrophic signal of CT-1. To demonstrate the initial factor of miR-340 activation, we constructed a volume overloaded abdominal aorta-inferior vena cava fistula rat HF model. miR-340 and CT-1 were found to be up-regulated in the left ventricle. Dystrophin (DMD), a putative target gene of miR-340 which is eccentric hypertrophy-susceptible, was decreased in this HF model upon Western blotting and immunohistochemistry tests. Luciferase assay constructed in two seed sequence of DMD gene 3'UTR showed decreased luciferase activities, and miR-340 transfected cells resulted in the degradation of DMD.miR-340 is a pro-eccentric hypertrophy miRNA, and its expression is dependent on volume overload and cytokine CT-1 activation. Cardiomyocyte structure protein DMD is a target of miR-340.

  8. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia

    National Research Council Canada - National Science Library

    Schmidt, Paul J; Toudjarska, Iva; Sendamarai, Anoop K; Racie, Tim; Milstein, Stuart; Bettencourt, Brian R; Hettinger, Julia; Bumcrot, David; Fleming, Mark D

    2013-01-01

    .... -thalassemia is a congenital anemia caused by partial or complete loss of -globin synthesis causing ineffective erythropoiesis, anemia, decreased hepcidin production, and secondary iron overload...

  9. Epidemiology and Outcomes After In-Hospital Cardiac Arrest After Pediatric Cardiac Surgery

    Science.gov (United States)

    Gupta, Punkaj; Jacobs, Jeffrey P.; Pasquali, Sara K.; Hill, Kevin D.; Gaynor, J. William; O’Brien, Sean M.; He, Max; Sheng, Shubin; Schexnayder, Stephen M.; Berg, Robert A.; Nadkarni, Vinay M.; Imamura, Michiaki; Jacobs, Marshall L.

    2014-01-01

    Background Multicenter data regarding cardiac arrest in children undergoing heart operations are limited. We describe epidemiology and outcomes associated with postoperative cardiac arrest in a large multiinstitutional cohort. Methods Patients younger than 18 years in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2007 through 2012) were included. Patient factors, operative characteristics, and outcomes were described for patients with and without postoperative cardiac arrest. Multivariable models were used to evaluate the association of center volume with cardiac arrest rate and mortality after cardiac arrest, adjusting for patient and procedural factors. Results Of 70,270 patients (97 centers), 1,843 (2.6%) had postoperative cardiac arrest. Younger age, lower weight, and presence of preoperative morbidities (all p cardiac arrest. Arrest rate increased with procedural complexity across common benchmark operations, ranging from 0.7% (ventricular septal defect repair) to 12.7% (Norwood operation). Cardiac arrest was associated with significant mortality risk across procedures, ranging from 15.4% to 62.3% (all p arrest rate was not associated with center volume (odds ratio, 1.06; 95% confidence interval, 0.71 to 1.57 in low- versus high-volume centers). However, mortality after cardiac arrest was higher in low-volume centers (odds ratio, 2.00; 95% confidence interval, 1.52 to 2.63). This association was present for both high- and low-complexity operations. Conclusions Cardiac arrest carries a significant mortality risk across the stratum of procedural complexity. Although arrest rates are not associated with center volume, lower-volume centers have increased mortality after cardiac arrest. Further study of mechanisms to prevent cardiac arrest and to reduce mortality in those with an arrest is warranted. PMID:25443018

  10. Culinary plants and their potential impact on metabolic overload.

    Science.gov (United States)

    Kim, Ji Yeon; Kwon, Oran

    2011-07-01

    Contemporary human behavior has led a large proportion of the population to metabolic overload and obesity. Postprandial hyperlipidemia and hyperglycemia evoke redox imbalance in the short term and lead to complex chronic disease in the long term with repeated occurrence. Complex diseases are best prevented with complex components of plants; thus, current nutrition research has begun to focus on the development of plant-based functional foods and dietary supplements for health and well-being. Furthermore, given the wide range of species, parts, and secondary metabolites, culinary plants can contribute significant variety and complexity to the human diet. Although understanding the health benefits of culinary plants has been one of the great challenges in nutritional science due to their inherent complexity, it is an advantageous pursuit. This review will address the challenges and opportunities relating to studies of the health benefits of culinary plants, with an emphasis on obesity attributed to metabolic overload. © 2011 New York Academy of Sciences.

  11. Early changes in left atrial volume after acute myocardial infarction

    DEFF Research Database (Denmark)

    Bakkestrom, R.; Andersen, Mads J; Ersboll, M.

    2016-01-01

    Background: Dilatation of left atrium (LA) reflects chronic LA pressure or volume overload that possesses considerable prognostic information. Little is known regarding the interaction between LA remodeling after acute myocardial infarction (MI) and left atrial pressure at rest and during exercise...... hypothesis early LA dilatation after MI was weakly associated with resting and exercise induced changes in LA pressure overload. The dilatation was however associated with lower e' and higher MR-proANP. (C) 2016 Elsevier Ireland Ltd. All rights reserved....

  12. Cardiac Rehabilitation

    Science.gov (United States)

    Cardiac rehabilitation (rehab) is a medically supervised program to help people who have A heart attack Angioplasty or coronary artery bypass grafting for coronary heart disease A heart valve repair or replacement A ...

  13. Cardiac rehabilitation

    Science.gov (United States)

    ... ncbi.nlm.nih.gov/pubmed/25503364 . Balady GJ, Williams MA, Ades PA, et al. Core components of ... ncbi.nlm.nih.gov/pubmed/22070836 . Thompson PD. Exercise-based, comprehensive cardiac rehabilitation. In: Mann DL, Zipes ...

  14. Cardiac arrest

    Science.gov (United States)

    ... also run other tests, depending on your health history and the results of these tests. Treatment Cardiac arrest needs emergency treatment right away to get the heart started again. Cardiopulmonary resuscitation (CPR) . This is often the first type of ...

  15. Indecisiveness, Undesirability and Overload Revealed Through Rational Choice Deferral

    OpenAIRE

    Gerasimou, Georgios

    2015-01-01

    Three reasons why decision makers may defer choice are *indecisiveness* between various feasible options, *unattractiveness* of these options, and *choice overload*. This paper provides a choice-theoretic explanation for each of these phenomena by means of three deferral-permitting models of decision making that are driven by preference incompleteness, undesirability and complexity constraints, respectively. These models feature *rational* choice deferral in the sense that whenever the indivi...

  16. Baroreflex function in conscious rats submitted to iron overload

    Directory of Open Access Journals (Sweden)

    L.M. Cardoso

    2005-02-01

    Full Text Available Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12, 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19, a smaller amount of elemental iron was injected (10 mg, daily for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 µg/kg or sodium nitroprusside (1.0 to 10.0 µg/kg. Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold, in contrast to the TIO group (2-fold. Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ± 0.74 and -7.93 ± 1.08 bpm/mmHg, respectively. The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 ± 0.3 sham vs -3.6 ± 0.2 bpm/mmHg 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.

  17. Congenital sideroblastic anemia without clinical iron overload. A case report.

    Science.gov (United States)

    Pignon, J M; Breton-Gorius, J; Bachir, D; Rochant, H

    1990-01-01

    An 18 year old boy presented with microcytic hypochromic anemia. Erythrocytic abnormalities and family studies suggested congenital sideroblastic anemia (CSA), but atypical features included absence of clinical iron overload, scanty iron deposits in mitochondria of late erythroblasts and reticulocytes, and a high platelet count. An unusual adhesion between bone marrow macrophages and reticulocytes was observed by electron microscopy. Haematological response was seen following pyridoxine administration, thus fending support to the diagnosis of CSA.

  18. Cardiac Angiosarcoma

    Directory of Open Access Journals (Sweden)

    Monique Esteves Cardoso

    2011-01-01

    Full Text Available Despite cardiac metastases are found in about 20% of cancer deaths, the presence of primary cardiac tumors is rare. Most primary tumors are benign, and malignant tumors comprise about 15%. We report a 21-year-old man with fever, dyspnea, and hemoptysis that was diagnosed with angiosarcoma of the right atrium and pulmonary metastasis. Patient was submitted to surgical tumor resection without adjuvant therapy and died four months after diagnosis.

  19. Cardiac Angiosarcoma

    OpenAIRE

    Cardoso, Monique Esteves; Canale, Leonardo Secchin; Ramos, Rosana Grandelle; Salvador Junior, Edson da Silva; Lachtermacher, Stephan

    2011-01-01

    Despite cardiac metastases are found in about 20% of cancer deaths, the presence of primary cardiac tumors is rare. Most primary tumors are benign, and malignant tumors comprise about 15%. We report a 21-year-old man with fever, dyspnea, and hemoptysis that was diagnosed with angiosarcoma of the right atrium and pulmonary metastasis. Patient was submitted to surgical tumor resection without adjuvant therapy and died four months after diagnosis.

  20. Cardiac Angiosarcoma

    Science.gov (United States)

    Cardoso, Monique Esteves; Canale, Leonardo Secchin; Ramos, Rosana Grandelle; Salvador Junior, Edson da Silva; Lachtermacher, Stephan

    2011-01-01

    Despite cardiac metastases are found in about 20% of cancer deaths, the presence of primary cardiac tumors is rare. Most primary tumors are benign, and malignant tumors comprise about 15%. We report a 21-year-old man with fever, dyspnea, and hemoptysis that was diagnosed with angiosarcoma of the right atrium and pulmonary metastasis. Patient was submitted to surgical tumor resection without adjuvant therapy and died four months after diagnosis. PMID:24826214

  1. Comparison between noninvasive measurement of central venous pressure using near infrared spectroscopy with an invasive central venous pressure monitoring in cardiac surgical Intensive Care Unit.

    Science.gov (United States)

    Sathish, N; Singh, Naveen G; Nagaraja, P S; Sarala, B M; Prabhushankar, C G; Dhananjaya, Manasa; Manjunatha, N

    2016-01-01

    Central venous pressure (CVP) measurement is essential in the management of certain clinical situations, including cardiac failure, volume overload and sepsis. CVP measurement requires catheterization of the central vein which is invasive and may lead to complications. The aim of this study was to evaluate the accuracy of measurement of CVP using a new noninvasive method based on near infrared spectroscopy (NIRS) in a group of cardiac surgical Intensive Care Unit (ICU) patients. Thirty patients in cardiac surgical ICU were enrolled in the study who had an in situ central venous catheter (CVC). Sixty measurements were recorded in 1 h for each patient. A total of 1800 values were compared between noninvasive CVP (CVPn) obtained from Mespere VENUS 2000 CVP system and invasive CVP (CVPi) obtained from CVC. Strong positive correlation was found between CVPi and CVPn (R = 0.9272, P < 0.0001). Linear regression equation - CVPi = 0.5404 + 0.8875 × CVPn (r2 = 0.86, P < 0.001), Bland-Altman bias plots showed mean difference ± standard deviation and limits of agreement: -0.31 ± 1.36 and - 2.99 to + 2.37 (CVPi-CVPn). Noninvasive assessment of the CVP based on NIRS yields readings consistently close to those measured invasively. CVPn may be a clinically useful substitute for CVPi measurements with an advantage of being simple and continuous. It is a promising tool for early management of acute state wherein knowledge of CVP is helpful.

  2. Formal Constraints on Memory Management for Composite Overloaded Operations

    Directory of Open Access Journals (Sweden)

    Damian W.I. Rouson

    2006-01-01

    Full Text Available The memory management rules for abstract data type calculus presented by Rouson, Morris & Xu [15] are recast as formal statements in the Object Constraint Language (OCL and applied to the design of a thermal energy equation solver. One set of constraints eliminates memory leaks observed in composite overloaded expressions with three current Fortran 95/2003 compilers. A second set of constraints ensures economical memory recycling. The constraints are preconditions, postconditions and invariants on overloaded operators and the objects they receive and return. It is demonstrated that systematic run-time assertion checking inspired by the formal constraints facilitated the pinpointing of an exceptionally hard-to-reproduce compiler bug. It is further demonstrated that the interplay between OCL's modeling capabilities and Fortran's programming capabilities led to a conceptual breakthrough that greatly improved the readability of our code by facilitating operator overloading. The advantages and disadvantages of our memory management rules are discussed in light of other published solutions [11,19]. Finally, it is demonstrated that the run-time assertion checking has a negligible impact on performance.

  3. RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.

    Directory of Open Access Journals (Sweden)

    Xiulian Sun

    Full Text Available Down Syndrome (DS patients develop characteristic Alzheimer's Disease (AD neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1, RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients.

  4. RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.

    Science.gov (United States)

    Sun, Xiulian; Wu, Yili; Herculano, Bruno; Song, Weihong

    2014-01-01

    Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients.

  5. Natural history and information overload: The case of Linnaeus.

    Science.gov (United States)

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-03-01

    Natural History can be seen as a discipline paradigmatically engaged in 'data-driven research.' Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of 'information overload.' Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707-1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called 'natural' system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Acute Effects of Eccentric Overload on Concentric Front Squat Performance.

    Science.gov (United States)

    Munger, Cameron N; Archer, David C; Leyva, Whitney D; Wong, Megan A; Coburn, Jared W; Costa, Pablo B; Brown, Lee E

    2017-05-01

    Munger, CN, Archer, DC, Leyva, WD, Wong, MA, Coburn, JW, Costa, PB, and Brown, LE. Acute effects of eccentric overload on concentric front squat performance. J Strength Cond Res 31(5): 1192-1197, 2017-Eccentric overload is used to enhance performance. The purpose of this study was to investigate the acute effects of eccentric overload on concentric front squat performance. Twenty resistance-trained men (age = 23.80 ± 1.82 years, height = 176.95 ± 5.21 cm, mass = 83.49 ± 10.43 kg, 1 repetition maximum [1RM] front squat = 131.02 ± 21.32 kg) volunteered. A dynamic warm-up and warm-up sets of front squat were performed. Eccentric hooks were added to the barbell. They descended for 3 seconds, until eccentric hooks released, and performed the concentric phase as fast as possible. There were 3 randomly ordered conditions with the concentric phase always at 90% 1RM and the eccentric phase at 105, 110, and 120% of 1RM. Two repetitions were performed for each condition. A repeated measures analysis of variance was used to determine differences. For peak velocity, there were main effects for time and condition (p front squat is a precursor.

  7. Influence, information overload, and information technology in health care.

    Science.gov (United States)

    Rebitzer, James B; Rege, Mari; Shepard, Christopher

    2008-01-01

    We investigate whether information technology (IT) can help physicians more efficiently acquire new knowledge in a clinical environment characterized by information overload. We combine analysis of data from a randomized trial with a theoretical model of the influence that IT has on the acquisition of new medical knowledge. Although the theoretical framework we develop is conventionally microeconomic, the model highlights the non-market and non-pecuniary influence activities that have been emphasized in the sociological literature on technology diffusion. We report three findings. First, empirical evidence and theoretical reasoning suggests that computer-based decision support will speed the diffusion of new medical knowledge when physicians are coping with information overload. Second, spillover effects will likely lead to "underinvestment" in this decision support technology. Third, alternative financing strategies common to new IT, such as the use of marketing dollars to pay for the decision support systems, may lead to undesirable outcomes if physician information overload is sufficiently severe and if there is significant ambiguity in how best to respond to the clinical issues identified by the computer. This is the first paper to analyze empirically and theoretically how computer-based decision support influences the acquisition of new knowledge by physicians.

  8. Determination of left atrial volume in healthy dogs and dogs with myxomatous mitral valve disease

    Directory of Open Access Journals (Sweden)

    Rodrigo P. Franco

    Full Text Available Abstract: The left atrial volume (LAV can be obtained using the biplane Simpson's method via echocardiography. Although in medicine this parameter has been considered to be a prognostic marker of left atrial enlargement in several cardiac diseases, in dogs with myxomatous mitral valve degeneration (MMVD, a valvulopathy characterized by left atrial (LA volume overload, atrial enlargement is usually assessed by the LA-to-Aorta ratio (LA:Ao. Therefore, the body surface area (BSA-indexed LAV was measured in healthy dogs and in dogs with MMVD using the biplane Simpson's method. For this purpose, a total of 107 healthy dogs (control and 81 dogs with MMVD in ACVIM stages B1, B2 and C were assessed, with LAV being calculated during atrial diastole (d and systole (s through the biplane Simpson's method. Two-dimensional apical four-chamber (4C and two-chamber (2C images were obtained in every dog through the left parasternal window. The values obtained from healthy dogs were correlated with body weight using Pearson's test. An analysis of variance (ANOVA and Tukey's test were used to compare healthy and MMVD dogs, as well as to investigate differences according with MMVD stages. A strong positive correlation was documented between either LAVd (r> 0.77 or LAVs (r> 0.73 and body weight in healthy dogs. The BSA-indexed LAV calculated for MMVD dogs was significantly different (p<0.01 from that obtained for the control group. Also, LAV was significantly different (P<0.05 when stages B2 and C, and B1 and C were compared. In conclusion, this study provided a reference for left atrial volume and the applicability of this technique to assess atrial overload in dogs with varying-stage MMVD.

  9. Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Tiziana Angrisano

    Full Text Available Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF. Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ATPase (SERCA-2A and β-myosin-heavy chain (β-MHC genes (Atp2a2 and Myh7, respectively in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC. As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of β-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2 at lysine (K 4 (H3K4me2 and K9 (H3K9me2, H3 trimethylation (me3 at K27 (H3K27me3 and dimethylation (me2 at K36 (H3K36me2. Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2 were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF.

  10. Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure.

    Science.gov (United States)

    Angrisano, Tiziana; Schiattarella, Gabriele Giacomo; Keller, Simona; Pironti, Gianluigi; Florio, Ermanno; Magliulo, Fabio; Bottino, Roberta; Pero, Raffaela; Lembo, Francesca; Avvedimento, Enrico Vittorio; Esposito, Giovanni; Trimarco, Bruno; Chiariotti, Lorenzo; Perrino, Cinzia

    2014-01-01

    Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF). Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ATPase (SERCA-2A) and β-myosin-heavy chain (β-MHC) genes (Atp2a2 and Myh7, respectively) in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC). As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of β-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2) at lysine (K) 4 (H3K4me2) and K9 (H3K9me2), H3 trimethylation (me3) at K27 (H3K27me3) and dimethylation (me2) at K36 (H3K36me2). Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2) were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF.

  11. Performance of new automated transthoracic three-dimensional echocardiographic software for left ventricular volumes and function assessment in routine clinical practice: Comparison with 3 Tesla cardiac magnetic resonance.

    Science.gov (United States)

    Levy, Franck; Dan Schouver, Elie; Iacuzio, Laura; Civaia, Filippo; Rusek, Stephane; Dommerc, Carinne; Marechaux, Sylvestre; Dor, Vincent; Tribouilloy, Christophe; Dreyfus, Gilles

    2017-11-01

    Three-dimensional (3D) transthoracic echocardiography (TTE) is superior to two-dimensional Simpson's method for assessment of left ventricular (LV) volumes and LV ejection fraction (LVEF). Nevertheless, 3D TTE is not incorporated into everyday practice, as current LV chamber quantification software products are time-consuming. To evaluate the feasibility, accuracy and reproducibility of new fully automated fast 3D TTE software (HeartModelA.I.; Philips Healthcare, Andover, MA, USA) for quantification of LV volumes and LVEF in routine practice; to compare the 3D LV volumes and LVEF obtained with a cardiac magnetic resonance (CMR) reference; and to optimize automated default border settings with CMR as reference. Sixty-three consecutive patients, who had comprehensive 3D TTE and CMR examinations within 24hours, were eligible for inclusion. Nine patients (14%) were excluded because of insufficient echogenicity in the 3D TTE. Thus, 54 patients (40 men; mean age 63±13 years) were prospectively included into the study. The inter- and intraobserver reproducibilities of 3D TTE were excellent (coefficient of variation<10%) for end-diastolic volume (EDV), end-systolic volume (ESV) and LVEF. Despite a slight underestimation of EDV using 3D TTE compared with CMR (bias=-22±34mL; P<0.0001), a significant correlation was found between the two measurements (r=0.93; P=0.0001). Enlarging default border detection settings leads to frequent volume overestimation in the general population, but improved agreement with CMR in patients with LVEF≤50%. Correlations between 3D TTE and CMR for ESV and LVEF were excellent (r=0.93 and r=0.91, respectively; P<0.0001). 3D TTE using new-generation fully automated software is a feasible, fast, reproducible and accurate imaging modality for LV volumetric quantification in routine practice. Optimization of border detection settings may increase agreement with CMR for EDV assessment in dilated ventricles. Copyright © 2017 Elsevier Masson SAS

  12. Short-axis epicardial volume change is a measure of cardiac left ventricular short-axis function, which is independent of myocardial wall thickness.

    Science.gov (United States)

    Ugander, Martin; Carlsson, Marcus; Arheden, Håkan

    2010-02-01

    Fractional shortening (FS) by echocardiography is considered to represent the short-axis contribution to the stroke volume (SV), also called short-axis function. However, FS is mathematically coupled to the amount of myocardium, since it rearranges during atrioventricular plane displacement (AVPD). The SV is the sum of the volumes generated by 1) reduction in outer volume of the heart, and 2) inner AVPD. The long-axis contribution to the SV is generated by AVPD, and thus the short-axis contribution is the remaining outer volume change of the heart, which should be unrelated to myocardial wall thickness. We hypothesized that both endocardial and midwall shortening indexed to SV are dependent on myocardial wall thickness, whereas epicardial volume change (EVC) indexed to SV is not. Twelve healthy volunteers (normals), 12 athletes, and 12 patients with dilated cardiomyopathy (ejection fraction EVC was defined as SV minus long-axis function. Endocardial and midwall shortening were measured in a midventricular short-axis slice. Endocardial shortening/SV and midwall shortening/SV both varied in relation to end-diastolic myocardial wall thickness (R(2) = 0.16, P = 0.008 and R(2) = 0.14, P = 0.012, respectively), whereas EVC/SV did not (R(2) = 0.00, P = 0.37). FS is dependent on myocardial wall thickness, whereas EVC is not and therefore represents true short-axis function. This is not surprising considering that FS is mainly caused by rearrangement of myocardium secondary to long-axis function. FS is therefore not synonymous with short-axis function.

  13. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhuo [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013 (China); Wang, Hao; Lin, Marina [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Groban, Leanne, E-mail: lgroban@wakehealth.edu [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Hypertension and Vascular Disease Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Office of Women in Medicine and Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2015-03-27

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.

  14. Real-time three-dimensional echocardiographic left ventricular ejection fraction and volumes assessment: comparison with cardiac computed tomography; Comparacao entre a afericao da fracao de ejecao e dos volumes do ventriculo esquerdo, medidos com ecocardiografia tridimensional em tempo real e com tomografia computadorizada ultra-rapida

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, Marcelo L.C.; Nomura, Cesar H.; Tranchesi Junior, Bernardino; Oliveira, Wercules A. de; Naccarato, Gustavo; Serpa, Bruna S.; Cury, Alexandre; Passos, Rodrigo B.D.; Nobrega, Marcel V. da; Funari, Marcelo B.G.; Pfefermam, Abhaham; Makdisse, Marcia; Fischer, Claudio H.; Morhy, Samira S., E-mail: luiz766@terra.com.br [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil)

    2008-10-15

    Background and objective: Few studies addressed the comparison between real-time 3D echocardiography (RT3DE) and cardiac computed tomography (CCT) concerning left ventricular ejection fraction and volumes assessment. We sought to compare both techniques regarding left ventricle (LV) ejection fraction function and volumes analysis. Methods: we studied by RT3DE (Philips IE 33, And, MA, USA) and by CCT (Toshiba, 64-slice, Otawara, Japan) 41 consecutive patients (29 males, 58 ± 11 yrs). We analysed by both techniques LVEF, LVEDV, LVESV. RT3DE and CCT data were compared by coefficients of determination (r: Pearson), Bland and Altman test and linear regression, 95% CI. Results: RT3DE data: LVEF ranged from 56.7 to 78.9 % (65.3 + 5.7 ); LVEDV ranged from 49.6 to 178.2 (88 + 27.5) mL; LVESV from 11.4 to 78 ( 33.9 + 13.7) mL. CCT data: LVEF ranged from 53 to 86 % (67.3 + 7.9 ); LVEDV ranged from 51 to 186 (106.4 + 30.7) mL; LVESV from 7 to 72 ( 35.1 + 13.8) mL. Correlations relative to RT3DE and CCT were: LVEF (r: 0. 7877, p<0.0001, 95 % CI 0.6327 to 0.8853 ); LVEDV (r:0.7671, p<0.0001, 95 % CI 0.5974 to 0.8745); LVESV (r: 0.8121, p<0.0001, 95 % CI 0.6659 to 0.8957). Conclusions: it was observed adequate correlation between real-time 3D echocardiography and cardiac computed tomography concerning ejection fraction and volumes assessment. (author)

  15. [Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways].

    Science.gov (United States)

    Yao, Jian; Sheng, Hong-zhuan; Lu, Xiao-chen; Gu, Qing-qing; Zhu, Jian-hua

    2013-12-01

    Previous study showed that the signaling pathway of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)- alternative splicing of Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is related to myocardial hypertrophy. The aim of present study was to determine the effect and related mechamism of metoprolol on pressure overload induced myocardial hypertrophy. Pressure overload-induced hypertension was induced by coarctation of suprarenal abdominal aorta in rats. Rats were randomly divided into sham-operated control, hypertension and hypertension plus metoprolol (30 mg×kg(-1)×d(-1)) groups (n = 10 each). Blood pressure, the left ventricular weight to body weight ratio and cardiomyocytes area were measured, the protein expression of Dyrk1A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMKIIδ was detected by RT-PCR. Four weeks after coarctation, cardiac hypertrophy was evidenced in rats of hypertensive group, and the protein expression of Dyrk1A was significantly upregulated, while the expression of ASF was significantly downregulated, the mRNA expression of CaMKIIδ A and B were significantly upregulated and mRNA expression of CaMKIIδ C was significantly downregulated compared to those in sham-operated control rats (all P ASF, and alternative splicing of CaMKIIδ (all P ASF-CaMKIIδ signaling pathways.

  16. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  17. Myocardial iron overload assessed by magnetic resonance imaging (MRI)T2* in multi-transfused patients with thalassemia and acquired anemias.

    Science.gov (United States)

    Fragasso, Alberto; Ciancio, Angela; Mannarella, Clara; Gaudiano, Carlo; Scarciolla, Oronzo; Ottonello, Carlo; Francone, Marco; Nardella, Michele; Peluso, Angelo; Melpignano, Angela; Veglio, Maria Rosaria; Quarta, Giovanni; Turchetti, Cristiano

    2011-02-01

    Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias. To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation. In TM patients cardiac T2* pathologic values (below 20 ms) were found in 37 patients. Serum ferritin was negatively associated with age (r=-0.32, p=0.001) and weakly with T2* values (r=-0.19, p=0.057). A positive correlation was found between T2* and LVEF (r=0.27, p=0.006). Out of 37 patients with T2*<20 ms, 18 (48%) had serum ferritin values<1000 ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399 ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r=-0.53, p=0.07). In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  18. The importance of tricuspid regurgitation and right ventricular overload in ICD/CRT recipients: beside the left, beyond the left.

    Science.gov (United States)

    Fazio, Serafino; Carlomagno, Guido

    2011-10-01

    Device therapy for advanced heart failure has become increasingly employed in the last 10 years. Several retrospective studies have postulated a harmful effect of implantable cardioverter-defibrillator (ICD) lead placement on tricuspid valve function and right heart hemodynamics, in particular among patients with preexisting pulmonary vascular overload and both left and right ventricular remodeling/dysfunction. This functional hypothesis is also supported by long-term clinical follow-up analyses of ICD and cardiac resynchronization therapy recipients. In this viewpoint, we propose that the possibility of worsening tricuspid regurgitation and consequent hemodynamic deterioration following device implantation should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors.  ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

  19. Prediction of the estimated 5-year risk of sudden cardiac death and syncope or non-sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy using late gadolinium enhancement and extracellular volume CMR.

    Science.gov (United States)

    Avanesov, Maxim; Münch, Julia; Weinrich, Julius; Well, Lennart; Säring, Dennis; Stehning, Christian; Tahir, Enver; Bohnen, Sebastian; Radunski, Ulf K; Muellerleile, Kai; Adam, Gerhard; Patten, Monica; Lund, Gunnar

    2017-06-14

    To evaluate the ability of late gadolinium enhancement (LGE) and mapping cardiac magnetic resonance (CMR) including native T1 and global extracellular volume (ECV) to identify hypertrophic cardiomyopathy (HCM) patients at risk for sudden cardiac death (SCD) and to predict syncope or non-sustained ventricular tachycardia (VT). A 1.5-T CMR was performed in 73 HCM patients and 16 controls. LGE size was quantified using the 3SD, 5SD and full width at half maximum (FWHM) method. T1 and ECV maps were generated by a 3(3)5 modified Look-Locker inversion recovery sequence. Receiver-operating curve analysis evaluated the best parameter to identify patients with increased SCD risk ≥4% and patients with syncope or non-sustained VT. Global ECV was the best predictor of SCD risk with an area under the curve (AUC) of 0.83. LGE size was significantly inferior to global ECV with an AUC of 0.68, 0.70 and 0.70 (all P ECV significantly improved the diagnostic accuracy to identify HCM patients with syncope or non-sustained VT. Combined use of the SCD risk score and global ECV has the potential to improve HCM patient selection, benefiting most implantable cardioverter defibrillators. • Global ECV identified the best HCM patients with increased SCD risk. • Global ECV performed equally well compared to a SCD risk score. • Combined use of the SCD risk score and global ECV improved test accuracy. • Combined use potentially improves selection of HCM patients for ICD implantation.

  20. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  1. [Cardiac amyloidosis].

    Science.gov (United States)

    Boussabah, Elhem; Zakhama, Lilia; Ksontini, Iméne; Ibn Elhadj, Zied; Boukhris, Besma; Naffeti, Sana; Thameur, Moez; Ben Youssef, Soraya

    2008-09-01

    PREREQUIS: Amyloidosis is a rare infiltrative disease characterized by multiple clinical features. Various organs are involved and the cardiovascular system is a common target of amyloidosis. Cardiac involvement may occur with or without clinical manifestations and is considered as a major prognostic factor. To analyze the clinical features of cardiac involvement, to review actual knowledgement concerning echocardiographic diagnostic and to evaluate recent advances in treatment of the disease. An electronic search of the relevant literature was carried out using Medline and Pubmed. Keys words used for the final search were amyloidosis, cardiopathy and echocardiography. We considered for analysis reviews, studies and articles between 1990 and 2007. Amyloidosis represents 5 to 10% of non ischemic cardiomyoparhies. Cardiac involvement is the first cause of restrictive cardiomyopathy witch must be evoked in front of every inexplained cardiopathy after the age of forty. The amyloid nature of cardiopathy is suggered if some manifestations were associated as a peripheric neuropathy, a carpal tunnel sydrome and proteinuria > 3g/day. Echocardiography shows dilated atria, a granular sparkling appearance of myocardium, diastolic dysfunction and thickened left ventricle contrasting with a low electric voltage. The proof of amyloidosis is brought by an extra-cardiac biopsy, the indications of endomyocardial biopsy are very limited. The identification of the amyloid nature of cardiopathy has an direct therapeutic implication: it indicates the use of digitalis, calcium channel blockers and beta-blockers. Today the treatment of amyloidosis remains very unsatisfactory especially in the cardiac involvement. An early diagnosis before the cardiac damage may facilitate therapy and improve prognosis.

  2. On TCP-based Session Initiation Protocol (SIP) Server Overload Control

    OpenAIRE

    Shen, Charles; Schulzrinne, Henning

    2010-01-01

    The Session Initiation Protocol (SIP) server overload management has attracted interest since SIP is being widely deployed in the Next Generation Networks (NGN) as a core signaling protocol. Yet all existing SIP overload control work is focused on SIP-over-UDP, despite the fact that TCP is increasingly seen as the more viable choice of SIP transport. This paper answers the following questions: is the existing TCP flow control capable of handling the SIP overload problem? If not, why and how c...

  3. Four Dimensional Cardiac Imaging

    Science.gov (United States)

    Smith, L. D. R.; Quarendon, P.

    1986-05-01

    A system for the production of a four dimensional (moving three dimensional) human epicardial left ventriculogram, modelled and highlighted to show regional wall motion changes, is described. The moving image is derived by fitting a surface to the three dimensional coordinates of coronary artery bifurcations. These are determined by analysis of digitised biplane coronary cineangiograms. This image system not only provides a unique 3-D view of left ventricular activity but might also provide measures of cardiac dynamics such as, stroke volume and velocity of wall movement. The system is not fully automated although operator interaction may be minimised. Further work on vessel tracking systems is required before full automation is possible.

  4. Cardiac MRI in children and adolescents who have undergone surgical repair of right-sided congenital heart disease. Automated left ventricular volumes and function analysis and effects of different manual adjustments

    Energy Technology Data Exchange (ETDEWEB)

    Rompel, O.; Janka, R.; May, M.S.; Lell, M.M.; Uder, M.; Hammon, M. [University Hospital Erlangen (Germany). Dept. of Radiology; Gloeckler, M.; Dittrich, S. [University Hospital Erlangen (Germany). Dept. of Pediatric Cardiology; Cesnjevar, R. [University Hospital Erlangen (Germany). Dept. of Pediatric Cardiac Surgery

    2015-12-15

    To evaluate automated segmentation and the effects of different manual adjustments regarding left ventricular parameter quantification in cardiac magnetic resonance (MR) data on children and adolescents who have undergone surgical repair of right-sided congenital heart disease (CHD). Dedicated software (syngo.via, Siemens AG) was used to automatically segment and/or manually adjust the end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), myocardial mass (MM) and ejection fraction (EF) before/after manual apex/base adjustment (ADJ-step 1) and after manual apex/base/myocardial contour adjustment (ADJ-step 2; reference standard). MR data of 40 patients (13.1 ± 3.1y, 4-17y) with repaired CHD with decreased pulmonary blood flow (CHD-DPBF) were evaluated. Intra- and inter-rater reliability was determined for 10 randomly selected patients. The software correctly detected the left ventricle in 38/40 (95 %) patients. EDV after automated segmentation: 119.1 ± 44.0ml; after ADJ-step 1: 115.8 ± 39.5 ml; after ADJ-step 2: 116.2 ± 39.4 ml. The corresponding results for ESV were 52.0 ± 18.5/49.6 ± 16.9/49.7 ± 16.4 ml; for SV 67.1 ± 28.5/66.2 ± 25.4/66.5 ± 25.5 ml; for EF 55.5 ± 7.3/56.7 ± 6.6/56.7 ± 6.3%; for MM 83.7 ± 35.9/76.2 ± 28.3/74.6 ± 27.2 g. Significant differences were found for ESV/MM/EF comparing the automated segmentation results with these after ADJ-step 1 and ADJ-step 2. No significant differences were found when comparing all results of ADJ-step 1 and ADJ-step 2 or when comparing EDV/SV results. Intra- and inter-rater reliability was excellent. The mean time effort was 63.4 ± 6.9 s for the automated segmentation, 74.2 ± 8.9 s for ADJ-step 1 and 269.5 ± 39.4 s for ADJ-step 2. Automated left ventricular volumes and function analysis in children and adolescents with surgically treated CHD proved to be feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provided

  5. Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients

    Directory of Open Access Journals (Sweden)

    Yunus Kasım Terzi

    2016-12-01

    Full Text Available Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center crosssectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31 was receiving chelation therapy and the second group (group B, n=13 was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3% patients in group A and in only 1 patient (7.7% in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046. In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05. Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

  6. NHE inhibition does not improve Na(+ or Ca(2+ overload during reperfusion: using modeling to illuminate the mechanisms underlying a therapeutic failure.

    Directory of Open Access Journals (Sweden)

    Byron N Roberts

    2011-10-01

    Full Text Available Reperfusion injury results from pathologies of cardiac myocyte physiology that develop when previously ischemic myocardium experiences a restoration of normal perfusion. Events in the development of reperfusion injury begin with the restoration of a proton gradient upon reperfusion, which then allows the sodium-proton exchanger (NHE to increase flux, removing protons from the intracellular space while importing sodium. The resulting sodium overload drives increased reverse-mode sodium-calcium exchanger (NCX activity, creating a secondary calcium overload that has pathologic consequences. One of the attempts to reduce reperfusion-related damage, NHE inhibition, has shown little clinical benefit, and only when NHE inhibitors are given prior to reperfusion. In an effort to further understand why NHE inhibitors have been largely unsuccessful, we employed a new mathematical cardiomyocyte model that we developed for the study of ischemia and reperfusion. Using this model, we simulated 20 minutes of ischemia and 10 minutes of reperfusion, while also simulating NHE inhibition by reducing NHE flux in our model by varying amounts and at different time points. In our simulations, when NHE inhibition is applied at the onset of reperfusion, increasing the degree of inhibition increases the peak sodium and calcium concentrations, as well as reducing intracellular pH recovery. When inhibition was instituted at earlier time points, some modest improvements were seen, largely due to reduced sodium concentrations prior to reperfusion. Analysis of all sodium flux pathways suggests that the sodium-potassium pump (NaK plays the largest role in exacerbated sodium overload during reperfusion, and that reduced NaK flux is largely the result of impaired pH recovery. While NHE inhibition does indeed reduce sodium influx through that exchanger, the resulting prolongation of intracellular acidosis paradoxically increases sodium overload, largely mediated by impaired Na

  7. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

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    Susi Heiden

    Full Text Available BACKGROUND: Endothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure. METHODS: We performed transaortic constriction (TAC in vascular endothelial cells specific ET-1 deficient (VEETKO and wild type (WT mice (n = 5-9 and treated them with pentoxifylline for twelve weeks. RESULTS: TAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax. CONCLUSIONS: Lack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

  8. Stress overload: a new approach to the assessment of stress.

    Science.gov (United States)

    Amirkhan, James H

    2012-03-01

    The link between stress and health has not received strong empirical support, possibly due to problems in the stress measures used. Here, the first wholly empirical development of a new "Stress Overload Scale" is described. A pool of 150 items was formed to reflect "overload", a common denominator in stress theories. Then, the results of five sequenced studies, conducted in heterogeneous community samples, were used to pare the item pool. Exploratory (n = 431) and confirmatory (n = 433) analyses revealed two factors (Event Load and Personal Vulnerability) corresponding to theoretical constructs; only the best factor markers were submitted to further construct validity (n = 310) and reliability tests (n = 342). The 24 strongest items were selected for the SOS, which demonstrated criterion validity in predicting who (n = 285) would become sick following a common stressor. The SOS is (1) psychometrically strong, especially in its validity relative to popular measures; (2) appropriate to community research, due to its brevity and fit to a broad demographic spectrum; (3) unique in its ability to cross-section individuals into risk categories. It should prove useful to community psychologists in determining etiology, diagnosing risk for pathology, and evaluating the efficacy of interventions.

  9. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle.

    Science.gov (United States)

    Khan, Yusra Habib; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Amer Hayat; Mallhi, Tauqeer Hussain

    2016-01-01

    Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

  10. Iron Loading and Overloading due to Ineffective Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Toshihiko Tanno

    2010-01-01

    Full Text Available Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

  11. Immune overload: Parental attitudes toward combination and single antigen vaccines.

    Science.gov (United States)

    Hulsey, Ella; Bland, Tami

    2015-05-21

    Parental concerns have led to a recent decline in immunization coverage, resulting in outbreaks of diseases that were once under control in the US. As the CDC vaccination schedule continues to increase in complexity, the number of required injections per office visit increases as well. Some parents perceive that there is trauma associated with the administration of multiple injections, and research shows that having multiple vaccines due in a single visit is associated with delays and lower immunization rates. Combination vaccines make vaccination more efficient by incorporating the antigens of several different diseases into a single injection, but many parents worry that they may overload the child's developing immune system and leave him or her susceptible to secondary infections. This literature review synthesizes current evidence regarding the parental fear of vaccine-induced immune system overload and the fear of vaccine-associated trauma, in an attempt to understand the scope and nature of these fears. Despite the wealth of knowledge about each of these fears individually, it is still unknown which is of greater concern and how this affects parental decision-making. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Electrochemical sensor for predicting transformer overload by phenol measurement

    Energy Technology Data Exchange (ETDEWEB)

    Bosworth, Timothy; Setford, Steven; Saini, Selwayan [Cranfield Centre for Analytical Science, Cranfield University, Silsoe, Beds MK45 4DT (United Kingdom); Heywood, Richard [National Grid Company Plc, Kelvin Avenue, Leatherhead, Surrey KT22 7ST (United Kingdom)

    2003-03-10

    Transformer overload is a significant problem to the power transmission industry, with severe safety and cost implications. Overload may be predicted by measuring phenol levels in the transformer-insulating oil, arising from the thermolytic degradation of phenol-formaldehyde resins. The development of two polyphenol oxidase (PPO) sensors, based on monitoring the enzymatic consumption of oxygen using an oxygen electrode, or reduction of enzymatically generated o-quinone at a screen-printed electrode (SPE), for the measurement of phenol in transformer oil is reported. Ex-service oils were prepared either by extraction into aqueous electrolyte-buffer, or by direct dilution in propan-2-ol, the latter method being more amenable to simple at-line operation. The oxygen electrode, with a sensitivity of 2.87 nA {mu}g{sup -1} ml{sup -1}, RSD of 7.0-19.9% and accuracy of {+-}8.3% versus the industry standard International Electrotechnical Commission (IEC) method, proved superior to the SPE (sensitivity: 3.02 nA {mu}g{sup -1} ml{sup -1}; RSD: 8.9-18.3%; accuracy: {+-}7.9%) and was considerably more accurate at low phenol concentrations. However, the SPE approach is more amenable to field-based usage for reasons of device simplicity. The method has potential as a rapid and simple screening tool for the at-site monitoring of phenol in transformer oils, thereby reducing incidences of transformer failure.

  13. Criterion validation of a stress measure: the Stress Overload Scale.

    Science.gov (United States)

    Amirkhan, James H; Urizar, Guido G; Clark, Sarah

    2015-09-01

    Validating stress scales poses problems beyond those of other psychological measures. Here, 3 studies were conducted to address those problems and assess the criterion validity of scores from a new theory-derived measure, the Stress Overload Scale (SOS; Amirkhan, 2012). In Study 1, the SOS was tested for its ability to predict postsemester illness in a sample of college students (n = 127). Even with precautions to minimize criterion contamination, scores were found to predict health problems in the month following a final exam on all of 5 different criteria. In Study 2, a community sample (n = 231) was used to test the SOS' ability to differentiate people in stressful circumstances from those in more relaxed contexts. SOS scores demonstrated excellent sensitivity (96%) and specificity (100%) in this general population application. In Study 3, the SOS was tested for its ability to differentiate salivary cortisol responses to a laboratory stressor in a group of pregnant women (n = 40). High scores were found to be associated with a blunted cortisol response, which is indicative of HPA-axis overload and typical of persons suffering chronic stress and stress-related pathology. Across all 3 studies, despite variations in the stressor, criterion, population, and methods, SOS scores emerged as valid indicators of stress. However, each study also introduced new problems that beg additional corrective steps in future stress-scale validity tests. These strategies, and the SOS' utility as a research and diagnostic tool in varied applications and populations, are discussed. (c) 2015 APA, all rights reserved.

  14. Information overload within the health care system: a literature review.

    Science.gov (United States)

    Hall, Amanda; Walton, Graham

    2004-06-01

    There is a widespread view held by health clinicians that their work effectiveness is impaired by 'information overload.' Building upon a previous work by Wilson, a review of the literature was undertaken to look for the evidence of this. It was found that the literature, particularly in the context of the clinical environment, was limited. This review explores the diverse overarching theories of information overload, effects of the phenomenon that are perceived to occur and proposed solutions to this problem. Many of the papers noted an information explosion but only three authors explicitly attempted to measure both the quantity and the complexity of this information. It was also found that the typology of the information studied was severely limited with most studies exploring information such as guidelines, access to journals, research findings and other knowledge intensive areas. Solutions proposed seem to concentrate on technological means rather than exploring the use of humans either in management of information or as a step in the filtering process.

  15. Information overload in healthcare: too much of a good thing?

    Science.gov (United States)

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy. Copyright © 2015. Published by Elsevier GmbH.

  16. Competing for Attention in Social Media under Information Overload Conditions.

    Science.gov (United States)

    Feng, Ling; Hu, Yanqing; Li, Baowen; Stanley, H Eugene; Havlin, Shlomo; Braunstein, Lidia A

    2015-01-01

    Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received.

  17. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  18. Normal cardiac function in mice with supraphysiological cardiac creatine levels

    Science.gov (United States)

    Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A.; Jacobs, Danny O.

    2013-01-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies. PMID:24271489

  19. Benign Cardiac Effects of Hemoglobin H Disease.

    Science.gov (United States)

    Sheeran, Claire; Bowden, Donald K; Pasricha, Sant-Rayn; Cheng, Ken; Romanelli, Giovanni; Peverill, Roger E

    2016-01-01

    Hemoglobin H (HbH) disease is associated with iron overload, but whether this results in serious cardiac or vascular sequelae is unresolved. We identified 39 adult subjects (age 42 ± 12 years, 13 men) with HbH disease who had undergone echocardiography, 27 of whom had also undergone cardiac and liver magnetic resonance assessment of iron loading using T2*-weighted imaging. None of the subjects had a history of heart failure or arrhythmias. There were 13/39 subjects with a ferritin level within the sex-based normal range and only 4/39 had ferritin >1,000 ng/ml. Left ventricular (LV) and left atrial dilatation was common, but LV ejection fraction was normal (≥55%) in all subjects. Age was positively correlated with log ferritin in the 27 nontransfused subjects (r = 0.43) and was inversely correlated with the transmitral E wave and E/A ratio (r = -0.69 and r = -0.79, respectively), but no relation of log ferritin with E or E/A was evident. The peak tricuspid regurgitation velocity was normal in 24/29 subjects for whom this was obtained, and it was no more than mildly elevated in the other 5. None of the tested subjects had an abnormal cardiac T2* reading, but half had evidence of liver iron loading. No myocardial iron loading or serious cardiac or vascular sequelae were identified in this cohort with HbH disease. © 2016 S. Karger AG, Basel.

  20. Tumor necrosis factor receptor-associated factor 3 is a positive regulator of pathological cardiac hypertrophy.

    Science.gov (United States)

    Jiang, Xi; Deng, Ke-Qiong; Luo, Yuxuan; Jiang, Ding-Sheng; Gao, Lu; Zhang, Xiao-Fei; Zhang, Peng; Zhao, Guang-Nian; Zhu, Xueyong; Li, Hongliang

    2015-08-01

    Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process. © 2015 American Heart Association, Inc.

  1. Effects of a Seven Day Overload-Period of High-Intensity Training on Performance and Physiology of Competitive Cyclists

    Science.gov (United States)

    Clark, Bradley; Costa, Vitor P.; O'Brien, Brendan J.; Guglielmo, Luiz G.; Paton, Carl D.

    2014-01-01

    Objectives Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT) on performance and physiological characteristics of competitive cyclists. Design The study was a matched groups, controlled trial. Methods Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO2 peak 4.7±0.5 L·min−1) were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short) or 15, 30 and 45 second (long) maximal intensity efforts. Results Both the short and long HIT regimes led to significant (p0.05) increases (mean ± SD) in VO2 peak (2.3%±4.7% vs 3.5%±6.2%), lactate threshold power (3.6%±3.5% vs 2.9%±5.3%) and gross efficiency (3.2%±2.4% vs 5.1%±3.9%) with only small differences between HIT regimes. Conclusions Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists. PMID:25521824

  2. Effects of a seven day overload-period of high-intensity training on performance and physiology of competitive cyclists.

    Directory of Open Access Journals (Sweden)

    Bradley Clark

    Full Text Available Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT on performance and physiological characteristics of competitive cyclists.The study was a matched groups, controlled trial.Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO2 peak 4.7±0.5 L·min-1 were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short or 15, 30 and 45 second (long maximal intensity efforts.Both the short and long HIT regimes led to significant (p0.05 increases (mean ± SD in VO2 peak (2.3%±4.7% vs 3.5%±6.2%, lactate threshold power (3.6%±3.5% vs 2.9%±5.3% and gross efficiency (3.2%±2.4% vs 5.1%±3.9% with only small differences between HIT regimes.Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists.

  3. Reliability Analysis and Overload Capability Assessment of Oil-Immersed Power Transformers

    Directory of Open Access Journals (Sweden)

    Chen Wang

    2016-01-01

    Full Text Available Smart grids have been constructed so as to guarantee the security and stability of the power grid in recent years. Power transformers are a most vital component in the complicated smart grid network. Any transformer failure can cause damage of the whole power system, within which the failures caused by overloading cannot be ignored. This research gives a new insight into overload capability assessment of transformers. The hot-spot temperature of the winding is the most critical factor in measuring the overload capacity of power transformers. Thus, the hot-spot temperature is calculated to obtain the duration running time of the power transformers under overloading conditions. Then the overloading probability is fitted with the mature and widely accepted Weibull probability density function. To guarantee the accuracy of this fitting, a new objective function is proposed to obtain the desired parameters in the Weibull distributions. In addition, ten different mutation scenarios are adopted in the differential evolutionary algorithm to optimize the parameter in the Weibull distribution. The final comprehensive overload capability of the power transformer is assessed by the duration running time as well as the overloading probability. Compared with the previous studies that take no account of the overloading probability, the assessment results obtained in this research are much more reliable.

  4. "Something's Gotta Give:" Advanced-Degree Seeking Women's Experiences of Sexism, Role Overload, and Psychological Distress

    Science.gov (United States)

    West, Lindsey M.

    2014-01-01

    With the rise in advanced-degree seeking women and the minimal research on the dual impact of sexism and role overload, the current study aims to better understand the impact of sexism and role overload on psychological distress in a particular sample of advanced-degree seeking women. Seventy-six female medical student participants (mean age 24.7)…

  5. Data Overload Impact on Project Management: How Knowledge Management Systems Can Improve Federal Agencies Effectiveness

    Science.gov (United States)

    Rodriguez, Jacinto

    2013-01-01

    This mixed method exploratory case study was used to explore the effect data overload has on project management, how data overload affects project management effectiveness, how prepared program office staff is to manage multiple projects effectively, and how the program office's organizational structure and data management systems affect project…

  6. Designing a Personalized Guide Recommendation System to Mitigate Information Overload in Museum Learning

    Science.gov (United States)

    Huang, Yong-Ming; Liu, Chien-Hung; Lee, Chun-Yi; Huang, Yueh-Min

    2012-01-01

    Museum learning has received a lot of attention in recent years. Museum learning refers to people's use of museums to acquire knowledge. However, a problem with information overload has caused in engaging in such learning. Information overload signifies that users encounter a mass of information and need to determine whether certain information…

  7. Managing Information Overload for Senior Leaders in the 21st Century

    Science.gov (United States)

    Jackson, Jason M.

    2013-01-01

    Information overload is a state where information input exceeds processing capability by an individual, and adverse effects of information overload, such as becoming less productive, making bad decisions, and becoming highly selective, are growing. Guided by Glaser and Strauss' work on grounded theory, this study examined adverse impact of…

  8. Choice overload and the quaterlife phase : Do higher educated quaterlifers experience more stress?

    NARCIS (Netherlands)

    Launspach, T.; Deijl, M. van der; Spiering, M.; Heemskerk, M.M.; Maas, E.N.; Marckelbach, D.

    2016-01-01

    The hypothesis that higher educated twenty-somethings experience more choice overload than lower educated twenty-somethings was tested. 146 participants, either in university or in community college, filled in questionnaires asserting their levels of choice overload. As expected, higher educated

  9. Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation

    NARCIS (Netherlands)

    Paul, Cornelis P. L.; de Graaf, Magda; Bisschop, Arno; Holewijn, Roderick M.; van de Ven, Peter M.; van Royen, Barend J.; Mullender, Margriet G.; Smit, Theodoor H.; Helder, Marco N.

    2017-01-01

    Lumbar hernias occur mostly in the posterolateral region of IVDs and mechanical loading is an important risk factor. Studies show that dynamic and static overloading affect the nucleus and annulus of the IVD differently. We hypothesize there is also variance in the effect of overloading on the IVD's

  10. The Use of Graphs as Decision Aids in Relation to Information Overload and Managerial Decision Quality.

    Science.gov (United States)

    Chan, Siu Y.

    2001-01-01

    Discussion of information overload focuses on a study of masters degree students at a Hong Kong university that investigated the effectiveness of graphs as decision aids to reduce adverse effects of information overload on decision quality. Results of a simulation of a business prediction task with a sample of business managers are presented.…

  11. Designing immersive surgical training against information technology-related overload in the operating room

    NARCIS (Netherlands)

    Pluyter, J.R.

    2012-01-01

    On a theoretical level, this dissertation demonstrates that the “classical” conceptualization of overload in the field of Information Systems being an excessive amount of information is too simplistic. Based on the Emotional-Cognitive Overload Model by Rutkowski and Saunders (2011) this dissertation

  12. Information Overload in the New World of Work: Qualitative Study into the Reasons and Countermeasures

    NARCIS (Netherlands)

    ter Heerdt, Jeroen; Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Guiderdoni-Jourdain, Karine; Oiry, Ewan

    2009-01-01

    In this chapter the authors present a revision of the information overload concept elaborated by Eppler and Mengis (2004). The main elements of our approach are literature synopsis and analysis, qualitative semi-structured interviews, and discussion. Their review of the information overload concept

  13. Spreading the Load: Mobile Information and Communications Technologies and Their Effect on Information Overload

    Science.gov (United States)

    Allen, David K.; Shoard, M.

    2005-01-01

    Introduction: We report on a small-scale research project which examined the impact of mobile technologies on the users' experience of information overload. The project focused on a group of worker who have had relatively little attention in both the mobile technology and information overload literatures: senior managers. Method: The case study…

  14. Learners' Perceived Information Overload in Online Learning via Computer-Mediated Communication

    Science.gov (United States)

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2011-01-01

    Many studies report information overload as one of the main problems that students encounter in online learning via computer-mediated communication. This study aimed to explore the sources of online students' information overload and offer suggestions for increasing students' cognitive resources for learning. Participants were 12 graduate students…

  15. Crack tip strain evolution and crack closure during overload of a growing fatigue crack

    Directory of Open Access Journals (Sweden)

    De-Qiang Wang

    2017-07-01

    Full Text Available It is generally accepted that fatigue crack growth is retarded after an overload, which has been explained either by plasticity-induced crack closure or near-tip residual stress. However, any interpretation of overload effect is insufficient if strain evolution in front of crack tip is not properly considered. The current understanding of overload-induced retardation lacks the clarification of the relationship between crack closure at crack wake and strain evolution at crack tip. In this work, a material with low work hardening coefficient was used to study the effect of overload on crack tip strain evolution and crack closure by in-situ SEM observation and digital image correlation technique. Crack opening displacement (COD and crack tip strain were measured before and after the overload. It was observed that the evolution of crack tip strain follows the crack opening behaviour behind the crack tip, indicating a smaller influence of overload on micro-mechanical behaviour of fatigue crack growth. After the overload, plastic strain accumulation was responsible for crack growth. The strain at a certain distance to crack tip was mapped, and it was found that the crack tip plastic zone size correlated well with crack growth rate during post-overload fatigue crack propagation.

  16. Eccentric overload training in patients with a chronic Achilles tendinopathy: a systematic review.

    NARCIS (Netherlands)

    R. de Knikker; T. Takken; J.J. Kingma; Dr. H.M. Wittink

    2007-01-01

    Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the

  17. Coping with Overload and Stress: Men and Women in Dual-Earner Families

    Science.gov (United States)

    Higgins, Chris A.; Duxbury, Linda E.; Lyons, Sean T.

    2010-01-01

    This study tested gender differences in a model positing relationships between work and family demands, overload, 4 coping mechanisms, and stress. The coping mechanisms were hypothesized to moderate the relationship between overload and stress. The sample consisted of 1,404 men and 1,623 women in dual-earner families. Respondents relied on 2…

  18. Left atrial deformation: Useful index for early detection of cardiac damage in chronic mitral regurgitation.

    Science.gov (United States)

    Cameli, M; Incampo, E; Mondillo, S

    2017-12-01

    In chronic mitral regurgitation (MR) left atrium is one of the first cardiac structures that is involved in remodeling and ultrastructural changes for a progressive volume overload. Severe left atrial (LA) dilation on echocardiography and new onset of atrial fibrillation in asymptomatic patients with preserved Left Ventricular (LV) function, appeared as a Class IIb recommendation for consideration for surgical mitral valve repair in the actual guidelines. However, before atrial dilatation and dysfunction, several ultrastructural changes appear in the atrial muscle tissue that are difficult to identify with the standard echocardiography. Speckle tracking echocardiography (STE) can analyze LA function: it has been showed that it can indirectly identify structural tissue modifications from excessive atrial effort in the early stages of MR up to the full depression of atrial function in the late stages where there are advanced ultrastructural alterations. This review aims to summarize current knowledge on the role of atrial strain identifying early structural alterations of the atrial tissue in the rising stages of MR considering that Left Atrial Peak Longitudinal Strain (PALS) considered useful parameter for a more extensive evaluation of MR patients.

  19. Calcium and magnesium levels in isolated mitochondria from human cardiac biopsies.

    Science.gov (United States)

    Saetersdal, T; Engedal, H; Røli, J; Myklebust, R

    1980-01-01

    A non-enzymatic method is presented for isolating mitochondria from small-sized human cardiac samples, including ventricular needle biopsies of 15-25 mg of wet weight. Electron microscopy demonstrates that these fractions are rich in structurally well preserved mitochondria. Calcium and magnesium levels of fractions are determined by atomic absorption flame spectroscopy. Comparative analyses are made in similar fractions of the mouse ventricle. Calcium concentrations of mitocondria isolated in the presence of ruthenium red do not differ significantly between the human auricle and ventricle, averaging 61 nmol Ca/mg protein and 68 nmol Ca/mg protein, respectively. Mitochondrial calcium level is lower in the mouse ventricular fractions, averaging 7 nmol Ca/mg protein. Mitochondrial magnesium amounts to slightly less than 60% of the calcium levels in the human heart, while it exceeds the calcium level by more than 100 per cent in the mouse heart. There is no significant difference of mitochondrial calcium between normal auricles, and, auricles of patients with increased right atrial mean pressure and/or volume overload.

  20. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    Guenancia, Charles [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Li, Na [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Hachet, Olivier [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Rigal, Eve [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cottin, Yves [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Cardiology Department, University Hospital, Dijon (France); Dutartre, Patrick; Rochette, Luc [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France); Vergely, Catherine, E-mail: cvergely@u-bourgogne.fr [INSERM UMR866, University of Burgundy, LPPCM, Faculties of Medicine and Pharmacy, Dijon (France)

    2015-04-15

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15 mg/kg) for 3 weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6 mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000 μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+ 22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. - Highlights: • The effects of iron on cardiomyocytes were opposite to those on cancer cell lines. • In our model, iron overload did not potentiate anthracycline cardiotoxicity. • Chronic oxidative stress induced by iron could mitigate doxorubicin cardiotoxicity. • The role of iron in

  1. Age of transfused blood is not associated with increased postoperative adverse outcome after cardiac surgery.

    LENUS (Irish Health Repository)

    McKenny, M

    2011-05-01

    This study investigated the hypothesis that storage age of transfused red blood cells (RBCs) is associated with adverse outcome after cardiac surgery, and examined association between volume of RBC transfusions and outcome after cardiac surgery.

  2. Cardiac MRI in Children and Adolescents Who Have Undergone Surgical Repair of Right-Sided Congenital Heart Disease: Automated Left Ventricular Volumes and Function Analysis and Effects of Different Manual Adjustments.

    Science.gov (United States)

    Rompel, O; Janka, R; May, M S; Glöckler, M; Cesnjevar, R; Dittrich, S; Lell, M M; Uder, M; Hammon, M

    2015-12-01

    To evaluate automated segmentation and the effects of different manual adjustments regarding left ventricular parameter quantification in cardiac magnetic resonance (MR) data on children and adolescents who have undergone surgical repair of right-sided congenital heart disease (CHD). Dedicated software (syngo.via, Siemens AG) was used to automatically segment and/or manually adjust the end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), myocardial mass (MM) and ejection fraction (EF) before/after manual apex/base adjustment (ADJ-step 1) and after manual apex/base/myocardial contour adjustment (ADJ-step 2; reference standard). MR data of 40 patients (13.1 ± 3. y, 4 - 17 y) with repaired CHD with decreased pulmonary blood flow (CHD-DPBF) were evaluated. Intra- and inter-rater reliability was determined for 10 randomly selected patients. The software correctly detected the left ventricle in 38/40 (95%) patients. EDV after automated segmentation: 119.1 ± 44.0 ml; after ADJ-step 1: 115.8 ± 9.5 ml; after ADJ-step 2: 116.2 ± 39.4 ml. The corresponding results for ESV were 52.0 ± 18.5/49.6 ± 6.9/49.7 ± 16.4 ml; for SV 67.1 ± 28.5/66.2 ± 25.4/66.5 ± 25. ml; for EF 55.5 ± 7.3/56.7 ± 6.6/56.7 ± 6.3%; for MM 83.7 ± 35.9/76.2 ± 8.3/74.6 ± 27.2 g. Significant differences were found for ESV/MM/EF comparing the automated segmentation results with these after ADJ-step 1 and ADJ-step 2. No significant differences were found when comparing all results of ADJ-step 1 and ADJ-step 2 or when comparing EDV/SV results. Intra- and inter-rater reliability was excellent. The mean time effort was 63.4 ± 6.9 s for the automated segmentation, 74.2 ± 8.9 s for ADJ-step 1 and 269.5 ± 39.4 s for ADJ-step 2. Automated left ventricular volumes and function analysis in children and adolescents with surgically treated CHD proved to be feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provided

  3. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

    Science.gov (United States)

    Ghule, Arvindkumar E; Kandhare, Amit D; Jadhav, Suresh S; Zanwar, Anand A; Bodhankar, Subhash L

    2015-09-01

    Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Cardiac Physiology for Radiologists: Review of Relevant Physiology for Interpretation of Cardiac MR Imaging and CT.

    Science.gov (United States)

    Sheth, Pooja J; Danton, Gary H; Siegel, Yoel; Kardon, Richard E; Infante, Juan C; Ghersin, Eduard; Fishman, Joel E

    2015-01-01

    Cardiac computed tomography (CT) and magnetic resonance (MR) imaging provide clinicians with important insights into cardiac physiology and pathology. However, not all radiologists understand the language and concepts of cardiac physiology that are used daily by cardiologists. This review article covers basic cardiac physiology as it relates to cardiac CT and MR imaging. Topics include a review of the cardiac cycle and left ventricular pressure-volume loops as they relate to different pathologic states, evaluation of cardiac function, and calculation of key parameters such as left ventricular volumes and the ejection fraction. The hemodynamics of cardiac shunts are covered, with an emphasis on factors important to cardiologists, including the ratio of pulmonary flow to systemic flow. Additionally, valvular physiologic function is reexamined, with a focus on understanding pressure gradients within the heart and also the changes associated with valvular pathologic conditions, including measurement of regurgitant fractions in patients with valvular insufficiency. Understanding these basic concepts will help radiologists tailor the reporting of cardiac studies to clinically relevant information. (©)RSNA, 2015.

  5. Biological tissue magnetism in the frame of iron overload diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco J. [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Zaragoza 50009 (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain); Abadia, Ana R. [Departamento de Farmacologia y Fisiologia, Universidad de Zaragoza, Zaragoza 50013 (Spain); Romero, Maria S. [Departamento de Medicina y Psiquiatria, Universidad de Zaragoza, Zaragoza 50009 (Spain); Lopez, A. [CNAM-Salesianos Zaragoza, Zaragoza 50009 (Spain)

    2007-09-15

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest.

  6. Iron overload in the liver diagnostic and quantification

    Energy Technology Data Exchange (ETDEWEB)

    Alustiza, Jose M. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)]. E-mail: jmalustiza@osatek.es; Castiella, Agustin [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Juan, Maria D. de [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Emparanza, Jose I. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Artetxe, Jose [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Uranga, Maite [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)

    2007-03-15

    Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification.

  7. [Excessive fluoride inducing calcium overload and apoptosis of ameloblasts].

    Science.gov (United States)

    Ying, Zhang; Lin, Ma; Jian, Li; Ming, Zhong; Kaiqiang, Zhang; Hefeng, Gu

    2014-12-01

    To study the effect of excessive fluoride on calcium overload and apoptosis in cultured rat ameloblasts in vitro. Logarithmic-phase ameloblasts (HAT-7) were treated with 0, 0.4, 0.8, 1.6, 3.2, and 6.4 mmol · L(-1) sodium fluoride (NaF) solution. Cell activities were detected by using a Cell Counting Kit 8 (CCK-8) assay after 48 h of treatment. The effect of fluoride on cell apoptosis was analyzed by using flow cytometry. Excessive fluoride-induced calcium concentration and calreticulin expression changes in ameloblasts were detected by using laser scanning confocal microscopy, Western blot analysis, and real-time quantitative polymerase chain reaction. NaF inhibited ameloblast activity at 1.6, 3.2, and 6.4 mmol · L(-1) (dose-dependent) after 48 h of induction. The Ca2+ fluorescence intensity of HAT-7 cells incubated with 1.6 and 3.2 mmol · L(-1) NaF was higher than that in the control group. The fluoride-induced early-stage apoptosis of ameloblasts after 48 h of induction and the early-stage apoptosis rate was positively correlated with fluoride concentration. Calreticulin mRNA expression in HAT-7 cells was higher than that in the control group after 48 h of incubation with 0.8, 1.2, and 1.6 mmol · L(-1) NaF. Excessive fluoride-induced calcium overload in ameloblasts and further caused endoplasmic reticulum stress-mediated apoptosis.

  8. Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts.

    Science.gov (United States)

    Zhang, Ying; Zhang, KaiQiang; Ma, Lin; Gu, HeFeng; Li, Jian; Lei, Shuang

    2016-09-01

    The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. High fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. These results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Automated Segmentation of Cardiac Magnetic Resonance Images

    DEFF Research Database (Denmark)

    Stegmann, Mikkel Bille; Nilsson, Jens Chr.; Grønning, Bjørn A.

    2001-01-01

    Magnetic resonance imaging (MRI) has been shown to be an accurate and precise technique to assess cardiac volumes and function in a non-invasive manner and is generally considered to be the current gold-standard for cardiac imaging [1]. Measurement of ventricular volumes, muscle mass and function...... is based on determination of the left-ventricular endocardial and epicardial borders. Since manual border detection is laborious, automated segmentation is highly desirable as a fast, objective and reproducible alternative. Automated segmentation will thus enhance comparability between and within cardiac...... studies and increase accuracy by allowing acquisition of thinner MRI-slices. This abstract demonstrates that statistical models of shape and appearance, namely the deformable models: Active Appearance Models, can successfully segment cardiac MRIs....

  10. Effect of physiological overload on pregnancy in women with mitral regurgitation

    Directory of Open Access Journals (Sweden)

    Vera T. M Borges

    2011-01-01

    Full Text Available OBJECTIVES: to evaluate the structural and functional heart abnormalities in women with mitral regurgitation during pregnancy. INTRODUCTION: Women with mitral regurgitation progress well during pregnancy. However, the effects on the heart of the association between pregnancy and mitral regurgitation are not well established. METHODS: This is a case-control, longitudinal prospective study. Echocardiograms were performed in 18 women with mitral regurgitation at the 12th and 36th week of pregnancy and on the 45th day of the puerperium. Twelve age-matched healthy and pregnant women were included as controls and underwent the same evaluation as the study group. RESULTS: Compared with controls, women with mitral regurgitation presented increased left cardiac chambers in all evaluations. Increasing left atrium during pregnancy occurred only in the mitral regurgitation group. At the end of the puerperium, women with mitral regurgitation showed persistent enlargement of the left atrium compared with the beginning of pregnancy (5.0 ± 1.1 cm vs 4.6 ± 0.9 cm; p<0.05. Reduced left ventricular relative wall thickness (0.13 ± 0.02 vs 0.16 ± 0.02; p<0.05 and an increased peak of afterload (278 ± 55 g/cm² vs 207 ± 28 g/cm²;p<0.05 was still observed on the 45th day after delivery in the mitral regurgitation group compared with controls. CONCLUSIONS: Pregnancy causes unfavorable structural alterations in women with mitral regurgitation that are associated with an aggravation of the hemodynamic overload.

  11. Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via suppressing oxidative stress and inflammation: Possible role of silent information regulator 1.

    Science.gov (United States)

    Feng, Jun; Li, Shusheng; Chen, Huawen

    2016-11-15

    Tanshinone IIA (Tan) exerts potential protective effects against cardiovascular diseases. Oxidative stress and inflammation are involved in cardiac hypertrophy. Activation of silent information regulator 1 (SIRT1) signaling has been suggested to attenuate cardiac hypertrophy. This study aims to evaluate the antioxidative and anti-inflammatory effects of Tan treatment in pressure overload-induced myocardial remodeling and elucidated its potential mechanisms. Sprague-Dawley rats were treated with Tan in the absence or presence of the SIRT1 inhibitor sirtinol (Snl) and then subjected to transverse aortic constriction (TAC). Tan conferred cardioprotective effects by improving cardiac function, reducing apoptosis and myocardial remodeling, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Snl attenuated these effects by inhibiting SIRT1 signaling. Tan treatment also reduced myocardium malondialdehyde (MDA) content, and cardiac inflammatory cytokines (TNF-α and IL-6) and increased myocardium superoxide dismutase (SOD) level. However, these effects were also abolished by Snl. In conclusion, these results indicate that Tan significantly attenuates TAC-induced myocardial remodeling possibly due to its strong anti-oxidative and anti-inflammatory activity. Importantly, SIRT1 signaling activation is involved in this process. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Cardiac conduction system

    Science.gov (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals to the ... contract. The main components of the cardiac conduction system are the SA node, AV node, bundle of ...

  13. Sudden Cardiac Arrest (SCA)

    Science.gov (United States)

    ... Arrest (SCA) Back to Heart Diseases & Disorders Sudden Cardiac Arrest (SCA) Sudden Cardiac Arrest ( SCA ) occurs when the heart stops beating, abruptly ... to saving someone who is having a sudden cardiac arrest , it is important to understand the difference. The ...

  14. Alteration of LV end-diastolic volume by controlling the power of the continuous-flow LVAD, so it is synchronized with cardiac beat: development of a native heart load control system (NHLCS).

    Science.gov (United States)

    Umeki, Akihide; Nishimura, Takashi; Ando, Masahiko; Takewa, Yoshiaki; Yamazaki, Kenji; Kyo, Shunei; Ono, Minoru; Tsukiya, Tomonori; Mizuno, Toshihide; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2012-06-01

    There are many reports comparing pulsatile and continuous-flow left ventricular assist devices (LVAD). But continuous-flow LVAD with the pulsatile driving technique had not been tried or discussed before our group's report. We have previously developed and introduced a power-control unit for a centrifugal LVAD (EVAHEART®; Sun Medical), which can change the speed of rotation so it is synchronized with the heart beat. By use of this unit we analyzed the end-diastolic volume (EDV) to determine whether it is possible to change the native heart load. We studied 5 goats with normal hearts and 5 goats with acute LV dysfunction because of micro-embolization of the coronary artery. We used 4 modes, "circuit-clamp", "continuous", "counter-pulse", and "co-pulse", with the bypass rate (BR) 100%. We raised the speed of rotation of the LVAD in the diastolic phase with the counter-pulse mode, and raised it in the systolic phase with the co-pulse mode. As a result, the EDV decreased in the counter-pulse mode and increased in the co-pulse mode, compared with the continuous mode (p < 0.05), in both the normal and acute-heart-failure models. This result means it may be possible to achieve favorable EDV and native heart load by controlling the rotation of continuous-flow LVAD, so it is synchronized with the cardiac beat. This novel driving system may be of great benefit to patients with end-stage heart failure, especially those with ischemic etiology.

  15. Transfusion-associated circulatory overload: A survey among Dutch intensive care fellows.

    Science.gov (United States)

    Klanderman, R B; Attaye, I; Bosboom, J J; Veelo, D P; Geerts, B F; Vlaar, A P J

    2017-12-06

    Transfusion-associated circulatory overload (TACO) is a severe pulmonary transfusion reaction and leading cause of transfusion-related morbidity and mortality in Europe. TACO is of particular importance in critically ill patients, since they often receive blood transfusions and have multiple risk factors for TACO. This study investigates transfusion practices in patients at risk of developing TACO, and furthermore knowledge concerning risk factors, diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows. An unannounced paper-based survey was conducted among Dutch ICU fellows during an educational conference. The survey consisted of 16 multiple and open choice questions. Of all 65 Dutch ICU fellows 56.8% completed the survey; of respondents 88.9% identified the correct constellation of symptoms for TACO. In total, 29.7% of the respondents are aware they are obligated to report TACO cases to the blood bank. Major risk factors for TACO that respondents identified were reduced left ventricular function, infusion volume and infusion rate. In a non-emergency setting, 45.9% of fellows start red blood cell transfusion with 2 units or more. Transfusion rates exceeded national guidelines in 15.4% of fictitious cases. TACO is treated with furosemide by 94.5% of the fellows, however goals of the therapy varied greatly. Dutch ICU fellows are knowledgeable of TACO symptoms, risk factors and treatment, however knowledge on reporting and transfusion practice in the setting of at risk patients for TACO should be improved. Copyright © 2017. Published by Elsevier SAS.

  16. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ... protection against overload which does not conform to the provisions of the National Electric Code, 1968... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and...-UNDERGROUND COAL MINES Electrical Equipment-General § 75.518-1 Electric equipment and circuits; overload and...

  17. Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice.

    Science.gov (United States)

    Guenancia, Charles; Li, Na; Hachet, Olivier; Rigal, Eve; Cottin, Yves; Dutartre, Patrick; Rochette, Luc; Vergely, Catherine

    2015-04-15

    Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran-iron (125-1000μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Contribution of the late sodium current to intracellular sodium and calcium overload in rabbit ventricular myocytes treated by anemone toxin.

    Science.gov (United States)

    Kornyeyev, Dmytro; El-Bizri, Nesrine; Hirakawa, Ryoko; Nguyen, Steven; Viatchenko-Karpinski, Serge; Yao, Lina; Rajamani, Sridharan; Belardinelli, Luiz

    2016-02-01

    Pathological enhancement of late Na(+) current (INa) can potentially modify intracellular ion homeostasis and contribute to cardiac dysfunction. We tested the hypothesis that modulation of late INa can be a source of intracellular Na(+) ([Na(+)]i) overload. Late INa was enhanced by exposing rabbit ventricular myocytes to Anemonia sulcata toxin II (ATX-II) and measured using whole cell patch-clamp technique. [Na(+)]i was determined with fluorescent dye Asante NaTRIUM Green-2 AM. Pacing-induced changes in the dye fluorescence measured at 37°C were more pronounced in ATX-II-treated cells than in control (dye washout prevented calibration). At 22-24°C, resting [Na(+)]i was 6.6 ± 0.8 mM. Treatment with 5 nM ATX-II increased late INa 8.7-fold. [Na(+)]i measured after 2 min of electrical stimulation (1 Hz) was 10.8 ± 1.5 mM and 22.1 ± 1.6 mM (P < 0.001) in the absence and presence of 5 nM ATX-II, respectively. Inhibition of late INa with GS-967 (1 μM) prevented Na(+) i accumulation. A strong positive correlation was observed between the late INa and the pacing-induced increase of [Na(+)]i (R(2) = 0.88) and between the rise in [Na(+)]i and the increases in cytosolic Ca(2+) (R(2) = 0.96). ATX-II, tetrodotoxin, or GS-967 did not affect [Na(+)]i in quiescent myocytes suggesting that late INa was solely responsible for triggering the ATX-II effect on [Na(+)]i. Experiments with pinacidil and E4031 indicate that prolongation of the action potential contributes to as much as 50% of the [Na(+)]i overload associated with the increase in late INa caused by ATX-II. Enhancement of late INa can cause intracellular Na(+) overload in ventricular myocytes. Copyright © 2016 the American Physiological Society.

  19. Impaired cardiac contractility response to hemodynamic stress in S100A1-deficient mice.

    Science.gov (United States)

    Du, Xiao-Jun; Cole, Timothy J; Tenis, Nora; Gao, Xiao-Ming; Köntgen, Frank; Kemp, Bruce E; Heierhorst, Jörg

    2002-04-01

    Ca(2+) signaling plays a central role in cardiac contractility and adaptation to increased hemodynamic demand. We have generated mice with a targeted deletion of the S100A1 gene coding for the major cardiac isoform of the large multigenic S100 family of EF hand Ca(2+)-binding proteins. S100A1(-/-) mice have normal cardiac function under baseline conditions but have significantly reduced contraction rate and relaxation rate responses to beta-adrenergic stimulation that are associated with a reduced Ca(2+) sensitivity. In S100A1(-/-) mice, basal left-ventricular contractility deteriorated following 3-week pressure overload by thoracic aorta constriction despite a normal adaptive hypertrophy. Surprisingly, heterozygotes also had an impaired response to acute beta-adrenergic stimulation but maintained normal contractility in response to chronic pressure overload that coincided with S100A1 upregulation to wild-type levels. In contrast to other genetic models with impaired cardiac contractility, loss of S100A1 did not lead to cardiac hypertrophy or dilation in aged mice. The data demonstrate that high S100A1 protein levels are essential for the cardiac reserve and adaptation to acute and chronic hemodynamic stress in vivo.

  20. Study of overload effects in bainitic steel by synchrotron X-ray diffraction

    Directory of Open Access Journals (Sweden)

    P. Lopez-Crespo

    2013-07-01

    Full Text Available This work presents an in-situ characterisation of crack-tip strain fields following an overload by means of synchrotron X-ray diffraction. The study is made on very fine grained bainitic steel, thus allowing a very high resolution so that small changes occurring around the crack-tip were captured along the crack plane at the mid-thickness of the specimen. We have followed the crack as it grew through the overload location. Once the crack-tip has progressed past the overload event there is strong evidence that the crack faces contact in the region of the overload event (though not in the immediate vicinity of the current locations of the crack tip at Kmin even when the crack has travelled 1mm beyond the overload location. It was also found that at Kmax the peak tensile strain ahead of the crack-tip decreases soon after the overload is applied and then gradually recovers as the crack grows past the compressive region created by the overload.

  1. Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy

    Science.gov (United States)

    Li, Ran; Bai, Jian; Ding, Liang; Gu, Rong; Wang, Lian; Xu, Biao

    2016-01-01

    Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure. PMID:26914935

  2. Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy.

    Science.gov (United States)

    Li, Qiaoling; Xie, Jun; Wang, Bingjian; Li, Ran; Bai, Jian; Ding, Liang; Gu, Rong; Wang, Lian; Xu, Biao

    2016-01-01

    Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure.

  3. What Causes Sudden Cardiac Arrest?

    Science.gov (United States)

    ... Back To Health Topics / Sudden Cardiac Arrest Sudden Cardiac Arrest Also known as Cardiac Arrest , Sudden Cardiac Death ... the condition For People Who Have Survived Sudden Cardiac Arrest If you've already had SCA, you're ...

  4. What Is Sudden Cardiac Arrest?

    Science.gov (United States)

    ... Back To Health Topics / Sudden Cardiac Arrest Sudden Cardiac Arrest Also known as Cardiac Arrest , Sudden Cardiac Death ... the condition For People Who Have Survived Sudden Cardiac Arrest If you've already had SCA, you're ...

  5. Modulation of overload-induced inflammation by aging and anabolic steroid administration.

    Science.gov (United States)

    Thompson, Raymond W; McClung, Joseph M; Baltgalvis, Kristen A; Davis, J Mark; Carson, James A

    2006-11-01

    Aging can alter the skeletal muscle growth response induced by overload. The initiation of overload induces muscle extracellular matrix expansion, increased cellularity, and inflammatory gene expression, which are all related to processes important for myofiber growth. These remodeling processes are also biological targets of testosterone. It is not certain how aging affects the inflammatory response to functional overload and whether anabolic steroid administration can alter this response. The effect of anabolic steroid administration on inflammatory processes during functional overload is not known. The purpose of this study was to determine if age altered the skeletal muscle inflammatory response at the onset of functional overload and whether anabolic steroid administration would modulate this response in young or older animals. Five-month and 25 month F344 x BRN rats were given nandrolone decanoate (ND) (6 mg/kg bw/wk) or sham injections for 3 weeks, and then the soleus muscle was overloaded (OV) for 3 days by synergist ablation. ND alone induced a 230% increase in ED1(+) cells in 5 month muscle. Three days of OV had no effect on ED1(+) cell number at either age. OV combined with ND induced a 90% increase in ED2(+) cells in 5 month muscle, while there was no effect of either treatment alone at this age. In 25 month muscle, OV induced a 40% increase in ED2(+) cells. Regardless of age, OV induced muscle TNF-alpha mRNA expression (300%) and IL-6 mRNA expression (900%). ND attenuated OV-induced IL-6 mRNA but not TNF-alpha expression in both age groups. The overload induction of IL-1beta mRNA was 3-fold greater in 25 month muscle (1400%), compared to 5 month muscle (400%). ND administration ablated the overload IL-1beta mRNA induction in 25 month muscle. Anabolic steroid administration can suppress inflammatory cytokine gene expression at the onset of overload and this effect is age dependent.

  6. Deferasirox for managing iron overload in people with thalassaemia.

    Science.gov (United States)

    Bollig, Claudia; Schell, Lisa K; Rücker, Gerta; Allert, Roman; Motschall, Edith; Niemeyer, Charlotte M; Bassler, Dirk; Meerpohl, Joerg J

    2017-08-15

    Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.We also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015. Randomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment. Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. Sixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.The two studies (a pharmacokinetic and a dose-escalation study

  7. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Krag, A; Bendtsen, F; Møller, S

    2010-01-01

    compared to those with a higher CI (N = 16), padvanced cirrhosis and ascites seem to be related to a cardiac......OBJECTIVES: Recent studies suggest that cardiac dysfunction precedes development of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the relation between cardiac and renal function in patients with cirrhosis and ascites and the impact of cardiac systolic function...... on survival. Patients and DESIGN: Twenty-four patients with cirrhosis and ascites were included. Cardiac function was investigated by gated myocardial perfusion imaging (MPI) for assessment of cardiac index (CI) and cardiac volumes. The renal function was assessed by determination of glomerular filtration...

  8. Information overload an international challenge to professional engineers and technical communicators

    CERN Document Server

    Ulijn, J M; Fazal, Zohra

    2012-01-01

    "This book covers the ever-increasing problem of information overload from both the professional and academic perspectives. Focusing on the needs of practicing engineers and professional communicators, it addresses the causes and costs of information overload, along with strategies and techniques for reducing and minimizing its negative effects. The theoretical framework of information overload and ideas for future research are also presented. The book brings together an international group of authors, providing a truly global point of view on this important, rarely covered topic"--

  9. T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies.

    Science.gov (United States)

    Roller, F C; Harth, S; Schneider, C; Krombach, G A

    2015-09-01

    Cardiac magnetic resonance imaging (CMRI) is a versatile diagnostic tool. One of its main advantages is the possibility of tissue characterization. T1-weighted images for scar and T2-weighted images for edema visualization are key methods for tissue characterization. Otherwise these sequences are strongly limited for the detection of diffuse myocardial pathologies. Recently, rapid technical innovations have generated new techniques. T1, T2 mapping and evaluation of the extracellular volume fraction (ECV) allow quantification of diffuse myocardial pathologies and showed great potential in the visualization of fibrosis, edema, amyloid, iron overload and lipid. In the future these techniques might enable the detection of early cardiac involvement, even act as a prognosticator. Moreover, therapy monitoring and follow-up might be possible due to versatile parameter quantification with these new techniques. CMR allows for tissue characterization via T1- and T2-weighted sequences. In cases of diffuse, global myocardial pathologies, correct image interpretation with traditional CMR sequences might be difficult. T1, T2 mapping and ECV can quantify diffuse, global myocardial pathologies. Alterations of myocardial T1 and T2 relaxation times occur in various myocardial diseases (e.g. acute myocarditis). In the future mapping might act as a prognosticator or therapy monitoring tool. © Georg Thieme Verlag KG Stuttgart · New York.

  10. A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

    Directory of Open Access Journals (Sweden)

    Fábio Henrique Silva

    Full Text Available Patients with heart failure (HF display erectile dysfunction (ED. However, the pathophysiology of ED during HF remains poorly investigated.This study aimed to characterize the aortocaval fistula (ACF rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO pathway, autonomic nervous system and oxidative stress in the penis.Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine and relaxant agents (sodium nitroprusside; SNP, as well as to electrical field stimulation (EFS, were obtained in the cavernosal smooth muscle (CSM strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS and neuronal NO synthase (nNOS and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox and superoxide dismutase (SOD mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs were also performed in plasma.HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats.ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.

  11. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

    OpenAIRE

    Shaqura, Mohammed; Mohamed, Doaa M.; Aboryag, Noureddin B.; Bedewi, Lama; Dehe, Lukas; Treskatsch, Sascha; Shakibaei, Mehdi; Schaefer, Michael; Mousa, Shaaban A

    2017-01-01

    Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for th...

  12. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats.

    Directory of Open Access Journals (Sweden)

    Mohammed Shaqura

    Full Text Available Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

  13. Histopathological Changes in the Kidney following Congestive Heart Failure by Volume Overload in Rats

    Directory of Open Access Journals (Sweden)

    Noureddin B. Aboryag

    2017-01-01

    Full Text Available Background. This study investigated histopathological changes and apoptotic factors that may be involved in the renal damage caused by congestive heart failure in a rat model of infrarenal aortocaval fistula (ACF. Methods. Heart failure was induced using a modified approach of ACF in male Wistar rats. Sham-operated controls and ACF rats were characterized by their morphometric and hemodynamic parameters and investigated for their histopathological, ultrastructural, and apoptotic factor changes in the kidney. Results. ACF-induced heart failure is associated with histopathological signs of congestion and glomerular and tubular atrophy, as well as nuclear and cellular degeneration in the kidney. In parallel, overexpression of proapoptotic Bax protein, release of cytochrome C from the outer mitochondrial membrane into cell cytoplasm, and nuclear transfer of activated caspase 3 indicate apoptotic events. This was confirmed by electron microscopic findings of apoptotic signs in the kidney such as swollen mitochondria and degenerated nuclei in renal tubular cells. Conclusions. This study provides morphological evidence of renal injury during heart failure which may be due to caspase-mediated apoptosis via overexpression of proapoptotic Bax protein, subsequent mitochondrial cytochrome C release, and final nuclear transfer of activated caspase 3, supporting the notion of a cardiorenal syndrome.

  14. Cardiac differentiation of cardiosphere-derived cells in scaffolds mimicking morphology of the cardiac extracellular matrix.

    Science.gov (United States)

    Xu, Yanyi; Patnaik, Sourav; Guo, Xiaolei; Li, Zhenqing; Lo, Wilson; Butler, Ryan; Claude, Andrew; Liu, Zhenguo; Zhang, Ge; Liao, Jun; Anderson, Peter M; Guan, Jianjun

    2014-08-01

    Stem cell therapy has the potential to regenerate heart tissue after myocardial infarction (MI). The regeneration is dependent upon cardiac differentiation of the delivered stem cells. We hypothesized that timing of the stem cell delivery determines the extent of cardiac differentiation as cell differentiation is dependent on matrix properties such as biomechanics, structure and morphology, and these properties in cardiac extracellular matrix (ECM) continuously vary with time after MI. In order to elucidate the relationship between ECM properties and cardiac differentiation, we created an in vitro model based on ECM-mimicking fibers and a type of cardiac progenitor cell, cardiosphere-derived cells (CDCs). A simultaneous fiber electrospinning and cell electrospraying technique was utilized to fabricate constructs. By blending a highly soft hydrogel with a relatively stiff polyurethane and modulating fabrication parameters, tissue constructs with similar cell adhesion property but different global modulus, single fiber modulus, fiber density and fiber alignment were achieved. The CDCs remained alive within the constructs during a 1week culture period. CDC cardiac differentiation was dependent on the scaffold modulus, fiber volume fraction and fiber alignment. Two constructs with relatively low scaffold modulus, ∼50-60kPa, most significantly directed the CDC differentiation into mature cardiomyocytes as evidenced by gene expressions of cardiac troponin T (cTnT), calcium channel (CACNA1c) and cardiac myosin heavy chain (MYH6), and protein expressions of cardiac troponin I (cTnI) and connexin 43 (CX43). Of these two low-modulus constructs, the extent of differentiation was greater for lower fiber alignment and higher fiber volume fraction. These results suggest that cardiac ECM properties may have an effect on cardiac differentiation of delivered stem cells. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Aberrant Splicing Promotes Proteasomal Degradation of L-type Ca v 1.2 Calcium Channels by Competitive Binding for CaV β Subunits in Cardiac Hypertrophy

    NARCIS (Netherlands)

    Hu, Zhenyu; Wang, Jiong Wei; Yu, Dejie; Soon, Jia Lin; De Kleijn, Dominique P V|info:eu-repo/dai/nl/30481489X; Foo, Roger; Liao, Ping; Colecraft, Henry M.; Soong, Tuck Wah

    2016-01-01

    Decreased expression and activity of Ca V1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of Ca V1.2 channel, named Ca V1.2 e21+22, that

  16. About Cardiac Arrest

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Cardiac Arrest Updated:Mar 10,2017 What is cardiac arrest? ... and procedures related to heart disease and stroke. Cardiac Arrest • Home • About Cardiac Arrest • Understand Your Risk for ...

  17. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with

  18. Reduced cardiac fructose 2,6 bisphosphate increases hypertrophy and decreases glycolysis following aortic constriction.

    Science.gov (United States)

    Wang, Jianxun; Xu, Jianxiang; Wang, Qianwen; Brainard, Robert E; Watson, Lewis J; Jones, Steven P; Epstein, Paul N

    2013-01-01

    This study was designed to test whether reduced levels of cardiac fructose-2,6-bisphosphate (F-2,6-P(2)) exacerbates cardiac damage in response to pressure overload. F-2,6-P(2) is a positive regulator of the glycolytic enzyme phosphofructokinase. Normal and Mb transgenic mice were subject to transverse aortic constriction (TAC) or sham surgery. Mb transgenic mice have reduced F-2,6-P(2) levels, due to cardiac expression of a transgene for a mutant, kinase deficient form of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) which controls the level of F-2,6-P(2). Thirteen weeks following TAC surgery, glycolysis was elevated in FVB, but not in Mb, hearts. Mb hearts were markedly more sensitive to TAC induced damage. Echocardiography revealed lower fractional shortening in Mb-TAC mice as well as larger left ventricular end diastolic and end systolic diameters. Cardiac hypertrophy and pulmonary congestion were more severe in Mb-TAC mice as indicated by the ratios of heart and lung weight to tibia length. Expression of α-MHC RNA was reduced more in Mb-TAC hearts than in FVB-TAC hearts. TAC produced a much greater increase in fibrosis of Mb hearts and this was accompanied by 5-fold more collagen 1 RNA expression in Mb-TAC versus FVB-TAC hearts. Mb-TAC hearts had the lowest phosphocreatine to ATP ratio and the most oxidative stress as indicated by higher cardiac content of 4-hydroxynonenal protein adducts. These results indicate that the heart's capacity to increase F-2,6-P(2) during pressure overload elevates glycolysis which is beneficial for reducing pressure overload induced cardiac hypertrophy, dysfunction and fibrosis.

  19. Reduced cardiac fructose 2,6 bisphosphate increases hypertrophy and decreases glycolysis following aortic constriction.

    Directory of Open Access Journals (Sweden)

    Jianxun Wang

    Full Text Available This study was designed to test whether reduced levels of cardiac fructose-2,6-bisphosphate (F-2,6-P(2 exacerbates cardiac damage in response to pressure overload. F-2,6-P(2 is a positive regulator of the glycolytic enzyme phosphofructokinase. Normal and Mb transgenic mice were subject to transverse aortic constriction (TAC or sham surgery. Mb transgenic mice have reduced F-2,6-P(2 levels, due to cardiac expression of a transgene for a mutant, kinase deficient form of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2 which controls the level of F-2,6-P(2. Thirteen weeks following TAC surgery, glycolysis was elevated in FVB, but not in Mb, hearts. Mb hearts were markedly more sensitive to TAC induced damage. Echocardiography revealed lower fractional shortening in Mb-TAC mice as well as larger left ventricular end diastolic and end systolic diameters. Cardiac hypertrophy and pulmonary congestion were more severe in Mb-TAC mice as indicated by the ratios of heart and lung weight to tibia length. Expression of α-MHC RNA was reduced more in Mb-TAC hearts than in FVB-TAC hearts. TAC produced a much greater increase in fibrosis of Mb hearts and this was accompanied by 5-fold more collagen 1 RNA expression in Mb-TAC versus FVB-TAC hearts. Mb-TAC hearts had the lowest phosphocreatine to ATP ratio and the most oxidative stress as indicated by higher cardiac content of 4-hydroxynonenal protein adducts. These results indicate that the heart's capacity to increase F-2,6-P(2 during pressure overload elevates glycolysis which is beneficial for reducing pressure overload induced cardiac hypertrophy, dysfunction and fibrosis.

  20. Overload and neovascularization of shoulder tendons in volleyball players

    Science.gov (United States)

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  1. Competing for Attention in Social Media under Information Overload Conditions

    CERN Document Server

    Feng, Ling; Li, Baowen; Stanley, H Eugene; Havlin, Shlomo; Braunstein, Lidia A

    2014-01-01

    Although the many forms of modern social media have become major channels for the dissemination of information, they are becoming overloaded because of the rapidly-expanding number of information feeds. We analyze the expanding user-generated content in Sina Weibo, the largest micro-blog site in China, and find evidence that popular messages often follow a mechanism that differs from that found in the spread of disease, in contrast to common believe. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that in contrast to epidemics, for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her. Thus the greater the number of friends an individual has the greater the number of repeated contacts needed to spread the message, which is a result of competition for attention. We model this process using a fractional susceptible infected recove...

  2. Game-Theoretic Models of Information Overload in Social Networks

    Science.gov (United States)

    Borgs, Christian; Chayes, Jennifer; Karrer, Brian; Meeder, Brendan; Ravi, R.; Reagans, Ray; Sayedi, Amin

    We study the effect of information overload on user engagement in an asymmetric social network like Twitter. We introduce simple game-theoretic models that capture rate competition between celebrities producing updates in such networks where users non-strategically choose a subset of celebrities to follow based on the utility derived from high quality updates as well as disutility derived from having to wade through too many updates. Our two variants model the two behaviors of users dropping some potential connections (followership model) or leaving the network altogether (engagement model). We show that under a simple formulation of celebrity rate competition, there is no pure strategy Nash equilibrium under the first model. We then identify special cases in both models when pure rate equilibria exist for the celebrities: For the followership model, we show existence of a pure rate equilibrium when there is a global ranking of the celebrities in terms of the quality of their updates to users. This result also generalizes to the case when there is a partial order consistent with all the linear orders of the celebrities based on their qualities to the users. Furthermore, these equilibria can be computed in polynomial time. For the engagement model, pure rate equilibria exist when all users are interested in the same number of celebrities, or when they are interested in at most two. Finally, we also give a finite though inefficient procedure to determine if pure equilibria exist in the general case of the followership model.

  3. Overload and neovascularization of shoulder tendons in volleyball players.

    Science.gov (United States)

    Notarnicola, Angela; Fischetti, Francesco; Gallone, Donato; Moretti, Lorenzo; Pignataro, Pasquale; Tafuri, Silvio; Moretti, Biagio

    2012-08-01

    In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional