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Sample records for cardiac myosin-binding protein

  1. Doxorubicin-induced carbonylation and degradation of cardiac myosin binding protein C promote cardiotoxicity

    OpenAIRE

    Aryal, Baikuntha; Jeong, Jinsook; Rao, V. Ashutosh

    2014-01-01

    Doxorubicin is one of the most successful anticancer agents. However, 10–30% of all treated patients experience a dose-limiting cardiac adverse event. Oxidative stress is partly responsible for the cardiotoxicity because the heart does not possess required antioxidant mechanisms. Protein oxidation by carbonylation is irreversible and marks proteins for loss of function and degradation. Using proteomics and MS, we identified and investigated cardiac myosin binding protein (MyBPC) as being sele...

  2. Novel control of cardiac myofilament response to calcium by S-glutahionylation at specific sites of myosin binding protein C

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    R.JohnSolaro

    2013-11-01

    Full Text Available Our previous studies demonstrated a relation between glutathionylation of cardiac myosin binding protein C and diastolic dysfunction in a hypertensive mouse model stressed by treatment with salt, deoxycorticosterone acetate, and unilateral nephrectomy. Although these results strongly indicated an important role for S-glutathionylation of myosin binding protein C as a modifier of myofilament function, indirect effects of other post-translational modifications may have occurred. Moreover, we did not determine the sites of thiol modification by glutathionylation. To address these issues, we developed an in vitro method to mimic the in situ S-glutathionylation of myofilament proteins and determined direct functional effects and sites of oxidative modification employing Western blotting and mass spectrometry. We induced glutathionylation in vitro by treatment of isolated myofibrils and detergent extracted fiber bundles (skinned fibers with oxidized glutathione (GSSG. Immuno-blotting results revealed increased glutathionylation with GSSG treatment of a protein band around 140 kDa. Using tandem mass spectrometry, we identified the 140 kDa band as cardiac myosin binding protein C and determined the sites of glutathionylation to be at cysteines 655, 479, and 627. Determination of the relation between Ca2+-activation of myofibrillar acto-myosin ATPase rate demonstrated an increased Ca2+-sensitivity induced by the S-glutathionylation. Force generating skinned fiber bundles also showed an increase in Ca-sensitivity when treated with oxidized glutathione, which was reversed with the reducing agent, dithiothreitol. Our data demonstrate that a specific and direct effect of S-glutathionylation of myosin binding protein C is a significant increase in myofilament Ca2+-sensitivity. Our data also provide new insights into the functional significance of oxidative modification of myosin binding protein C and the potential role of domains not previously considered to

  3. Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene.

    OpenAIRE

    Yu, B.; French, J. A.; Carrier, L.; Jeremy, R W; McTaggart, D R; Nicholson, M R; Hambly, B; Semsarian, C; Richmond, D R; Schwartz, K.; Trent, R.J.

    1998-01-01

    DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the mol...

  4. Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism

    OpenAIRE

    Mun, Ji Young; Previs, Michael J.; Yu, Hope Y.; Gulick, James; Tobacman, Larry S.; Beck Previs, Samantha; Robbins, Jeffrey; Warshaw, David M.; Craig, Roger

    2014-01-01

    Myosin-binding protein C (MyBP-C) is a component of myosin filaments, one of the two sets of contractile elements whose relative sliding is the basis of muscle contraction. In the heart, MyBP-C modulates contractility in response to cardiac stimulation; mutations in MyBP-C lead to cardiac disease. The mechanism by which MyBP-C modulates cardiac contraction is not understood. Using electron microscopy and a light microscopic assay for filament sliding, we demonstrate that MyBP-C binds to the o...

  5. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure.

    Science.gov (United States)

    Stathopoulou, Konstantina; Wittig, Ilka; Heidler, Juliana; Piasecki, Angelika; Richter, Florian; Diering, Simon; van der Velden, Jolanda; Buck, Friedrich; Donzelli, Sonia; Schröder, Ewald; Wijnker, Paul J M; Voigt, Niels; Dobrev, Dobromir; Sadayappan, Sakthivel; Eschenhagen, Thomas; Carrier, Lucie; Eaton, Philip; Cuello, Friederike

    2016-05-01

    Cardiac myosin-binding protein C (cMyBP-C) regulates actin-myosin interaction and thereby cardiac myocyte contraction and relaxation. This physiologic function is regulated by cMyBP-C phosphorylation. In our study, reduced site-specific cMyBP-C phosphorylation coincided with increased S-glutathiolation in ventricular tissue from patients with dilated or ischemic cardiomyopathy compared to nonfailing donors. We used redox proteomics, to identify constitutive and disease-specific S-glutathiolation sites in cMyBP-C in donor and patient samples, respectively. Among those, a cysteine cluster in the vicinity of the regulatory phosphorylation sites within the myosin S2 interaction domain C1-M-C2 was identified and showed enhanced S-glutathiolation in patients. In vitro S-glutathiolation of recombinant cMyBP-C C1-M-C2 occurred predominantly at Cys(249), which attenuated phosphorylation by protein kinases. Exposure to glutathione disulfide induced cMyBP-C S-glutathiolation, which functionally decelerated the kinetics of Ca(2+)-activated force development in ventricular myocytes from wild-type, but not those from Mybpc3-targeted knockout mice. These oxidation events abrogate protein kinase-mediated phosphorylation of cMyBP-C and therefore potentially contribute to the reduction of its phosphorylation and the contractile dysfunction observed in human heart failure.-Stathopoulou, K., Wittig, I., Heidler, J., Piasecki, A., Richter, F., Diering, S., van der Velden, J., Buck, F., Donzelli, S., Schröder, E., Wijnker, P. J. M., Voigt, N., Dobrev, D., Sadayappan, S., Eschenhagen, T., Carrier, L., Eaton, P., Cuello, F. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. PMID:26839380

  6. Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics.

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    Colson, Brett A; Thompson, Andrew R; Espinoza-Fonseca, L Michel; Thomas, David D

    2016-03-22

    We have used the site-directed spectroscopies of time-resolved fluorescence resonance energy transfer (TR-FRET) and double electron-electron resonance (DEER), combined with complementary molecular dynamics (MD) simulations, to resolve the structure and dynamics of cardiac myosin-binding protein C (cMyBP-C), focusing on the N-terminal region. The results have implications for the role of this protein in myocardial contraction, with particular relevance to β-adrenergic signaling, heart failure, and hypertrophic cardiomyopathy. N-terminal cMyBP-C domains C0-C2 (C0C2) contain binding regions for potential interactions with both thick and thin filaments. Phosphorylation by PKA in the MyBP-C motif regulates these binding interactions. Our spectroscopic assays detect distances between pairs of site-directed probes on cMyBP-C. We engineered intramolecular pairs of labeling sites within cMyBP-C to measure, with high resolution, the distance and disorder in the protein's flexible regions using TR-FRET and DEER. Phosphorylation reduced the level of molecular disorder and the distribution of C0C2 intramolecular distances became more compact, with probes flanking either the motif between C1 and C2 or the Pro/Ala-rich linker (PAL) between C0 and C1. Further insight was obtained from microsecond MD simulations, which revealed a large structural change in the disordered motif region in which phosphorylation unmasks the surface of a series of residues on a stable α-helix within the motif with high potential as a protein-protein interaction site. These experimental and computational findings elucidate structural transitions in the flexible and dynamic portions of cMyBP-C, providing previously unidentified molecular insight into the modulatory role of this protein in cardiac muscle contractility. PMID:26908877

  7. Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C

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    Riedemann Johann

    2011-05-01

    Full Text Available Abstract Background Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA. Efficient phosphorylation requires that PKA be anchored close to its targets by A-kinase anchoring proteins (AKAPs. Cardiac Myosin Binding Protein-C (cMyBPC and cardiac troponin I (cTNI are hypertrophic cardiomyopathy (HCM-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation. Results During a yeast 2-hybrid (Y2H library screen using a trisphosphorylation mimic of the C1-C2 region of cMyBPC, we identified isoform 4 of myomegalin (MMGL as an interactor of this N-terminal cMyBPC region. As MMGL has previously been shown to interact with phosphodiesterase 4D, we speculated that it may be a PKA-anchoring protein (AKAP. To investigate this possibility, we assessed the ability of MMGL isoform 4 to interact with PKA regulatory subunits R1A and R2A using Y2H-based direct protein-protein interaction assays. Additionally, to further elucidate the function of MMGL, we used it as bait to screen a cardiac cDNA library. Other PKA targets, viz. CARP, COMMD4, ENO1, ENO3 and cTNI were identified as putative interactors, with cTNI being the most frequent interactor. We further assessed and confirmed these interactions by fluorescent 3D-co-localization in differentiated H9C2 cells as well as by in vivo co-immunoprecipitation. We also showed that quantitatively more interaction occurs between MMGL and cTNI under β-adrenergic stress. Moreover, siRNA-mediated knockdown of MMGL leads to reduction of cMyBPC levels under conditions of adrenergic stress, indicating that MMGL-assisted phosphorylation is requisite for protection of cMyBPC against proteolytic cleavage. Conclusions This study ascribes a novel function to MMGL isoform 4: it meets all criteria for classification as an AKAP, and we show that is involved in the phosphorylation of cMyBPC as well as cTNI, hence MMGL

  8. Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart failure.

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    Cho-Kai Wu

    Full Text Available OBJECTIVE: Myosin binding protein C (MYBPC3 plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3 gene polymorphisms and diastolic heart failure (DHF in a human case-control study. METHODS: A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≥ 5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD structure of the MYBPC3 gene. RESULTS: In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031. The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25-3.66; p = 0.004 for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17-3.63; p = 0.013, corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C was also significantly associated with DHF (odds ratio 2.10 (1.53-2.89; permuted p = 0.029. CONCLUSIONS: We identified a SNP (rs2290149 among the tagging SNP set that was significantly associated with early DHF in a Chinese population.

  9. The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.

    Science.gov (United States)

    van Dijk, Sabine J; Bezold Kooiker, Kristina; Mazzalupo, Stacy; Yang, Yuanzhang; Kostyukova, Alla S; Mustacich, Debbie J; Hoye, Elaine R; Stern, Joshua A; Kittleson, Mark D; Harris, Samantha P

    2016-07-01

    Mutations in MYBPC3, the gene encoding cardiac myosin binding protein C (cMyBP-C), are a major cause of hypertrophic cardiomyopathy (HCM). While most mutations encode premature stop codons, missense mutations causing single amino acid substitutions are also common. Here we investigated effects of a single proline for alanine substitution at amino acid 31 (A31P) in the C0 domain of cMyBP-C, which was identified as a natural cause of HCM in cats. Results using recombinant proteins showed that the mutation disrupted C0 structure, altered sensitivity to trypsin digestion, and reduced recognition by an antibody that preferentially recognizes N-terminal domains of cMyBP-C. Western blots detecting A31P cMyBP-C in myocardium of cats heterozygous for the mutation showed a reduced amount of A31P mutant protein relative to wild-type cMyBP-C, but the total amount of cMyBP-C was not different in myocardium from cats with or without the A31P mutation indicating altered rates of synthesis/degradation of A31P cMyBP-C. Also, the mutant A31P cMyBP-C was properly localized in cardiac sarcomeres. These results indicate that reduced protein expression (haploinsufficiency) cannot account for effects of the A31P cMyBP-C mutation and instead suggest that the A31P mutation causes HCM through a poison polypeptide mechanism that disrupts cMyBP-C or myocyte function. PMID:26777460

  10. Double heterozygosity for mutations in the β-myosin heavy chain and in the cardiac myosin binding protein C genes in a family with hypertrophic cardiomyopathy

    OpenAIRE

    Richard, P.; Isnard, R.; Carrier, L.; Dubourg, O.; Donatien, Y.; Mathieu, B.; Bonne, G.; Gary, F; Charron, P; HAGEGE, A.; Komajda, M; Schwartz, K.; Hainque, B

    1999-01-01

    Familial hypertrophic cardiomyopathy is a genetically heterogeneous autosomal dominant disease, caused by mutations in several sarcomeric protein genes. So far, seven genes have been shown to be associated with the disease with the β-myosin heavy chain (MYH7) and the cardiac myosin binding protein C (MYBPC3) genes being the most frequently involved.
We performed electrocardiography (ECG) and echocardiography in 15 subjects with hypertrophic cardiomyopathy from a French Caribbean family. Genet...

  11. Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner.

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    Li Wang

    Full Text Available Based on our recent finding that cardiac myosin binding protein C (cMyBP-C phosphorylation affects muscle contractility in a site-specific manner, we further studied the force per cross-bridge and the kinetic constants of the elementary steps in the six-state cross-bridge model in cMyBP-C mutated transgenic mice for better understanding of the influence of cMyBP-C phosphorylation on contractile functions. Papillary muscle fibres were dissected from cMyBP-C mutated mice of ADA (Ala273-Asp282-Ala302, DAD (Asp273-Ala282-Asp302, SAS (Ser273-Ala282-Ser302, and t/t (cMyBP-C null genotypes, and the results were compared to transgenic mice expressing wide-type (WT cMyBP-C. Sinusoidal analyses were performed with serial concentrations of ATP, phosphate (Pi, and ADP. Both t/t and DAD mutants significantly reduced active tension, force per cross-bridge, apparent rate constant (2πc, and the rate constant of cross-bridge detachment. In contrast to the weakened ATP binding and enhanced Pi and ADP release steps in t/t mice, DAD mice showed a decreased ADP release without affecting the ATP binding and the Pi release. ADA showed decreased ADP release, and slightly increased ATP binding and cross-bridge detachment steps, whereas SAS diminished the ATP binding step and accelerated the ADP release step. t/t has the broadest effects with changes in most elementary steps of the cross-bridge cycle, DAD mimics t/t to a large extent, and ADA and SAS predominantly affect the nucleotide binding steps. We conclude that the reduced tension production in DAD and t/t is the result of reduced force per cross-bridge, instead of the less number of strongly attached cross-bridges. We further conclude that cMyBP-C is an allosteric activator of myosin to increase cross-bridge force, and its phosphorylation status modulates the force, which is regulated by variety of protein kinases.

  12. Genotype-phenotype correlation between the cardiac myosin binding protein C mutation A31P and hypertrophic cardiomyopathy in a cohort of Maine Coon cats

    DEFF Research Database (Denmark)

    Granström, S; Godiksen, M T N; Christiansen, M;

    2015-01-01

    OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color...... tissue Doppler imaging and occurrence of cardiac death during longitudinal follow-up in a cohort of Maine Coon cats. ANIMALS: The original cohort comprised 282 cats (158 of wild-type genotype, 99 heterozygous for A31P and 25 homozygous for A31P). METHODS: Prospective longitudinal study including...... echocardiography and registration of survival. RESULTS: The median age at the initial examination was 1.7 years (range, 0.8-9.2 years) and 6.4% (18/282) of the cats were diagnosed with HCM. One hundred sixty-five cats were eligible for echocardiographic re-examination, and during an average follow-up period of 2...

  13. Computational characterization of the mutation impact on domain C5 of Myosin Binding Protein C

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    Guardiani, Carlo; Cecconi, Fabio; Livi, Roberto

    2007-06-01

    Three mutations of domain C5 of Myosin Binding Protein C are involved in Familial Hypertrophic Cardiomyopathy. We assess their impact through Molecular Dynamics simulations within the framework of a native-centric coarse-grained model. We characterize the clinical relevance of a mutation by: the extent of temperature shift it induces in the unfolding transition, the increase of the kinetic unfolding rates with respect to the wild type, and by \\Fgr-value analysis. Further analysis of folding stages based on the evolution of native contact probabilities reveals an entropy-driven pathway originating in the protein region close to Res115 and ending up in the area of Res28. The mutation of the former residue thus appears to be responsible for an early interruption of the folding process, leaving the protein largely unstructured and yielding a serious impairment of cardiac function. Mut28, on the contrary, thwarts a late stage of folding when the protein is almost completely native-like, leading to a mild phenotype. A bio-informatic analisys of the long and destabilizing CD loop finally shows an excess of negative charge and a low hydrophobicity indicating a possible classification as a natively unfolded sequence. Accordingly, the folding mechanism is suggested to be coupled with binding with a specific ligand.

  14. Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

    KAUST Repository

    Conti, Antonio

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS\\'s pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V.

  15. Myosin Binding Protein-C Slow: a multifaceted family of proteins with a complex expression profile in fast and slow twitch skeletal muscles

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    Maegen A Ackermann

    2013-12-01

    Full Text Available Myosin Binding Protein-C slow (sMyBP-C comprises a complex family of proteins expressed in slow and fast type skeletal muscles. Similar to its fast and cardiac counterparts, sMyBP-C functions to modulate the formation of actomyosin cross-bridges, and to organize and stabilize sarcomeric A- and M-bands. The slow form of MyBP-C was originally classified as a single protein, however several variants encoded by the single MYBPC1 gene have been recently identified. Alternative splicing of the 5’ and 3’ ends of the MYBPC1 transcript has led to the differential expression of small unique segments interspersed between common domains. In addition, the NH2-terminus of sMyBP-C undergoes complex phosphorylation. Thus, alternative splicing and phosphorylation appear to regulate the functional activities of sMyBP-C. sMyBP-C proteins are not restricted to slow twitch muscles, but they are abundantly expressed in fast twitch muscles, too. Using bioinformatic tools, we herein perform a systematic comparison of the known human and mouse sMyBP-C variants. In addition, using single fiber westerns and antibodies to a common region of all known sMyBP-C variants, we present a detailed and comprehensive characterization of the expression profile of sMyBP-C proteins in the slow twitch soleus and the fast twitch flexor digitorum brevis (FDB mouse muscles. Our studies demonstrate for the first time that distinct sMyBP-C variants are co-expressed in the same fiber, and that their expression profile differs among fibers. Given the differential expression of sMyBP-C variants in single fibers, it becomes apparent that each variant or combination thereof may play unique roles in the regulation of actomyosin cross-bridges formation and the stabilization of thick filaments.

  16. Mortality risk of untreated myosin-binding protein C-related hypertrophic cardiomyopathy: insight into the natural history

    NARCIS (Netherlands)

    E.A. Nannenberg; M. Michels; I. Christiaans; D. Majoor-Krakauer; Y.M. Hoedemaekers; J.P. van Tintelen; M.P. Lombardi; F.J. ten Cate; A.F.L. Schinkel; J.G.P. Tijssen; I.M. van Langen; A.A.M. Wilde; E.J.G. Sijbrands

    2011-01-01

    The goal of this study was to assess the mortality of hypertrophic cardiomyopathy (HCM), partly in times when the disease was not elucidated and patients were untreated. HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is needed to design prope

  17. Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or α-Tropomyosin Mutation for Hypertrophic Cardiomyopathy

    OpenAIRE

    Marisa Ojala; Chandra Prajapati; Risto-Pekka Pölönen; Kristiina Rajala; Mari Pekkanen-Mattila; Jyrki Rasku; Kim Larsson; Katriina Aalto-Setälä

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in ...

  18. Statistical Thermodynamics for Actin-Myosin Binding: The Crucial Importance of Hydration Effects.

    Science.gov (United States)

    Oshima, Hiraku; Hayashi, Tomohiko; Kinoshita, Masahiro

    2016-06-01

    Actomyosin is an important molecular motor, and the binding of actin and myosin is an essential research target in biophysics. Nevertheless, the physical factors driving or opposing the binding are still unclear. Here, we investigate the role of water in actin-myosin binding using the most reliable statistical-mechanical method currently available for assessing biomolecules immersed in water. This method is characterized as follows: water is treated not as a dielectric continuum but as an ensemble of molecules; the polyatomic structures of proteins are taken into consideration; and the binding free energy is decomposed into physically insightful entropic and energetic components by accounting for the hydration effect to its full extent. We find that the actin-myosin binding brings large gains of electrostatic and Lennard-Jones attractive interactions. However, these gains are accompanied by even larger losses of actin-water and myosin-water electrostatic and LJ attractive interactions. Although roughly half of the energy increase due to the losses is cancelled out by the energy decrease arising from structural reorganization of the water released upon binding, the remaining energy increase is still larger than the energy decrease brought by the gains mentioned above. Hence, the net change in system energy is positive, which opposes binding. Importantly, the binding is driven by a large gain of configurational entropy of water, which surpasses the positive change in system energy and the conformational entropy loss occurring for actin and myosin. The principal physical origin of the large water-entropy gain is as follows: the actin-myosin interface is closely packed with the achievement of high shape complementarity on the atomic level, leading to a large increase in the total volume available to the translational displacement of water molecules in the system and a resultant reduction of water crowding (i.e., entropic correlations among water molecules). PMID

  19. Mitochondrial Protein Dynamics in Cardiac Remodeling

    OpenAIRE

    Lau, Edward

    2014-01-01

    The cardiac mitochondrial proteome contains ~1,500 distinct proteins that carry out necessary metabolic and energetic processes in the heart. To sustain cardiac function, the mitochondrial proteome must be maintained in constant renewal, or turnover, especially under stress conditions. Disruptions of protein turnover can lead to protein damage and proteotoxicity, a hallmark of many heart disease etiologies. Current quantitative proteomics experiments largely focus on the measurement of the st...

  20. ADP-stimulated contraction: A predictor of thin-filament activation in cardiac disease.

    Science.gov (United States)

    Sequeira, Vasco; Najafi, Aref; Wijnker, Paul J M; Dos Remedios, Cristobal G; Michels, Michelle; Kuster, Diederik W D; van der Velden, Jolanda

    2015-12-15

    Diastolic dysfunction is general to all idiopathic dilated (IDCM) and hypertrophic cardiomyopathy (HCM) patients. Relaxation deficits may result from increased actin-myosin formation during diastole due to altered tropomyosin position, which blocks myosin binding to actin in the absence of Ca(2+). We investigated whether ADP-stimulated force development (without Ca(2+)) can be used to reveal changes in actin-myosin blockade in human cardiomyopathy cardiomyocytes. Cardiac samples from HCM patients, harboring thick-filament (MYH7mut, MYBPC3mut) and thin-filament (TNNT2mut, TNNI3mut) mutations, and IDCM were compared with sarcomere mutation-negative HCM (HCMsmn) and nonfailing donors. Myofilament ADP sensitivity was higher in IDCM and HCM compared with donors, whereas it was lower for MYBPC3. Increased ADP sensitivity in IDCM, HCMsmn, and MYH7mut was caused by low phosphorylation of myofilament proteins, as it was normalized to donors by protein kinase A (PKA) treatment. Troponin exchange experiments in a TNNT2mut sample corrected the abnormal actin-myosin blockade. In MYBPC3trunc samples, ADP sensitivity highly correlated with cardiac myosin-binding protein-C (cMyBP-C) protein level. Incubation of cardiomyocytes with cMyBP-C antibody against the actin-binding N-terminal region reduced ADP sensitivity, indicative of cMyBP-C's role in actin-myosin regulation. In the presence of Ca(2+), ADP increased myofilament force development and sarcomere stiffness. Enhanced sarcomere stiffness in sarcomere mutation-positive HCM samples was irrespective of the phosphorylation background. In conclusion, ADP-stimulated contraction can be used as a tool to study how protein phosphorylation and mutant proteins alter accessibility of myosin binding on actin. In the presence of Ca(2+), pathologic [ADP] and low PKA-phosphorylation, high actin-myosin formation could contribute to the impaired myocardial relaxation observed in cardiomyopathies. PMID:26621701

  1. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

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    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

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

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    Jung, Joanna; Dyck, Jason R. B.; Lopaschuk, Gary D.; Agellon, Luis B.; Michalak, Marek

    2016-01-01

    Background Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR) pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function. Methodology/Principal Findings We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER) homeostasis, transient activation of the unfolded protein response (UPR) pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA) is sufficient to prevent cardiac fibrosis, and improved exercise tolerance. Conclusions We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function. PMID:27441395

  3. Mitogen-activated protein kinase (MAPK) in cardiac tissues.

    Science.gov (United States)

    Page, C; Doubell, A F

    Mitogen-activated protein kinase (MAPK) has recently emerged as a prominent role player in intracellular signalling in the ventricular myocyte with attention being focussed on its possible role in the development of ventricular hypertrophy. It is becoming clear that MAPK is also active in other cells of cardiac origin such as cardiac fibroblasts and possible functions of this signalling pathway in the heart have yet to be explored. In this report the mammalian MAPK pathway is briefly outlined, before reviewing current knowledge of the MAPK pathway in cardiac tissue (ventricular myocytes, vascular smooth muscle cells and cardiac fibroblasts). New data is also presented on the presence and activity of MAPK in two additional cardiac celltypes namely atrial myocytes and vascular endothelial cells from the coronary microcirculation. PMID:8739228

  4. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I;

    2009-01-01

    secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...

  5. Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins.

    Science.gov (United States)

    Gross, Sean M; Lehman, Steven L

    2016-06-01

    Protein phosphorylation plays an important role in regulating cardiac contractile function, but phosphorylation is not thought to play a regulatory role in skeletal muscle. To examine how myofilament phosphorylation arose in the human heart, we analyzed the amino acid sequences of 25 cardiac phosphorylation sites in animals ranging from fruit flies to humans. These analyses indicated that of the 25 human phosphorylation sites examined, 11 have been conserved across vertebrates and four have been sporadically present in vertebrates. Furthermore, all 11 of the cardiac sites found across vertebrates were present in skeletal muscle isoforms, along with three sites that were sporadically present. Based on the conservation of amino acid sequences between cardiac and skeletal contractile proteins, we tested for phosphorylation in mammalian skeletal muscle using several biochemical techniques and found evidence that multiple myofilament proteins were phosphorylated. Several of these phosphorylation sites were validated using mass spectrometry, including one site that is present in slow- and fast-twitch troponin I (TnI), but was lost in cardiac TnI. Thus, several myofilament phosphorylation sites present in the human heart likely arose in invertebrate muscle, have been evolutionarily conserved in skeletal muscle, and potentially have functional effects in both skeletal and cardiac muscle. PMID:26993364

  6. Dephosphorylation of chicken cardiac myofibril C-protein by protein phosphatases 1 and 2A

    International Nuclear Information System (INIS)

    C-Protein, which is a regulatory component of cardiac muscle myofibrils, is phosphorylated in response to β-adrenergic agonists by a cAMP-dependent mechanism and dephosphorylated in response to cholinergic agonists. It is believed that the cAMP-dependent phosphorylation is due to cAMP-dependent protein kinase. The protein phosphatase(s) involved in the dephosphorylation of C-protein has not been determined. In this study, chicken cardiac C-protein was phosphorylated with the cAMP-dependent protein kinase to about 3 mol phosphate/mol C-protein. Incubation of [32P]C-protein with the catalytic subunit of protein phosphatase 1 or 2A rapidly removed 30-40% of 32[P]. Phosphopeptide maps and phosphoamino acid analysis revealed that the major site(s) dephosphorylated by either phosphatase was a phosphothreonine residue(s) located on the same tryptic peptide and on the same CNBr fragment. Increasing the incubation period or the phosphatase concentration did not result in any further dephosphorylation of C-protein by phosphatase 1, but phosphatase 2A completely dephosphorylated C-protein. Preliminary studies showed that the major protein phosphatase associated with the myofibril was phosphatase 2A. These results indicate the phosphatase 2A may be important in the regulation of the phosphorylation state of C-protein

  7. Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yutaka; Matsui; Junko; Morimoto; Toshimitsu; Uede

    2010-01-01

    After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.

  8. Molecule specific effects of PKA-mediated phosphorylation on rat isolated heart and cardiac myofibrillar function.

    Science.gov (United States)

    Hanft, Laurin M; Cornell, Timothy D; McDonald, Colin A; Rovetto, Michael J; Emter, Craig A; McDonald, Kerry S

    2016-07-01

    Increased cardiac myocyte contractility by the β-adrenergic system is an important mechanism to elevate cardiac output to meet hemodynamic demands and this process is depressed in failing hearts. While increased contractility involves augmented myoplasmic calcium transients, the myofilaments also adapt to boost the transduction of the calcium signal. Accordingly, ventricular contractility was found to be tightly correlated with PKA-mediated phosphorylation of two myofibrillar proteins, cardiac myosin binding protein-C (cMyBP-C) and cardiac troponin I (cTnI), implicating these two proteins as important transducers of hemodynamics to the cardiac sarcomere. Consistent with this, we have previously found that phosphorylation of myofilament proteins by PKA (a downstream signaling molecule of the beta-adrenergic system) increased force, slowed force development rates, sped loaded shortening, and increased power output in rat skinned cardiac myocyte preparations. Here, we sought to define molecule-specific mechanisms by which PKA-mediated phosphorylation regulates these contractile properties. Regarding cTnI, the incorporation of thin filaments with unphosphorylated cTnI decreased isometric force production and these changes were reversed by PKA-mediated phosphorylation in skinned cardiac myocytes. Further, incorporation of unphosphorylated cTnI sped rates of force development, which suggests less cooperative thin filament activation and reduced recruitment of non-cycling cross-bridges into the pool of cycling cross-bridges, a process that would tend to depress both myocyte force and power. Regarding MyBP-C, PKA treatment of slow-twitch skeletal muscle fibers caused phosphorylation of MyBP-C (but not slow skeletal TnI (ssTnI)) and yielded faster loaded shortening velocity and ∼30% increase in power output. These results add novel insight into the molecular specificity by which the β-adrenergic system regulates myofibrillar contractility and how attenuation of PKA

  9. H2O2 alters rat cardiac sarcomere function and protein phosphorylation through redox signaling

    OpenAIRE

    Avner, Benjamin S.; Hinken, Aaron C.; Yuan, Chao; Solaro, R. John

    2010-01-01

    ROS, such as H2O2, are a component of pathological conditions in many organ systems and have been reported to be elevated in cardiac pathophysiology. The experiments presented here test the hypothesis that H2O2 induces alterations in cardiac myofilament function by the posttranslational modification of sarcomeric proteins indirectly through PKC signaling. In vitro assessment of actomyosin Mg2+-ATPase activity of myofibrillar fractions showed blunted relative ATP consumption in the relaxed sta...

  10. Role for the Unfolded Protein Response in Heart Disease and Cardiac Arrhythmias

    OpenAIRE

    Man Liu; Dudley, Samuel C

    2015-01-01

    The unfolded protein response (UPR) has been extensively investigated in neurological diseases and diabetes, while its function in heart disease is less well understood. Activated UPR participates in multiple cardiac conditions and can either protect or impair heart function. Recently, the UPR has been found to play a role in arrhythmogenesis during human heart failure by affecting cardiac ion channels expression, and blocking UPR has an antiarrhythmic effect. This review will discuss the rat...

  11. Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

    OpenAIRE

    Liang, Yan; Sheikh, Farah

    2016-01-01

    The mitogen activated protein kinase (MAPK)-extracellular regulated kinase 1/2 (ERK1/2) pathway is a central downstream signaling pathway that is activated in cardiac muscle cells during mechanical and agonist-mediated hypertrophy. Studies in genetic mouse models deficient in ERK-associated MAPK components pathway have further reinforced a direct role for this pathway in stress-induced cardiac hypertrophy and disease. However, more recent studies have highlighted that these signaling pathways...

  12. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins

    OpenAIRE

    Soni, Siddarth; Raaijmakers, Antonia J. A.; Raaijmakers, Linsey M.; Damen, J. Mirjam A.; van Stuijvenberg, Leonie; Vos, Marc A.; Heck, Albert J.R.; van Veen, Toon A. B.; Scholten, Arjen

    2016-01-01

    Aims Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID). The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore ...

  13. Exendin-4 Improves Cardiac Function in Mice Overexpressing Monocyte Chemoattractant Protein-1 in Cardiomyocytes

    OpenAIRE

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A.; Smith, Layton H.; Kolattukudy, Pappachan; Julio E Ayala

    2014-01-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit ...

  14. Quantitative phosphoproteomics using acetone-based peptide labeling: method evaluation and application to a cardiac ischemia/reperfusion model.

    Science.gov (United States)

    Wijeratne, Aruna B; Manning, Janet R; Schultz, Jo El J; Greis, Kenneth D

    2013-10-01

    Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. An MS-based strategy utilizing an inexpensive acetone-based peptide-labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Because the chemistry for RABA labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 versus hearts expressing low-molecular-weight fibroblast growth factor-2 (LMW FGF2) to relate low-molecular-weight fibroblast growth factor-2 (LMW FGF2)-mediated cardioprotective phenomena induced by ischemia/reperfusion injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins, including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g., connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g., cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification phosphoproteomic

  15. Novel Phenotype–Genotype Correlations of Restrictive Cardiomyopathy With Myosin-Binding Protein C (MYBPC3) Gene Mutations Tested by Next-Generation Sequencing

    OpenAIRE

    Wu, Wei; Lu, Chao-Xia; Wang, Yi-Ning; Liu, Fang; Chen, Wei; Liu, Yong-Tai; Han, Ye-Chen; Cao, Jian; Zhang, Shu-Yang; Zhang, Xue

    2015-01-01

    Background MYBPC3 dysfunctions have been proven to induce dilated cardiomyopathy, hypertrophic cardiomyopathy, and/or left ventricular noncompaction; however, the genotype–phenotype correlation between MYBPC3 and restrictive cardiomyopathy (RCM) has not been established. The newly developed next-generation sequencing method is capable of broad genomic DNA sequencing with high throughput and can help explore novel correlations between genetic variants and cardiomyopathies. Methods and Results ...

  16. Serum high-sensitivity C-reaction protein and heart fatty acid binding protein level and cardiac accidents in patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    朱红秋

    2006-01-01

    Objective To investigate the relationship between serum high-sensitivity C-reaction protein (hs-CRP) and heart fatty acid binding protein (h-FABP) on cardiac accidents in patients with unstable angina pectoris (UAP). Methods Serum levels of hs-CRP, h-FABP, cardiac troponin-Ⅰ(cTn-Ⅰ) and creatine kinase MB isoenzyme (CK-MB) were measured and cardiac accidents within 2 weeks after the test were observed in 74 patients (male

  17. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing.

    NARCIS (Netherlands)

    Maatz, H.; Jens, M.; Liss, M.; Schafer, S.; Heinig, M.; Kirchner, M.; Adami, E.; Rintisch, C.; Dauksaite, V.; Radke, M.H.; Selbach, M.; Barton, P.J.; Cook, S.A.; Rajewsky, N.; Gotthardt, M.; Landthaler, M.; Hubner, N.

    2014-01-01

    Mutations in the gene encoding the RNA-binding protein RBM20 have been implicated in dilated cardiomyopathy (DCM), a major cause of chronic heart failure, presumably through altering cardiac RNA splicing. Here, we combined transcriptome-wide crosslinking immunoprecipitation (CLIP-seq), RNA-seq, and

  18. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    Science.gov (United States)

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  19. Transitions of protein traffic from cardiac ER to junctional SR

    OpenAIRE

    Sleiman, Naama H.; McFarland, Timothy P.; Jones, Larry R.; Cala, Steven E.

    2015-01-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca2+ release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appe...

  20. Impact of anesthesia and storage on posttranslational modifications of cardiac myofilament proteins

    OpenAIRE

    Utter, Megan S.; Warren, Chad M.; Solaro, R. John

    2015-01-01

    Although high fidelity measurements of posttranslational modifications (PTMs) of cardiac myofilament proteins exist, important issues remain regarding basic techniques of sample acquisition and storage. We investigated the effects of anesthetic regimen and sample storage conditions on PTMs of major ventricular sarcomeric proteins. Mice were anesthetized with pentobarbital (Nembutal), ketamine/xylazine mixture (Ket/Xyl), or tribromoethanol (Avertin), and the ventricular tissue was prepared and...

  1. Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review.

    Science.gov (United States)

    Imbalzano, Egidio; Mandraffino, Giuseppe; Casciaro, Marco; Quartuccio, Sebastiano; Saitta, Antonino; Gangemi, Sebastiano

    2016-09-01

    S100 proteins are a family of highly acidic calcium-binding proteins involved in calcium handling in many tissues and organs. Some of these proteins are highly expressed in cardiac tissue, and an impairment of some specific S100 proteins has been related to heart failure. To check this hypothesis, we decided to review the literature since 2008 until May 2015. According to the studies collected, recovering S100A1 levels may enhance contractile/relaxing performance in heart failure, reverse negative force-frequency relationship, improve contractile reserve, reverse diastolic dysfunction and protect against pro-arrhythmic reductions of sarcoplasmic reticulum calcium. The safety profile of gene therapy was also confirmed. Increased S100B protein levels were related to a worse outcome in chronic heart failure. S100A8/A9 complex plasma levels, as well as other inflammatory biomarkers, were significantly higher in chronic heart failure patients. S100A2 seems to increase both contractile and relaxation performance in animal cardiomyocytes. Otherwise, S100A6 cardiac expression seems to have no effects on contractility. S100A4 KO mice showed reduced cardiac interstitial fibrosis. Data collected encourage a potential prospective application in human. These proteins could be exploited as biomarkers in stadiation and prognosis of chronic heart failure, as well as therapeutic target to rescue failing heart. Registration details The study protocol has been registered in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ) under registration number CRD42015027932. PMID:26833319

  2. C-Reactive Protein Inhibits Survivin Expression via Akt/mTOR Pathway Downregulation by PTEN Expression in Cardiac Myocytes

    OpenAIRE

    Beom Seob Lee; Soo Hyuk Kim; Jaewon Oh; Taewon Jin; Eun Young Choi; Sungha Park; Sang-Hak Lee; Ji Hyung Chung; Seok-Min Kang

    2014-01-01

    C-reactive protein (CRP) is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We ...

  3. Pivotal Role of Regulator of G-protein Signaling 12 in Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    Huang, Jia; Chen, Lijuan; Yao, Yuyu; Tang, Chengchun; Ding, Jiandong; Fu, Cong; Li, Hongliang; Ma, Genshan

    2016-06-01

    Cardiac hypertrophy is a major predictor of heart failure and is regulated by diverse signaling pathways. As a typical multi-domain member of the regulator of G-protein signaling (RGS) family, RGS12 plays a regulatory role in various signaling pathways. However, the precise effect of RGS12 on cardiac hypertrophy remains largely unknown. In this study, we observed increased expression of RGS12 in the development of pathological cardiac hypertrophy and heart failure. We then generated genetically engineered mice and neonatal rat cardiomyocytes to investigate the effects of RGS12 during this pathological process. Four weeks after aortic banding, RGS12-deficient hearts showed decreased cardiomyocyte cross area (374.7±43.2 μm(2) versus 487.1±47.9 μm(2) in controls; Prequirement of the MEK1/2-ERK1/2 signaling for RGS12-mediated cardiac hypertrophy was confirmed in rescue experiments using the MEK1/2-specific inhibitor U0126. In conclusion, our findings provide a novel diagnostic and therapeutic target for pathological cardiac hypertrophy and heart failure. PMID:27091895

  4. Transitions of protein traffic from cardiac ER to junctional SR.

    Science.gov (United States)

    Sleiman, Naama H; McFarland, Timothy P; Jones, Larry R; Cala, Steven E

    2015-04-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca(2+) release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQ-DsRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed ((del)TRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and (del)TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic. PMID:25640161

  5. Heterotopic cardiac transplantation decreases the capacity for rat myocardial protein synthesis

    International Nuclear Information System (INIS)

    Heterotopic cardiac isografts are vascularly perfused hearts that maintain structural and functional integrity for prolonged periods of time. When placed in an infrarenal location, the heart is hemodynamically unloaded and undergoes negative growth, leading to cardiac atrophy. At 7 and 14 days after transplantation, the transplanted heart was decreased in size compared with the in situ heart (p less than 0.001). To assess the possible mechanism(s) to account for this reduction in size we studied in vivo rates of total left ventricular (LV) protein synthesis, total LV RNA content, and 18S ribosomal RNA content by nucleic acid hybridization. The LV protein synthetic rate was 4.7 and 5.3 mg/day in the in situ heart and was significantly decreased to 2.9 and 2.7 mg/day in the transplanted hearts at 7 and 14 days, respectively. LV RNA content of the transplant declined to 53% and 48% of the in situ value at 7 and 14 days, respectively. Hybridization studies revealed that LV 18S ribosomal subunit content was reduced proportionately to total RNA in the heterotopic hearts. As a result of these changes, there was no significant difference in the efficiency of total LV protein synthesis between the in situ and transplanted hearts. The present studies demonstrate that the hemodynamic unloading and cardiac atrophy that is characteristic of heterotopic cardiac transplantation is accompanied by a decrease in LV total RNA content and 18S RNA, resulting in a decreased capacity for myocardial protein synthesis

  6. Serial study of C reactive protein concentrations in cardiac allograft recipients.

    OpenAIRE

    Harkiss, G.D.

    1985-01-01

    C reactive protein (CRP) concentrations were measured serially in 38 patients after cardiac transplantation. Three of 28 patients (11%) had raised values before transplantation. After transplantation, most patients showed rises in CRP concentrations associated with transplant surgery which became normal by day 7. Thereafter, 75/274 samples (28%) from 18/38 patients (47%) had raised CRP values. Most of the rises in CRP concentration were associated with infection (78%), which in most cases was...

  7. Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives

    OpenAIRE

    Javadov, Sabzali; Jang, Sehwan; Agostini, Bryan

    2014-01-01

    Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and cross-talk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myria...

  8. Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives

    Science.gov (United States)

    Javadov, Sabzali; Jang, Sehwan; Agostini, Bryan

    2014-01-01

    Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and cross-talk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myriad of mitogens and stressors and influencing the signaling of cardiac development, metabolism, performance, and pathogenesis. Definitive relationships between MAPK signaling and cardiac dysfunction remain elusive, despite 30 years of extensive clinical studies and basic research of various animal/cell models, severities of stress, and types of stimuli. Still, several studies have proven the importance of MAPK cross-talk with mitochondria, powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte function and play a crucial role in cell death. Although many questions remain unanswered, there exists enough evidence to consider the possibility of targeting MAPK-mitochondria interactions in the prevention and treatment of heart disease. The goal of this review is to integrate previous studies into a discussion of MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial infarction (ischemia), hypertrophy and heart failure. A comprehensive understanding of relevant molecular mechanisms, as well as challenges for studies in this area, will facilitate the development of new pharmacological agents and genetic manipulations for therapy of cardiovascular diseases. PMID:24924700

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

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

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

  10. Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins

    Directory of Open Access Journals (Sweden)

    Safa Abdul-Ghani

    2014-01-01

    Full Text Available Remote ischemic preconditioning (RIPC induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200 mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5 min of limb ischemia followed by 5 min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC.

  11. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins

    Science.gov (United States)

    Soni, Siddarth; Raaijmakers, Antonia J. A.; Raaijmakers, Linsey M.; Damen, J. Mirjam A.; van Stuijvenberg, Leonie; Vos, Marc A.; Heck, Albert J. R.

    2016-01-01

    Aims Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID). The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue. Methods and Results General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF) and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2), Nexilin (NEXN), Popeye-domain-containg-protein 2 (POPDC2) and thioredoxin-related-transmembrane-protein 2 (TMX2)) and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes. Conclusion The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart. PMID:27148881

  12. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins.

    Directory of Open Access Journals (Sweden)

    Siddarth Soni

    Full Text Available Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID. The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue.General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2, Nexilin (NEXN, Popeye-domain-containg-protein 2 (POPDC2 and thioredoxin-related-transmembrane-protein 2 (TMX2 and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes.The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart.

  13. Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells

    International Nuclear Information System (INIS)

    Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium. (author)

  14. C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Beom Seob Lee

    Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

  15. Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats

    Directory of Open Access Journals (Sweden)

    Guidot David M

    2008-04-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 infection and the consequent acquired immunodeficiency syndrome (AIDS has protean manifestations, including muscle wasting and cardiomyopathy, which contribute to its high morbidity. The pathogenesis of these myopathies remains partially understood, and may include nutritional deficiencies, biochemical abnormalities, inflammation, and other mechanisms due to viral infection and replication. Growing evidence has suggested that HIV-1-related proteins expressed by the host in response to viral infection, including Tat and gp120, may also be involved in the pathophysiology of AIDS, particularly in cells or tissues that are not directly infected with HIV-1. To explore the potentially independent effects of HIV-1-related proteins on heart and skeletal muscles, we used a transgenic rat model that expresses several HIV-1-related proteins (e.g., Tat, gp120, and Nef. Outcome measures included basic heart and skeletal muscle morphology, glutathione metabolism and oxidative stress, and gene expressions of atrogin-1, muscle ring finger protein-1 (MuRF-1 and Transforming Growth Factor-β1 (TGFβ1, three factors associated with muscle catabolism. Results Consistent with HIV-1 associated myopathies in humans, HIV-1 transgenic rats had increased relative heart masses, decreased relative masses of soleus, plantaris and gastrocnemius muscles, and decreased total and myosin heavy chain type-specific plantaris muscle fiber areas. In both tissues, the levels of cystine (Cyss, the oxidized form of the anti-oxidant cysteine (Cys, and Cyss:Cys ratios were significantly elevated, and cardiac tissue from HIV-1 transgenic rats had altered glutathione metabolism, all reflective of significant oxidative stress. In HIV-1 transgenic rat hearts, MuRF-1 gene expression was increased. Further, HIV-1-related protein expression also increased atrogin-1 (~14- and ~3-fold and TGFβ1 (~5-fold and ~3-fold in heart and

  16. Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion

    OpenAIRE

    Shinpei Kadowaki; Tetsuro Shishido; Toshiki Sasaki; Takayuki Sugai; Taro Narumi; Yuki Honda; Yoichiro Otaki; Daisuke Kinoshita; Tetsuya Takahashi; Satoshi Nishiyama; Hiroki Takahashi; Takanori Arimoto; Takuya Miyamoto; Tetsu Watanabe; Akihiko Ishigami

    2016-01-01

    Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary ar...

  17. Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Gavillet, Bruno; van Bemmelen, Miguel X; Cordonier, Sophie; Thomas, Marc A; Staub, Olivier; Abriel, Hugues

    2006-01-01

    In order to identify proteins interacting with the cardiac voltage-gated sodium channel Na(v)1.5, we used the last 66 amino acids of the C-terminus of the channel as bait to screen a human cardiac cDNA library. We identified the protein tyrosine phosphatase PTPH1 as an interacting protein. Pull-d...

  18. Preoperative protein and energy intake and postoperative complications in well-nourished, non-hospitalized elderly cardiac surgery patients

    NARCIS (Netherlands)

    L.M.W. van Venrooij; P.A.M. van Leeuwen; R. de Vos; M.M.M.J. Borgmeijer-Hoelen; B.A.J.M. de Mol

    2009-01-01

    Background & aims: Little is known about the impact of preoperative protein or energy intake in relation to the occurrence of postoperative complications in patients who are not undernourished but cannot keep up their daily protein or energy requirements prior to cardiac surgery. Therefore, a prospe

  19. Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish

    Directory of Open Access Journals (Sweden)

    Joshua D. Wythe

    2011-09-01

    The vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1, which we show is required for normal function and morphogenesis of the embryonic zebrafish heart. Hadp1 is a pleckstrin homology (PH-domain-containing protein whose expression is enriched in embryonic cardiomyocytes. Knockdown of hadp1 in zebrafish embryos reduced cardiac contractility and altered late myocyte differentiation. By using optical mapping and submaximal levels of hadp1 knockdown, we observed profound effects on Ca2+ handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca2+ handling in the heart. Hadp1 interacts with phosphatidylinositol 4-phosphate [PI4P; also known as PtdIns(4P] derivatives via its PH domain, and its subcellular localization is dependent upon this motif. Pharmacological blockade of the synthesis of PI4P derivatives in vivo phenocopied the loss of hadp1 in zebrafish. Collectively, these results demonstrate that hadp1 is required for normal cardiac function and morphogenesis during embryogenesis, and suggest that hadp1 modulates Ca2+ handling in the heart through its interaction with phosphatidylinositols.

  20. Promyelocytic leukemia zinc finger protein activates GATA4 transcription and mediates cardiac hypertrophic signaling from angiotensin II receptor 2.

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    Ning Wang

    Full Text Available BACKGROUND: Pressure overload and prolonged angiotensin II (Ang II infusion elicit cardiac hypertrophy in Ang II receptor 1 (AT(1 null mouse, whereas Ang II receptor 2 (AT(2 gene deletion abolishes the hypertrophic response. The roles and signals of the cardiac AT(2 receptor still remain unsettled. Promyelocytic leukemia zinc finger protein (PLZF was shown to bind to the AT(2 receptor and transmit the hypertrophic signal. Using PLZF knockout mice we directed our studies on the function of PLZF concerning the cardiac specific transcription factor GATA4, and GATA4 targets. METHODOLOGY AND PRINCIPAL FINDINGS: PLZF knockout and age-matched wild-type (WT mice were treated with Ang II, infused at a rate of 4.2 ng·kg(-1·min(-1 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in PLZF knockout and WT mice (140 mmHg. WT mice developed prominent cardiac hypertrophy and fibrosis after Ang II infusion. In contrast, there was no obvious cardiac hypertrophy or fibrosis in PLZF knockout mice. An AT(2 receptor blocker given to Ang II-infused wild type mice prevented hypertrophy, verifying the role of AT(2 receptor for cardiac hypertrophy. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that PLZF bound to the GATA4 gene regulatory region. A Luciferase assay verified that PLZF up-regulated GATA4 gene expression and the absence of PLZF expression in vivo produced a corresponding repression of GATA4 protein. CONCLUSIONS: PLZF is an important AT(2 receptor binding protein in mediating Ang II induced cardiac hypertrophy through an AT(2 receptor-dependent signal pathway. The angiotensin II-AT(2-PLZF-GATA4 signal may further augment Ang II induced pathological effects on cardiomyocytes.

  1. C- Reactive protein, cardiac troponin T and low albumin are predictors of mortality in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Bagheri Nazila

    2009-01-01

    Full Text Available Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP. The aim of study was to determine whether CRP, low albumin and troponin are markers of overall and cardiovascular mortality in hemodialysis patients. 138 stable hemodialysis patients were divided into 2 groups n= 66 patients with coronary disease equivalent (known coronary or peripheral vascular disease or diabetes mellitus and n= 72 patients without it. The two groups were then stratified by biomarkers [cardiac troponin T and Albumin and highly sensitive CRP (hs-CRP] and followed for 30 months. The primary outcome was all causes mortality. Patients with coronary disease equivalents had 3.5 fold greater annual mortality compared to controls (24%% vs 6.9%, P value = 0.005. Elevated troponin T had a further increase in the risk for death while hs-CRP and low albumin were not associated with risk of death In conclusion, circu-lating cardiac troponin-T was associated with poor prognosis especially in hemodialysis patients with coronary risk factors.

  2. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing.

    Science.gov (United States)

    Maatz, Henrike; Jens, Marvin; Liss, Martin; Schafer, Sebastian; Heinig, Matthias; Kirchner, Marieluise; Adami, Eleonora; Rintisch, Carola; Dauksaite, Vita; Radke, Michael H; Selbach, Matthias; Barton, Paul J R; Cook, Stuart A; Rajewsky, Nikolaus; Gotthardt, Michael; Landthaler, Markus; Hubner, Norbert

    2014-08-01

    Mutations in the gene encoding the RNA-binding protein RBM20 have been implicated in dilated cardiomyopathy (DCM), a major cause of chronic heart failure, presumably through altering cardiac RNA splicing. Here, we combined transcriptome-wide crosslinking immunoprecipitation (CLIP-seq), RNA-seq, and quantitative proteomics in cell culture and rat and human hearts to examine how RBM20 regulates alternative splicing in the heart. Our analyses revealed the presence of a distinct RBM20 RNA-recognition element that is predominantly found within intronic binding sites and linked to repression of exon splicing with RBM20 binding near 3' and 5' splice sites. Proteomic analysis determined that RBM20 interacts with both U1 and U2 small nuclear ribonucleic particles (snRNPs) and suggested that RBM20-dependent splicing repression occurs through spliceosome stalling at complex A. Direct RBM20 targets included several genes previously shown to be involved in DCM as well as genes not typically associated with this disease. In failing human hearts, reduced expression of RBM20 affected alternative splicing of several direct targets, indicating that differences in RBM20 expression may affect cardiac function. Together, these findings identify RBM20-regulated targets and provide insight into the pathogenesis of human heart failure. PMID:24960161

  3. Cardiac hypertrophy and failure--a disease of adaptation. Modifications in membrane proteins provide a molecular basis for arrhythmogenicity.

    Science.gov (United States)

    Moalic, J M; Charlemagne, D; Mansier, P; Chevalier, B; Swynghedauw, B

    1993-05-01

    Cardiac hypertrophy is the physiological adaptation of the heart to chronic mechanical overload. Cardiac failure indicates the limits of the process. Cardiac hypertrophy is only one example of biological adaptation and results from the induction of several changes in gene expression, mostly of the fetal type, including those coding for the myosin heavy chain or the alpha-subunit of the Na+,K(+)-ATPase. From a thermodynamic point of view, the decrease in Vmax allows the heart to produce a normal tension at a lower cost. This process results from changes both in the sarcomere and in the expression of certain membrane proteins. The decrease in calcium transient is determined by several changes in membrane proteins that result in a rather fragile equilibrium in terms of calcium homeostasis. Any abnormal input in calcium will have exaggerated detrimental consequences on a hypertrophied myocyte and may cause automaticity and arrhythmias or an exaggerated response to anoxia in terms of compliance. PMID:8485830

  4. Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction.

    Directory of Open Access Journals (Sweden)

    Makiko Miyata

    Full Text Available BACKGROUND: Senescence marker protein 30 (SMP30, which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX-induced cardiac dysfunction. METHODS AND RESULTS: SMP30 knockout (SMP30 KO mice, SMP30 transgenic (SMP30 TG mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT littermate mice at 12-14 weeks of age were given intra-peritoneal injection of DOX (20 mg/kg or saline. Five days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of reactive oxygen species and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The numbers of deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive nuclei in the myocardium, apoptotic signaling pathways such as caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation activity of c-Jun N-terminal kinase were increased in SMP30 KO mice and decreased in SMP30 TG mice compared with WT mice after DOX injection. CONCLUSIONS: SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure.

  5. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYP ERTROPHY

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

    Objective To investigate the change of c-myc protein, which was chosen as the response indicator to volume-overload. Methods The time and spatial course of c-myc protein expressi on on the model of rat cardiac volume-overload hyper trophy was examined by immunohistochemical study. Results The immunohistochemica l study indicated the expression of c-myc protein was increased obviously at 4 -6 hours (62.73%) than that of control (45.41%, P<0.01) after the volume-o verload, then decreased gradually along with development of volume-overload hyp ertrophy and was decreased extremely at 5 months(r=-0.514,P<0.01).Conclusion There are disorders in the signal transduction pathways governing the hypertrophic respon se of cardiomyocytes in hypertrophic myocardium. C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy. Once switching on, c-myc gene and the product of it do not act anymore;While it may be that c-my c gene and the product of it increased following with myocardial hypertrophy, an d have not direct relation to the occurrence and development of myocardial hyper trophy.

  6. VARIATION AND SIGNIFICANCE OF C-MYC PROTEIN IN RAT CARDIAC VOLUME-OVERLOAD HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the change of c-myc protein,which was chosen as the response indicator to volume-overloab.Methods:The time and spatial course of c-myc protein expression on the model of rat cardiac volume-overload hypertrophy was examined by immunohistochemical study.Results:The immunohistochemical study indicated the expression of c-myc protein was increased obviously at 4-6 hours(62.73%)than that of control(45.41%,P<0.01) after the volume-overload,then decreased gradually along with development of volume-overload hypertrophy and was decreased extremely at 5 months(r=-0.514,p<0.01),Conclusion:There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in hypertrophic myocardium.C-myc gene and the product of it may be only the promoter gene of myocardial hypertrophy.Once switching on,c-myc gene and the product of it do not act anymore;While it may be that c-myc gene and the product of it increased following with myocardial hypertrophy,and have not direct relation to the occurrence and development of myocardial hypertrophy.

  7. Dephosphorylation specificities of protein phosphatase for cardiac troponin I, troponin T, and sites within troponin T

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Protein dephosphorylation by protein phosphatase 1 (PP1, acting in concert with protein kinase C (PKC and protein kinase A (PKA, is a pivotal regulatory mechanism of protein phosphorylation. Isolated rat cardiac myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 were used in determining dephosphorylation specificities, Ca2+-stimulated Mg2+ATPase activities, and Ca2+ sensitivities. In reconstituted troponin (Tn complex, PP1 displayed distinct substrate specificity in dephosphorylation of TnT preferentially to TnI, in vitro. In situ phosphorylation of cardiomyocytes with calyculin A, a protein phosphatase inhibitor, resulted in an increase in the phosphorylation stiochiometry of TnT (0.3 to 0.5 (67%, TnI (2.6 to 3.6 (38%, and MLC2 (0.4 to 1.7 (325%. These results further confirmed that though MLC2 is the preferred target substrate for protein phosphatase in the thick filament, the Tn complex (TnI and TnT from thin filament and C-protein in the thick filament are also protein phosphatase substrates. Our in vitro dephosphorylation experiments revealed that while PP1 differentially dephosphorylated within TnT at multiple sites, TnI was uniformly dephosphorylated. Phosphopeptide maps from the in vitro experiments show that TnT phosphopeptides at spots 4A and 4B are much more resistant to PP1 dephosphorylation than other TnT phosphopeptides. Mg2+ATPase assays of myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 delineated that while PKC and PKA phosphorylation decreased the Ca2+-stimulated Mg2+ATPase activities, dephosphorylation antagonistically restored it. PKC and PKA phosphorylation decreased Ca2+ sensitivity to 3.6 µM and 5.0 µM respectively. However, dephosphorylation restored the Mg2+ATPase activity of PKC (99% and PKA (95%, along with the Ca2+ sensitivities (3.3 µM and 3.0 µM, respectively.

  8. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  9. Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies

    Science.gov (United States)

    Tomasov, Pavol; Villard, Eric; Faludi, Reka; Melacini, Paola; Lossie, Janine; Lohmann, Nadine; Richard, Pascale; De Bortoli, Marzia; Angelini, Annalisa; Varga-Szemes, Akos; Sperling, Silke R.; Simor, Tamás; Veselka, Josef; Özcelik, Cemil; Charron, Philippe

    2016-01-01

    Introduction Transgenic mice overexpressing mutated NEBL, encoding the cardiac-specific Z-disk protein nebulette, develop severe cardiac phenotypes. Since cardiomyopathies are commonly familial and because mutations in a single gene may result in variable phenotypes, we tested the hypothesis that NEBL mutations are associated with cardiomyopathy. Material and methods We analyzed 389 patients, including cohorts of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular non-compaction cardiomyopathy (LVNC). The 28 coding exons of the NEBL gene were sequenced. Further bioinformatic analysis was used to distinguish variants. Results In total, we identified six very rare heterozygous missense mutations in NEBL in 7 different patients (frequency 1.8%) in highly conserved codons. The mutations were not detectable in 320 Caucasian sex-matched unrelated individuals without cardiomyopathy and 192 Caucasian sex-matched blood donors without heart disease. Known cardiomyopathy genes were excluded in these patients. The mutations p.H171R and p.I652L were found in 2 HCM patients. Further, p.Q581R and p.S747L were detected in 2 DCM patients, while the mutation p.A175T was identified independently in two unrelated patients with DCM. One LVNC patient carried the mutation p.P916L. All HCM and DCM related mutations were located in the nebulin-like repeats, domains responsible for actin binding. Interestingly, the mutation associated with LVNC was located in the C-terminal serine-rich linker region. Conclusions Our data suggest that NEBL mutations may cause various cardiomyopathies. We herein describe the first NEBL mutations in HCM and LVNC. Our findings underline the notion that the cardiomyopathies are true allelic diseases.

  10. Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes

    International Nuclear Information System (INIS)

    Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2+-channel current (ICa) through the opposite actions for two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of ICa by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on ICa was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function

  11. Protein kinase G signaling in cardiac pathophysiology: Impact of proteomics on clinical trials.

    Science.gov (United States)

    Kirk, Jonathan A; Holewinski, Ronald J; Crowgey, Erin L; Van Eyk, Jennifer E

    2016-03-01

    The protective role of cyclic guanosine monophosphate (cGMP)-stimulated protein kinase G (PKG) in the heart makes it an attractive target for therapeutic drug development to treat a variety of cardiac diseases. Phosphodiesterases degrade cGMP, thus phosphodiesterase inhibitors that can increase PKG are of translational interest and the subject of ongoing human trials. PKG signaling is complex, however, and understanding its downstream phosphorylation targets and upstream regulation are necessary steps toward safe and efficacious drug development. Proteomic technologies have paved the way for assays that allow us to peer broadly into signaling minutia, including protein quantity changes and phosphorylation events. However, there are persistent challenges to the proteomic study of PKG, such as the impact of the expression of different PKG isoforms, changes in its localization within the cell, and alterations caused by oxidative stress. PKG signaling is also dependent upon sex and potentially the genetic and epigenetic background of the individual. Thus, the rigorous application of proteomics to the field will be necessary to address how these effectors can alter PKG signaling and interfere with pharmacological interventions. This review will summarize PKG signaling, how it is being targeted clinically, and the proteomic challenges and techniques that are being used to study it. PMID:26670943

  12. Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes.

    OpenAIRE

    Parker, T G; Packer, S E; Schneider, M. D.

    1990-01-01

    Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide growth factors, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes. Transforming growth factor-beta 1 (TGF beta 1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes ...

  13. Type III Transforming Growth Factor-β Receptor Drives Cardiac Hypertrophy Through β-Arrestin2-Dependent Activation of Calmodulin-Dependent Protein Kinase II.

    Science.gov (United States)

    Lou, Jie; Zhao, Dan; Zhang, Ling-Ling; Song, Shu-Ying; Li, Yan-Chao; Sun, Fei; Ding, Xiao-Qing; Yu, Chang-Jiang; Li, Yuan-Yuan; Liu, Mei-Tong; Dong, Chang-Jiang; Ji, Yong; Li, Hongliang; Chu, Wenfeng; Zhang, Zhi-Ren

    2016-09-01

    The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac

  14. Protein kinase C betaII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Omiyi, Didi; Brue, Richard J; Taormina, Philip; Harvey, Margaret; Atkinson, Norrell; Young, Lindon H

    2005-08-01

    Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs. PMID:15878997

  15. Evaluation of C-reactive protein, Haptoglobin and cardiac Troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome.

    OpenAIRE

    Planellas Marta; Cuenca Rafaela; Tabar Maria-Dolores; Bertolani Coralie; Poncet Cyrill; Closa Josep M; Lorente Juan; Cerón Jose J; Pastor Josep

    2012-01-01

    Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructiv...

  16. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  17. Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs contributing to regeneration of the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1αMSCs.Controls included native MSCs ((NatMSCs and MSCs transduced with an empty vector ((NullMSCs. PKG1α activity was increased approximately 20, 5 and 16 fold respectively in (PKG1αMSCs. (PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in (PKG1αMSCs compared to (NatMSCs and (NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, (PKG1αMSCs group showed higher survival compared with (NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of (PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and (NullMSCs group, (PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05 and attenuated infarct size (27.2±2.5%, p<0.01. Heart function indices including ejection fraction (52.1±2.2%, p<0.01 and fractional shortening (24.8%±1.3%, p<0.01 were improved significantly in (PKG1αMSCs group. CONCLUSION: Overexpression of PKG1α transgene could be a powerful approach to improve MSCs

  18. Purification of phospholamban, a 22,000 dalton protein from cardiac sarcoplasmic reticulum that is specifically phosphorylated by cyclic AMP-dependent protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Bidlack, J.M.; Shamoo, A.E.

    1979-01-01

    Very low concentrations deoxycholate (DOC) were used to isolate two proteins from canine cardiac sarcoplasmic reticulum. These two proteins are phospholamban, a 22,000 dalton protein, and the Ca/sup 2 +/ + Mg/sup 2 +/-ATPase, the major protein of the sarcoplasmic reticulum, responsible for the active transport of calcium. The 22,000 dalton protein is first solubilized in a very low concentration of DOC and then subjected to column chromatography. After molecular weight sieving on a Sephadex G-75 column, the 22,000 dalton protein appears as a purified protein on sodium dodecyl sulfate (SDS)-polyacrylamide gels. The purified protein is specifically phosphorylated by cyclic AMP-dependent protein kinase. Phospholipids are still bound to the isolated protein. The Ca/sup 2 +/ + Mg/sup 2 +/-ATPase is purified by first solubilizing all the extrinsic proteins with a low concentration of DOC. An increasing amount of DOC is then added to yield the purified Ca/sup 2 +/ + Mg/sup 2 +/-ATPase. This protein is at least 95% pure. Adding additional DOC to the purified enzyme enhances the enzyme's ability to hydrolyze ATP. (ERB)

  19. Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells.

    Science.gov (United States)

    Moscoso, Isabel; Tejados, Naiara; Barreiro, Olga; Sepúlveda, Pilar; Izarra, Alberto; Calvo, Enrique; Dorronsoro, Akaitz; Salcedo, Juan Manuel; Sádaba, Rafael; Díez-Juan, Antonio; Trigueros, César; Bernad, Antonio

    2016-07-01

    Cardiac progenitor cells (CPCs) from adult myocardium offer an alternative cell therapy approach for ischaemic heart disease. Improved clinical performance of CPCs in clinical trials requires a comprehensive definition of their biology and specific interactions with the environment. In this work we characterize specific human CPC surface markers and study some of their related functions. c-kit(pos) human CPCs (hCPCs) were characterized for cell surface marker expression, pluripotency, early and late cardiac differentiation markers and therapeutic activity in a rat model of acute myocardial infarction. The results indicate that hCPCs are a mesenchymal stem cell (MSC)-like population, with a similar immunoregulatory capacity. A partial hCPC membrane proteome was analysed by liquid chromatography-mass spectrometry/mass spectrometry and 36 proteins were identified. Several, including CD26, myoferlin and podocalyxin-like protein 1 (PODXL), have been previously described in other stem-cell systems. Suppression and overexpression analysis demonstrated that PODXL regulates hCPC activation, migration and differentiation; it also modulates their local immunoregulatory capacity. Therefore, hCPCs are a resident cardiac population that shares many features with hMSCs, including their capacity for local immunoregulation. Expression of PODXL appears to favour the immature state of hCPCs, while its downregulation facilitates their differentiation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:23897803

  20. Proteomic analysis of age dependent nitration of rat cardiac proteins by solution isoelectric focusing coupled to nano-HPLC tandem mass spectrometry

    OpenAIRE

    Hong, Sung Jung; Gokulrangan, Giridharan; Schöneich, Christian

    2007-01-01

    Protein nitration occurs as a result of oxidative stress induced by reactive oxygen (ROS) and reactive nitrogen species (RNS). Therefore, protein nitration serves as a hallmark for protein oxidation in vivo. We have previously reported on age dependent protein nitration in cardiac tissue of Fisher 344 BN-F1 rats analyzed by two-dimensional gel electrophoresis; however, only one specific nitration site was identified (Kanski et al., 2005a). In the present report, we used solution phase isoelec...

  1. Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events

    OpenAIRE

    Klauß, Volker; Siebert, Uwe; Wasem, Jürgen; Grabein, Kristin; Stollenwerk, Björn; Grandi, Norma; Schnell-Inderst, Petra; Schwarzer, Ruth; Göhler, Alexander

    2009-01-01

    Background: In a substantial portion of patients (= 25%) with coronary heart disease (CHD), a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP) in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-...

  2. Rapid Diagnosis of acute kidney injury (AKI) associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP) biomarker

    OpenAIRE

    Mirbagheri L; Master of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran; Farhadi N; Taghipour H R; Mirbagheri M; Nourani M R

    2012-01-01

    Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI). Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP) as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour) andafter cardiac surgery for detectio...

  3. Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qing Fu; Xiao-Ying Li; Xiao-Chun Lu; Ya-Fei Mi; Tao Liu; Wei-Hua Ye

    2012-01-01

    Background Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin Ⅱ) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory

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

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

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

  5. The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers

    Science.gov (United States)

    Touhara, Kouki K; Wang, Weiwei; MacKinnon, Roderick

    2016-01-01

    G protein gated inward rectifier potassium (GIRK) channels are gated by direct binding of G protein beta-gamma subunits (Gβγ), signaling lipids, and intracellular Na+. In cardiac pacemaker cells, hetero-tetramer GIRK1/4 channels and homo-tetramer GIRK4 channels play a central role in parasympathetic slowing of heart rate. It is known that the Na+ binding site of the GIRK1 subunit is defective, but the functional difference between GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers remains unclear. Here, using purified proteins and the lipid bilayer system, we characterize Gβγ and Na+ regulation of GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers. We find in GIRK4 homo-tetramers that Na+ binding increases Gβγ affinity and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to Gβγ, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound. DOI: http://dx.doi.org/10.7554/eLife.15750.001 PMID:27074664

  6. Role of the scaffolding protein Homer 1a in cardiac hypertrophy

    OpenAIRE

    Chiarello, Carmelina

    2013-01-01

    Homer proteins are a family of scaffolding proteins involved in many intracellular signaling pathways, in both excitable and non-excitable cells. These proteins participate in the assembly and regulation of functional signaling complexes, facilitating the cross-talk between surface membrane receptors and channels in the membranes of intracellular compartments (Worley PF. et al., 2007). Homer proteins are constitutively expressed in the brain, where their scaffolding function is important for ...

  7. Green tea polyphenols improve cardiac muscle mRNA, and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats

    Science.gov (United States)

    Epidemiologic studies indicate that the consumption of green tea polyphenols (GTP) may reduce the risk of coronary artery disease. To explore the underlying mechanisms of action at the molecular level, we examined the effects of GTP on cardiac mRNA and protein levels of genes involved in insulin an...

  8. Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats.

    Directory of Open Access Journals (Sweden)

    Xiao Lan Lu

    Full Text Available Gαq protein carboxyl terminus imitation polypeptide (GCIP-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin.Forty-eight rats were randomly divided into the following six groups receiving vehicle (control, doxorubicin (Dox, losartan (6 mg/kg, i.g. and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid, respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC, Bcl-2, protein kinase C (PKC ε and phosphorylated extracellular signal-regulated kinase (p-ERK 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27.

  9. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Directory of Open Access Journals (Sweden)

    Tamara P. Martin

    2014-01-01

    Full Text Available Phosphorylated heat shock protein 20 (HSP20 is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

  10. Designing proteins to combat disease: Cardiac troponin C as an example.

    Science.gov (United States)

    Davis, Jonathan P; Shettigar, Vikram; Tikunova, Svetlana B; Little, Sean C; Liu, Bin; Siddiqui, Jalal K; Janssen, Paul M L; Ziolo, Mark T; Walton, Shane D

    2016-07-01

    Throughout history, muscle research has led to numerous scientific breakthroughs that have brought insight to a more general understanding of all biological processes. Potentially one of the most influential discoveries was the role of the second messenger calcium and its myriad of handling and sensing systems that mechanistically control muscle contraction. In this review we will briefly discuss the significance of calcium as a universal second messenger along with some of the most common calcium binding motifs in proteins, focusing on the EF-hand. We will also describe some of our approaches to rationally design calcium binding proteins to palliate, or potentially even cure cardiovascular disease. Considering not all failing hearts have the same etiology, genetic background and co-morbidities, personalized therapies will need to be developed. We predict designer proteins will open doors for unprecedented personalized, and potentially, even generalized medicines as gene therapy or protein delivery techniques come to fruition. PMID:26901433

  11. C-reactive protein as a predictor for cardiac events in Chinese elderly patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Guangyong HUANG; Caiyi LU; Xingli WU; Yuxiao ZHANG

    2006-01-01

    Background and objective To assess the predictive value of C-reactive protein(CRP) for major adverse cardiac events and the association between CRP level and the coronary lesion morphology and extent in patients with coronary heart disease (CHD).Methods CRP was measured on admission in 177 consecutive elderly (age≥60 years) patients with CHD who underwent coronary angiography. Patients were divided into high CRP group (CRP≥3mg/L) and normal CRP group (CRP <3mg/L). The association between CRP levels and the coronary lesion features, including severity of stenosis (mild, moderate, severe), extent of lesion (diffused or nondiffused), eccentricity of the plaque (eccentric or non-eccentric) were analyzed. Patients were followed up for a mean of 8 months for the occurrences of major adverse cardiac events (MACE). Results Compared with patients in normal CRP group, patients in high CRP group were more frequently to have unstable angina, multi-vessel, diffuse, eccentric lesions, positive remodeling, and non-smooth plaques (P<0.01). Kaplan-Meier analysis showed patients in high CRP group had a significantly lower MACE-free survival rate than patients in normal CRP group (Log-rank = 12.0, P<0.01); Cox regression analysis indicated CRP level as an independent predictor for the occurrence of MACE (OR=3.16, P<0.05) Conclusions High CRP level is associated with more extend, severe and eccentric coronary lesions and is an independent predictor for MACE in elderly patients with CHD.

  12. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

    Directory of Open Access Journals (Sweden)

    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  13. Baseline leukocyte count and acute coronary syndrome: predictor of adverse cardiac events, long and short term mortality and association with traditional risk factors, cardiac biomarkers and C-reactive protein

    International Nuclear Information System (INIS)

    The elevated WBC count has been accepted as part of healing response following myocardial infarction as well as a predictor of adverse cardiovascular events. The study was designed to find out correlation between WBC count and coronary risk factors, cardiac biomarkers, C-reactive protein (CRP), incidence of adverse cardiac events and mortality in patients of ACS in Pakistan. Methods: One hundred and thirty-three patients of ACS were stratified according to WBC categories, WBC1 (10,000/mm/sup 3/). The WBCs were counted on admission by Sysmex cell counter, CRP by immunoturbidimetric method, and CK-MB and Trop-I by enzyme immunoassay. Adverse cardiac events and mortality were recorded for 12 months of follow up period. Results: Long term mortality in patients with ACS was 6.4% in WBC1, 18.2% in WBC2 and 40.9% in WBC3 categories, while short term mortality was 2.6%, 3.0% and 18.2% in WBC1, WBC2, and WBC3 categories respectively. Relative to patients in lower 2 WBC categories, patients in the highest category were 7 times more likely to die during 30 days (HR 7.83, p=0.017) and more than 9 times during the total follow up period (HR 9.42, p<0.001). Cox regression analysis showed WBC3 a strong independent predictor of mortality (HR 6.36, p=0.016). WBC count showed a positive correlation with coronary risk factors, cardiac biomarkers and CRP. Conclusion: WBC count is a strong independent predictor of mortality in patients with ACS and has positive correlation with coronary risk factors, cardiac biomarkers and CRP. (author)

  14. Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1.

    Science.gov (United States)

    Jespersen, Thomas; Gavillet, Bruno; van Bemmelen, Miguel X; Cordonier, Sophie; Thomas, Marc A; Staub, Olivier; Abriel, Hugues

    2006-10-01

    In order to identify proteins interacting with the cardiac voltage-gated sodium channel Na(v)1.5, we used the last 66 amino acids of the C-terminus of the channel as bait to screen a human cardiac cDNA library. We identified the protein tyrosine phosphatase PTPH1 as an interacting protein. Pull-down experiments confirmed the interaction, and indicated that it depends on the PDZ-domain binding motif of Na(v)1.5. Co-expression experiments in HEK293 cells showed that PTPH1 shifts the Na(v)1.5 availability relationship toward hyperpolarized potentials, whereas an inactive PTPH1 or the tyrosine kinase Fyn does the opposite. The results of this study suggest that tyrosine phosphorylation destabilizes the inactivated state of Na(v)1.5. PMID:16930557

  15. Cardiac Risk Assessment

    Science.gov (United States)

    ... to assess cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring ... LDL-C but does not respond to typical strategies to lower LDL-C such as diet, exercise, ...

  16. Muscle LIM Protein: Master regulator of cardiac and skeletal muscle functions.

    Science.gov (United States)

    Vafiadaki, Elizabeth; Arvanitis, Demetrios A; Sanoudou, Despina

    2015-07-15

    Muscle LIM Protein (MLP) has emerged as a key regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, are causative of human cardiomyopathies, whereas altered expression patterns are observed in human failing heart and skeletal myopathies. In vitro and in vivo evidences reveal a complex and diverse functional role of MLP in striated muscle, which is determined by its multiple interacting partners and subcellular distribution. Experimental evidence suggests that MLP is implicated in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles still unfolds. PMID:25936993

  17. Potassium Channel Interacting Protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling.

    Science.gov (United States)

    Winther, Sine V; Tuomainen, Tomi; Borup, Rehannah; Tavi, Pasi; Antoons, Gudrun; Thomsen, Morten B

    2016-01-01

    The heart-failure relevant Potassium Channel Interacting Protein 2 (KChIP2) augments CaV1.2 and KV4.3. KChIP3 represses CaV1.2 transcription in cardiomyocytes via interaction with regulatory DNA elements. Hence, we tested nuclear presence of KChIP2 and if KChIP2 translocates into the nucleus in a Ca(2+) dependent manner. Cardiac biopsies from human heart-failure patients and healthy donor controls showed that nuclear KChIP2 abundance was significantly increased in heart failure; however, this was secondary to a large variation of total KChIP2 content. Administration of ouabain did not increase KChIP2 content in nuclear protein fractions in anesthetized mice. KChIP2 was expressed in cell lines, and Ca(2+) ionophores were applied in a concentration- and time-dependent manner. The cell lines had KChIP2-immunoreactive protein in the nucleus in the absence of treatments to modulate intracellular Ca(2+) concentration. Neither increasing nor decreasing intracellular Ca(2+) concentrations caused translocation of KChIP2. Microarray analysis did not identify relief of transcriptional repression in murine KChIP2(-/-) heart samples. We conclude that although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca(2+). Thus, KChIP2 does not function as a conventional transcription factor in the heart. PMID:27349185

  18. Characterization of Ca2+-Dependent Protein-Protein Interactions within the Ca2+ Release Units of Cardiac Sarcoplasmic Reticulum

    Science.gov (United States)

    Rani, Shilpa; Park, Chang Sik; Sreenivasaiah, Pradeep Kumar; Kim, Do Han

    2016-01-01

    In the heart, excitation-contraction (E-C) coupling is mediated by Ca2+ release from sarcoplasmic reticulum (SR) through the interactions of proteins forming the Ca2+ release unit (CRU). Among them, calsequestrin (CSQ) and histidine-rich Ca2+ binding protein (HRC) are known to bind the charged luminal region of triadin (TRN) and thus directly or indirectly regulate ryanodine receptor 2 (RyR2) activity. However, the mechanisms of CSQ and HRC mediated regulation of RyR2 activity through TRN have remained unclear. We first examined the minimal KEKE motif of TRN involved in the interactions with CSQ2, HRC and RyR2 using TRN deletion mutants and in vitro binding assays. The results showed that CSQ2, HRC and RyR2 share the same KEKE motif region on the distal part of TRN (aa 202–231). Second, in vitro binding assays were conducted to examine the Ca2+ dependence of protein-protein interactions (PPI). The results showed that TRN-HRC interaction had a bell-shaped Ca2+ dependence, which peaked at pCa4, whereas TRN-CSQ2 or TRN-RyR2 interaction did not show such Ca2+ dependence pattern. Third, competitive binding was conducted to examine whether CSQ2, HRC, or RyR2 affects the TRN-HRC or TRN-CSQ2 binding at pCa4. Among them, only CSQ2 or RyR2 competitively inhibited TRN-HRC binding, suggesting that HRC can confer functional refractoriness to CRU, which could be beneficial for reloading of Ca2+ into SR at intermediate Ca2+ concentrations. PMID:26674963

  19. C- Reactive protein, cardiac troponin T and low albumin are predictors of mortality in hemodialysis patients

    OpenAIRE

    Bagheri Nazila; Taziki Omolbanin; Falaknazi Kianoosh

    2009-01-01

    Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP). The aim of study was to determine whether CRP, low albumin and troponin are markers of overall and cardiovascular mortality in hemodialysis patients. 138 stable hemodialysis patients were divided into 2 groups n= 66 patients with coronary disease equivalent (known coronary or peripheral vascular disease or diabetes mellitus) and n= 72 patients without it. The two grou...

  20. Cardiac Period 2 in myocardial ischemia: Clinical implications of a light dependent protein

    OpenAIRE

    Bonney, Stephanie; Hughes, Kelly; Harter, Patrick N.; Mittelbronn, Michel; Walker, Lori; Eckle, Tobias

    2013-01-01

    Since the onset of myocardial infarction and stroke has distinct circadian patterns, the disruption of circadian rhythms may contribute to cardiovascular disease. A recent clinical study, reporting that the severity of myocardial ischemia depends on the time-of-day when ischemia occurs, highlights the impact of circadian rhythms on cardiovascular disease. In support of these observations, we found a cardioprotective role of the circadian rhythm protein Period 2 (Per2) during myocardial ischem...

  1. Heat shock protein 72 expression in the right ventricle of patients undergoing congenital cardiac surgery.

    Directory of Open Access Journals (Sweden)

    Nakamura K

    2000-06-01

    Full Text Available While heat shock protein (HSP 72 is known as a stress protein, there have been no reports of HSP 72 expression in patients who have undergone surgery for congenital heart disease. Fourteen patients (7 males and 7 females who had undergone surgery for congenital heart disease were studied. The ages of the patients ranged from 2 months to 43 years old (mean 6.5 +/- 10.8 years old; median 3.0 years old. The diagnoses were Tetralogy of Fallot in seven, pulmonary atresia with ventricular septal defect (VSD in three, complex anomalies in three, and VSD in one patient. Histological study and HSP analysis using Western blots and immunostaining with anti-HSP 72 monoclonal antibody were performed for right ventricular muscle samples resected during the surgery. The histological findings showed hypertrophic changes of ventricular cardiomyocytes in all samples studied. Western blots detected HSP 72 expression of various degrees in all specimens. Immunostaining using monoclonal antibody against HSP 72 showed that the protein was present in the nuclei and cytoplasm of cardiomyocytes. In conclusion, although it is difficult to determine the cause of the "stress" that triggers HSP 72 expression in cardiomyocytes, low O2 saturation and pressure overload might act as a "stress", and the only common factor that induced HSP 72 in every sample was hypertrophy.

  2. Signal transduction and activator of transcription (STAT) protein-dependent activation of angiotensinogen promoter: A cellular signal for hypertrophy in cardiac muscle

    OpenAIRE

    Mascareno, Eduardo; Dhar, Manya; M.A.Q. SIDDIQUI

    1998-01-01

    The role of the peptide hormone angiotensin (AngII) in promoting myocardial hypertrophy is well documented. Our studies demonstrate that AngII uses a signaling pathway in cardiac myocytes in which the promoter of the gene encoding its prohormone, angiotensinogen, serves as the target site for activated signal transduction and activator of transcription (STAT) proteins. Gel mobility-shift assay revealed that STAT3 and STAT6 are selectively activated by AngII treatment of cardiomyocytes in cult...

  3. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    OpenAIRE

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Mat...

  4. Protein Kinase G1 α Overexpression Increases Stem Cell Survival and Cardiac Function after Myocardial Infarction

    OpenAIRE

    Linlin Wang; Zeeshan Pasha; Shuyun Wang; Ning Li; Yuliang Feng; Gang Lu; Millard, Ronald W.; Muhammad Ashraf

    2013-01-01

    BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α) could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs) contributing to regeneration of the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1α)MSCs).Controls included native MSCs ((Nat)MSCs) and MSCs transduced with an empty vector ((Null)MSCs). PKG1α activity was increased appr...

  5. Infrared fluorescent protein 1.4 genetic labeling tracks engrafted cardiac progenitor cells in mouse ischemic hearts.

    Directory of Open Access Journals (Sweden)

    Lijuan Chen

    Full Text Available Stem cell therapy has a potential for regenerating damaged myocardium. However, a key obstacle to cell therapy's success is the loss of engrafted cells due to apoptosis or necrosis in the ischemic myocardium. While many strategies have been developed to improve engrafted cell survival, tools to evaluate cell efficacy within the body are limited. Traditional genetic labeling tools, such as GFP-like fluorescent proteins (eGFP, DsRed, mCherry, have limited penetration depths in vivo due to tissue scattering and absorption. To circumvent these limitations, a near-infrared fluorescent mutant of the DrBphP bacteriophytochrome from Deinococcus radiodurans, IFP1.4, was developed for in vivo imaging, but it has yet to be used for in vivo stem/progenitor cell tracking. In this study, we incorporated IFP1.4 into mouse cardiac progenitor cells (CPCs by a lentiviral vector. Live IFP1.4-labeled CPCs were imaged by their near-infrared fluorescence (NIRF using an Odyssey scanner following overnight incubation with biliverdin. A significant linear correlation was observed between the amount of cells and NIRF signal intensity in in vitro studies. Lentiviral mediated IFP1.4 gene labeling is stable, and does not impact the apoptosis and cardiac differentiation of CPC. To assess efficacy of our model for engrafted cells in vivo, IFP1.4-labeled CPCs were intramyocardially injected into infarcted hearts. NIRF signals were collected at 1-day, 7-days, and 14-days post-injection using the Kodak in vivo multispectral imaging system. Strong NIRF signals from engrafted cells were imaged 1 day after injection. At 1 week after injection, 70% of the NIRF signal was lost when compared to the intensity of the day 1 signal. The data collected 2 weeks following transplantation showed an 88% decrease when compared to day 1. Our studies have shown that IFP1.4 gene labeling can be used to track the viability of transplanted cells in vivo.

  6. Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

    Science.gov (United States)

    de Castro, Alexandre Luz; Fernandes, Rafael Oliveira; Ortiz, Vanessa D; Campos, Cristina; Bonetto, Jéssica H P; Fernandes, Tânia R G; Conzatti, Adriana; Siqueira, Rafaela; Tavares, Angela Vicente; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

    2016-02-01

    Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction. PMID:26659365

  7. Limited proteolysis combined with isotope labeling and quantitative LC-MALDI MS for monitoring protein conformational changes: a study on calcium-binding sites of cardiac Troponin C

    International Nuclear Information System (INIS)

    Studies of protein-protein and protein-ligand interactions are important for understanding biological functions of proteins. A new technique based on the partial proteolysis of proteins combined with quantitative mass spectrometry is developed as a means of tracking structural changes after the formation of a protein-ligand complex. In this technique, a protein of interest with and without the binding of a ligand is digested with an enzyme to generate a set of peptides, followed by separation of the peptides by liquid chromatography. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is used to identify chromatographically separated peptides, and locate their sequence alignments in the parent protein. Using an isotopically labeled protein as a sample against an unlabeled protein standard, quantitative information can be gathered. This overcomes the inherent lack of quantitative capability of MALDI MS. The utility of the technique to investigate protein-ligand interactions is demonstrated in a model system involving calcium binding to cardiac Troponin C (cTnC). Using this technique, the general location of the three calcium-binding sites of cTnC can be determined by using several different enzymes to generate overlapping peptide maps of cTnC

  8. Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

    Directory of Open Access Journals (Sweden)

    Planellas Marta

    2012-08-01

    Full Text Available Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS. The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI, in dogs with brachycephalic upper airway obstructive syndrome (BAOS. Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88% had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%, stenotic nares (96%, everted laryngeal saccules (32% and tracheal hypoplasia (29.1%. Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50 had values of CRP > 20 mg/L, 22.9% (11/48 had values of Hp > 3 g/L and 47.8% (22/46 had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

  9. Rapid Diagnosis of acute kidney injury (AKI associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP biomarker

    Directory of Open Access Journals (Sweden)

    Mirbagheri L

    2012-01-01

    Full Text Available Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI. Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour andafter cardiac surgery for detection of L-FABP by Elisa.Results: The results from ELISA test show that the increasing amount of LFABPin urine samples of 4 patients is a diagnostic indicator for AKI. Themean concentration of L-FABP has increased up to 17 times at 8 hours aftercardiac surgery compared to before surgery.Conclusion: according to our findings, we speculated that the urinary L-FABPcan be a reliable and rapid biomarker for diagnosis of acute kidney injury.Key words: Acute Kidney Injury, Liver type Fatty Acid Binding Protein,Cardiac surgery

  10. Counselling issues in familial hypertrophic cardiomyopathy.

    OpenAIRE

    Yu, B.; French, J. A.; Jeremy, R W; French, P; McTaggart, D R; Nicholson, M R; Semsarian, C; Richmond, D R; Trent, R.J.

    1998-01-01

    To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was p...

  11. Reverse actin sliding triggers strong myosin binding that moves tropomyosin

    Energy Technology Data Exchange (ETDEWEB)

    Bekyarova, T.I.; Reedy, M.C.; Baumann, B.A.J.; Tregear, R.T.; Ward, A.; Krzic, U.; Prince, K.M.; Perz-Edwards, R.J.; Reconditi, M.; Gore, D.; Irving, T.C.; Reedy, M.K. (IIT); (EMBL); (Scripps); (Duke); (Prince); (FSU); (MRC); (U. Florence)

    2008-09-03

    Actin/myosin interactions in vertebrate striated muscles are believed to be regulated by the 'steric blocking' mechanism whereby the binding of calcium to the troponin complex allows tropomyosin (TM) to change position on actin, acting as a molecular switch that blocks or allows myosin heads to interact with actin. Movement of TM during activation is initiated by interaction of Ca{sup 2+} with troponin, then completed by further displacement by strong binding cross-bridges. We report x-ray evidence that TM in insect flight muscle (IFM) moves in a manner consistent with the steric blocking mechanism. We find that both isometric contraction, at high [Ca{sup 2+}], and stretch activation, at lower [Ca{sup 2+}], develop similarly high x-ray intensities on the IFM fourth actin layer line because of TM movement, coinciding with x-ray signals of strong-binding cross-bridge attachment to helically favored 'actin target zones.' Vanadate (Vi), a phosphate analog that inhibits active cross-bridge cycling, abolishes all active force in IFM, allowing high [Ca{sup 2+}] to elicit initial TM movement without cross-bridge attachment or other changes from relaxed structure. However, when stretched in high [Ca{sup 2+}], Vi-'paralyzed' fibers produce force substantially above passive response at pCa {approx} 9, concurrent with full conversion from resting to active x-ray pattern, including x-ray signals of cross-bridge strong-binding and TM movement. This argues that myosin heads can be recruited as strong-binding 'brakes' by backward-sliding, calcium-activated thin filaments, and are as effective in moving TM as actively force-producing cross-bridges. Such recruitment of myosin as brakes may be the major mechanism resisting extension during lengthening contractions.

  12. Reverse actin sliding triggers strong myosin binding that moves tropomyosin

    OpenAIRE

    Bekyarova, T. I.; Reedy, M C; Baumann, B. A. J.; Tregear, R T; Ward, A; Krzic, U.; Prince, K.M.; Perz-Edwards, R. J.; Reconditi, M.; Gore, D.; Irving, T C; Reedy, M K

    2008-01-01

    Actin/myosin interactions in vertebrate striated muscles are believed to be regulated by the “steric blocking” mechanism whereby the binding of calcium to the troponin complex allows tropomyosin (TM) to change position on actin, acting as a molecular switch that blocks or allows myosin heads to interact with actin. Movement of TM during activation is initiated by interaction of Ca2+ with troponin, then completed by further displacement by strong binding cross-bridges. We report x-ray evidence...

  13. Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

    Directory of Open Access Journals (Sweden)

    Kamijo-Ikemori A

    2015-08-01

    Full Text Available Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP. Methods: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29. Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05 and 24 hours (P<0.005 after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17, but not in those without cardiovascular events (n=12. The parameter with the largest area under the curve (0.816 for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021. Conclusion: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk

  14. Cyclic AMP-dependent protein kinase phosphorylates residues in the C-terminal domain of the cardiac L-type calcium channel alpha1 subunit.

    Science.gov (United States)

    Leach, R N; Brickley, K; Norman, R I

    1996-06-11

    The molecular basis of the regulation of cardiac L-type calcium channel activity by cAMP-dependent protein kinase (cA-PK) remains unclear. Direct cA-PK-dependent phosphorylation of the bovine ventricular alpha1 subunit in vitro has been demonstrated in microsomal membranes, detergent extracts and partially purified (+)-[3H]PN 200-110 receptor preparations. Two 32P-labeled phosphopeptides, derived from cyanogen bromide cleavage, of 4.7 and 9.5 kDa were immunoprecipitated specifically by site-directed antibodies against the rabbit cardiac alpha1 subunit amino acid sequences 1602-1616 and 1681-1694, respectively, consistent with phosphorylation at the cA-PK consensus sites at Ser(1627) and Ser(1700). No phosphopeptide products consistent with phosphorylation at three other C-terminal cA-PK consensus phosphorylation sites (Ser(1575), Ser(1848) and Ser(1928)) were identified using similar procedures suggesting that these sites are poor substrates for this kinase. Ser(1627) and Ser(1700) may represent sites of cA-PK phosphorylation involved in the physiological regulation of cardiac L-type calcium channel function. PMID:8664319

  15. Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin II Infusion

    OpenAIRE

    Ren, Jingyuan; YANG, MIN; Qi, Guanming; Zheng, Jiao; Jia, LiXin; Cheng, Jizhong; Tian, Cui; Li, Huihua; Lin, Xin; Du, Jie

    2011-01-01

    Background Angiotensin II (Ang II)–induced cardiac remodeling with the underlying mechanisms involving inflammation and fibrosis has been well documented. Cytosolic adaptor caspase recruitment domain 9 (CARD9) has been implicated in the innate immune response. We aimed to examine the role of CARD9 in inflammation and cardiac fibrosis induced by Ang II. Methods Two-month-old CARD9-deficient (CARD9−/−) and wild-type (WT) male mice were infused with Ang II (1,500 ng/kg/min) or saline for 7 days....

  16. Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and Inactivating c-Jun Nuclear Kinase-1 Protein in Type I Diabetes.

    Science.gov (United States)

    Adebiyi, A Olubunmi; Adebiyi, Oluwafeysetan O; Owira, Peter M O

    2016-02-01

    Cardiac hypertrophy (CH) in type 1 diabetes mellitus is attributed to increased oxidative stress-associated activation of c-Jun Nuclear Kinase (JNK). We investigated the effects of naringin on hyperglycemia-associated oxidative stress, activation of JNK-1, and CH. Male Sprague-Dawley rats (225-250 g) (n = 7) were divided into 6 groups. Groups I and II were orally treated with distilled water [3.0 mL/kg body weight/day (BW)] and naringin (50 mg/kg BW), respectively. Groups III-VI were rendered diabetic by a single intraperitoneal injection of 65 mg/kg BW of streptozotocin. Groups III, IV, and V were further treated with insulin (4.0 I.U, s.c, twice daily), naringin (50 mg/kg BW), and ramipril (3.0 mg/kg BW), respectively. After 56 days, the animals were sacrificed and then plasma and cardiac tissues obtained for further analysis. Naringin treatment of diabetic rats significantly reversed oxidative stress, lipid peroxidation, proteins oxidation, CH indices, and JNK protein activation compared with untreated diabetic animals. Our results do suggest that naringin mitigates CH by inhibiting oxidative stress leading to inactivation of JNK-1. Naringin supplements could therefore ameliorate CH in diabetic patients. PMID:26421421

  17. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

    Directory of Open Access Journals (Sweden)

    JanGlatz

    2012-09-01

    Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

  18. Targeted disruption of the mouse Csrp2 gene encoding the cysteine- and glycine-rich LIM domain protein CRP2 result in subtle alteration of cardiac ultrastructure

    Directory of Open Access Journals (Sweden)

    Stoll Doris

    2008-08-01

    Full Text Available Abstract Background The cysteine and glycine rich protein 2 (CRP2 encoded by the Csrp2 gene is a LIM domain protein expressed in the vascular system, particularly in smooth muscle cells. It exhibits a bimodal subcellular distribution, accumulating at actin-based filaments in the cytosol and in the nucleus. In order to analyze the function of CRP2 in vivo, we disrupted the Csrp2 gene in mice and analysed the resulting phenotype. Results A ~17.3 kbp fragment of the murine Csrp2 gene containing exon 3 through 6 was isolated. Using this construct we confirmed the recently determined chromosomal localization (Chromosome 10, best fit location between markers D10Mit203 proximal and D10Mit150 central. A gene disruption cassette was cloned into exon 4 and a mouse strain lacking functional Csrp2 was generated. Mice lacking CRP2 are viable and fertile and have no obvious deficits in reproduction and survival. However, detailed histological and electron microscopic studies reveal that CRP2-deficient mice have subtle alterations in their cardiac ultrastructure. In these mice, the cardiomyocytes display a slight increase in their thickness, indicating moderate hypertrophy at the cellular level. Although the expression of several intercalated disc-associated proteins such as β-catenin, N-RAP and connexin-43 were not affected in these mice, the distribution of respective proteins was changed within heart tissue. Conclusion We conclude that the lack of CRP2 is associated with alterations in cardiomyocyte thickness and hypertrophy.

  19. Interaction of MIF Family Proteins in Myocardial Ischemia/Reperfusion Damage and Their Influence on Clinical Outcome of Cardiac Surgery Patients

    Science.gov (United States)

    Rex, Steffen; Goetzenich, Andreas; Kraemer, Sandra; Emontzpohl, Christoph; Soppert, Josefin; Averdunk, Luisa; Sun, Yu; Rossaint, Rolf; Lue, Hongqi; Huang, Caleb; Song, Yan; Pantouris, Georgios; Lolis, Elias; Leng, Lin; Schulte, Wibke; Bucala, Richard; Weber, Christian

    2015-01-01

    Abstract Aims: Cardiac surgery involves myocardial ischemia/reperfusion (I/R) with potentially deleterious consequences. Macrophage migration inhibitory factor (MIF) is a stress-regulating chemokine-like cytokine that protects against I/R damage, but functional links with its homolog, d-dopachrome tautomerase (MIF-2), and the circulating soluble receptor CD74 (sCD74) are unknown. In this study, we investigate the role of MIF, MIF-2, sCD74, and MIF genotypes in patients scheduled for elective single or complex surgical procedures such as coronary artery bypass grafting or valve replacement. Results: MIF and MIF-2 levels significantly increased intraoperatively, whereas measured sCD74 decreased correspondingly. Circulating sCD74/MIF complexes were detectable in 50% of patients and enhanced MIF antioxidant activity. Intraoperative MIF levels were independently associated with a reduced risk for the development of atrial fibrillation (AF) (odds ratio 0.99 [0.98–1.00]; p=0.007). Circulating levels of MIF-2, but not MIF, were associated with an increased frequency of organ dysfunction and predicted the occurrence of AF (area under the curve [AUC]=0.663; p=0.041) and pneumonia (AUC=0.708; p=0.040). Patients with a high-expression MIF genotype exhibited a reduced incidence of organ dysfunction compared with patients with low-expression MIF genotypes (3 vs. 25; p=0.042). Innovation: The current study comprehensively highlights the kinetics and clinical relevance of MIF family proteins and the MIF genotype in cardiac surgery patients. Conclusion: Our findings suggest that increased MIF levels during cardiac surgery feature organ-protective properties during myocardial I/R, while the soluble MIF receptor, sCD74, may enhance MIF antioxidant activity. In contrast, high MIF-2 levels are predictive of the development of organ dysfunction. Importantly, we provide first evidence for a gene–phenotype relationship between variant MIF alleles and clinical outcome in cardiac

  20. The Role of Inhibitory G Proteins and Regulators of G Protein Signaling in the in vivo Control of Heart Rate and Predisposition to Cardiac Arrhythmias.

    Science.gov (United States)

    Ang, Richard; Opel, Aaisha; Tinker, Andrew

    2012-01-01

    Inhibitory heterotrimeric G proteins and the control of heart rate. The activation of cell signaling pathways involving inhibitory heterotrimeric G proteins acts to slow the heart rate via modulation of ion channels. A large number of Regulators of G protein signalings (RGSs) can act as GTPase accelerating proteins to inhibitory G proteins and thus it is important to understand the network of RGS\\G-protein interaction. We will review our recent findings on in vivo heart rate control in mice with global genetic deletion of various inhibitory G protein alpha subunits. We will discuss potential central and peripheral contributions to the phenotype and the controversies in the literature. PMID:22783193

  1. Activation of extracellular signal-regulated kinase during silibinin-protected, isoproterenol-induced apoptosis in rat cardiac myocytes is tyrosine kinase pathway-mediated and protein kinase C-dependent

    Institute of Scientific and Technical Information of China (English)

    Bei ZHOU; Li-jun WU; Shin-ichi TASHIRO; Satoshi ONODERA; Fumiaki UCHIUMI; Takashi IKEJIMA

    2007-01-01

    Aim: To investigate the mechanism of silibinin-protected isoproterenol-induced apoptosis in rat cardiac myocytes.Methods: The viability of rat cardiac myocytes was measured by MTT method. The apoptotic ratio was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Protein kinase C (PKC) activity assay was carried out according to the instructions of the PepTag non-radioactive protein kinase C assay kit. Western blot analysis was used to evaluate the level of Ras, Raf-1 and mitogen-activated protein kinase (MAPK) expression.Results: The protective effects of silibinin were significantly sup-pressed by inhibitors, including genistein, manumycin A and GW5074 [inhibitors for protein tyrosine kinases (PTK), Ras and Raf- 1, respectively]. The exposure of rat cardiac myocytes to isoproterenol alone caused decreased PKC activity, which was prevented by pretreatment with silibinin dose-dependently. Simultaneously,the increased expression of Ras and Raf-1 activated by silibinin were blocked by the PKC inhibitor, stauroporine. In addition, the extracellularly responsive kinase (ERK) inhibitor, PD98059, suppressed silibinin-protected apoptosis, whereas the p38 MAPK inhibitor, SB203580, protected cardiac myocytes from isoproterenol-induced injury, and the c-Jun N-terminal kinase (JNK) inhibitor, SP600125 had no protective effects. Furthermore, Western blot analysis showed that the expres-sion of phosphorylated ERK was increased by silibinin, the expression of phos-phorylated p38 MAPK was decreased and total ERK, p38, JNK and phosphory-lated JNK MAPK did not change after treatment with both isoproterenol and silibinin. Furthermore, pretreatment of cardiac myocyte with PKC, Ras and Raf inhibitors significantly blocked ERK phosphorylation.Conclusion: Silibinin is suggested to protect isoproterenol-induced rat cardiac myocyte apoptosis by activating the tyrosine kinase pathway, PKC and MAPK pathways.

  2. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  3. 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 ...

  4. Cardiac sarcoidosis

    OpenAIRE

    Costello BT; Nadel J.; Taylor AJ

    2016-01-01

    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 syst...

  5. REGULATION OF CARDIAC AND SKELETAL MUSCLE PROTEIN SYNTHESIS BY INDIVIDUAL BRANCHED-CHAIN AMINO ACIDS IN NEONATAL PIGS

    Science.gov (United States)

    Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an enhanced sensitivity of protein synthesis to the postprandial rise in amino acids. An increase in leucine alone stimulates protein synthesis in skeletal muscle of the neonatal pig; however, the effect of isoleucine and...

  6. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  7. Aldehyde dehydrogenase type 2 activation by adenosine and histamine inhibits ischemic norepinephrine release in cardiac sympathetic neurons: mediation by protein kinase Cε.

    Science.gov (United States)

    Robador, Pablo A; Seyedi, Nahid; Chan, Noel Yan-Ki; Koda, Kenichiro; Levi, Roberto

    2012-10-01

    During myocardial ischemia/reperfusion, lipid peroxidation leads to the formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. Because excessive norepinephrine release in the heart is a pivotal arrhythmogenic mechanism, we hypothesized that neuronal ALDH2 activation might diminish ischemic norepinephrine release. Incubation of cardiac sympathetic nerve endings with acetaldehyde, at concentrations achieved in myocardial ischemia, caused a concentration-dependent increase in norepinephrine release. A major increase in norepinephrine release also occurred when sympathetic nerve endings were incubated in hypoxic conditions. ALDH2 activation substantially reduced acetaldehyde- and hypoxia-induced norepinephrine release, an action prevented by inhibition of ALDH2 or protein kinase Cε (PKCε). Selective activation of G(i/o)-coupled adenosine A(1), A(3), or histamine H(3) receptors markedly inhibited both acetaldehyde- and hypoxia-induced norepinephrine release. These effects were also abolished by PKCε and/or ALDH2 inhibition. Moreover, A(1)-, A(3)-, or H(3)-receptor activation increased ALDH2 activity in a sympathetic neuron model (differentiated PC12 cells stably transfected with H(3) receptors). This action was prevented by the inhibition of PKCε and ALDH2. Our findings suggest the existence in sympathetic neurons of a protective pathway initiated by A(1)-, A(3)-, and H(3)-receptor activation by adenosine and histamine released in close proximity of these terminals. This pathway comprises the sequential activation of PKCε and ALDH2, culminating in aldehyde detoxification and inhibition of hypoxic norepinephrine release. Thus, pharmacological activation of PKCε and ALDH2 in cardiac sympathetic nerves may have significant protective effects by alleviating norepinephrine-induced life-threatening arrhythmias that

  8. Differential expression of cardiac muscle mitochondrial matrix proteins in broilers from ascites-resistant and susceptible lines.

    Science.gov (United States)

    Cisar, C R; Balog, J M; Anthony, N B; Donoghue, A M

    2005-05-01

    Ascites is a metabolic disorder of modern broilers that is distinguished by cardiopulmonary insufficiency in the face of intense oxygen demands of rapidly growing tissues. Broilers with ascites exhibit sustained elevation of pulmonary arterial pressure and right ventricular hypertrophy, the end result of which is heart failure. It has been shown that mitochondrial function is impaired in broilers with ascites. In the current study, mitochondrial matrix protein levels were compared between ascites-resistant line broilers and ascites-susceptible line broilers with and without ascites using two-dimensional (2-D) gel electrophoresis. One hundred seventy-two protein spots were detected on the gels, and 9 of the spots were present at different levels in the 4 groups of broilers. These 9 protein spots were selected for identification by mass spectrometry. Two of the spots were found to contain single mitochondrial matrix proteins. Both mitochondrial matrix proteins, the dihydrolipoamide succinyltransferase component of the 2-oxoglutarate dehydrogenase complex and the alpha-subunit of mitochondrial trifunctional enzyme, were present at higher levels in ascites-resistant line broilers with ascites in the present study. The elevated levels of 2 key proteins in aerobic metabolism in ascites-resistant line broilers with ascites observed in the present study suggests that the mitochondria of broilers with this disease may respond inappropriately to hypoxia. PMID:15913181

  9. Glucagon-like peptide-1 enhances cardiac L-type Ca2+ currents via activation of the cAMP-dependent protein kinase A pathway

    Directory of Open Access Journals (Sweden)

    Jaye Deborah A

    2011-01-01

    Full Text Available Abstract Background Glucagon-like peptide-1 (GLP-1 is a hormone predominately synthesized and secreted by intestinal L-cells. GLP-1 modulates multiple cellular functions and its receptor agonists are now used clinically for diabetic treatment. Interestingly, preclinical and clinical evidence suggests that GLP-1 agonists produce beneficial effects on dysfunctional hearts via acting on myocardial GLP-1 receptors. As the effects of GLP-1 on myocyte electrophysiology are largely unknown, this study was to assess if GLP-1 could affect the cardiac voltage-gated L-type Ca2+ current (ICa. Methods The whole-cell patch clamp method was used to record ICa and action potentials in enzymatically isolated cardiomyocytes from adult canine left ventricles. Results Extracellular perfusion of GLP-1 (7-36 amide at 5 nM increased ICa by 23 ± 8% (p Ca; however, the increase in ICa was abolished if Exendin (9-39 was pre-applied 5 min prior to GLP-1 administration. Intracellular dialysis with a protein kinase A inhibitor also blocked the GLP-1-enhanced ICa. In addition, GLP-1 at 5 nM prolonged the durations of the action potentials by 128 ± 36 ms (p p Conclusions Our data demonstrate that GLP-1 enhances ICa in canine cardiomyocytes. The enhancement of ICa is likely via the cAMP-dependent protein kinase A mechanism and may contribute, at least partially, to the prolongation of the action potential duration.

  10. Heterologous expression of the bovine cardiac fatty acid-binding protein (H-FABP) in the yeast Yarrowia lipolytica: biochemical and physiological studies

    International Nuclear Information System (INIS)

    Little is known about the metabolic significance of fatty acid-binding proteins (FABPs) in lipid metabolism in vivo. The bovine cardiac FABP (H-FABP) was expressed in the yeast Y. lipolytica to investigate its function in vivo. An expression system was established using homologous LEU2 -transcription signals and characterized by applying E.coli beta-glucuronidase (beta-GUS). This marker represents a new and highly sensitive reporter system in Y. lipolytica. The heterologous H-FABP made up 0.05-0.1% of the yeast cytosolic protein. The heterologous H-FABP reacted with an antibody raised against the authentic H-FABP and had the identical size of 14 kDa. Despite its capacity to bind fatty acids (FA) in vitro, it did not affect the intracellular partitioning of incorporated radioactively labeled palmitic or oleic acid between phospholipids (PL), the free fatty acid fraction and triacylglycerols (TAG). Uptake, desaturation and beta-oxidation of the particular FA, as well as de novo biosynthesis of FA were unaffected. The investigations on intracellular partitioning of FA demonstrated different incorporation characteristics of FA in dependence of growth and temperature conditions, indicating selective mechanisms in membrane assembly. Furthermore, data suggest modification (desaturation/elongation) of FA in the PL-fraction followed by transesterification into the TAG. The investigations allowed new insights into regulatory aspects of lipid metabolism in Y. lipolytica. (author)

  11. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  12. 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.

  13. Cardiac sarcoidosis

    Science.gov (United States)

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  14. The study of mutations presence in exons 27 and 29 of MYBPC3 gene by PCR-SSCP/HA method in patients with hypertrophy cardiomyopathy in Chaharmahal and Bakhtiari province

    OpenAIRE

    Saeidi M; Doosti A; Parchami Bajue S; Hashemzadeh Chaleshtori M

    2016-01-01

    Background and aims: Hypertrophy cardiomyopathy (HCM) is the most common type of heart disease with monogenic inheritance distinguished by thickening of left ventricle, contractile dysfunction and potentially fatal arrhythmias. Great progress in clarifying the genetic basis of HCM obtained. It was identified more than 900 unique mutations in 20 genes. Mutations in the gene MYBPC3 (which encodes the cardiac Myosin binding protein C) are about 40% of clinical cases. This study aimed to investig...

  15. Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism.

    Science.gov (United States)

    Park, Chi-Yeon; Choi, Seung-Cheol; Kim, Jong-Ho; Choi, Ji-Hyun; Joo, Hyung Joon; Hong, Soon Jun; Lim, Do-Sun

    2016-01-01

    Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31- human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31- CSCs(hTERT)), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCs(hTERT) sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31- CSCs(hTERT) were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31- CSCs(hTERT) conditioned medium (CM). Sca-1+/CD31- CSCs(hTERT) CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCs(hTERT) CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCs(hTERT) exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCs(hTERT) CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field. PMID:27231894

  16. Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ.

    Science.gov (United States)

    Lin, Ying-Hsi; Warren, Chad M; Li, Jieli; McKinsey, Timothy A; Russell, Brenda

    2016-08-01

    The mechanotransduction signaling pathways initiated in heart muscle by increased mechanical loading are known to lead to long-term transcriptional changes and hypertrophy, but the rapid events for adaptation at the sarcomeric level are not fully understood. The goal of this study was to test the hypothesis that actin filament assembly during cardiomyocyte growth is regulated by post-translational modifications (PTMs) of CapZβ1. In rapidly hypertrophying neonatal rat ventricular myocytes (NRVMs) stimulated by phenylephrine (PE), two-dimensional gel electrophoresis (2DGE) of CapZβ1 revealed a shift toward more negative charge. Consistent with this, mass spectrometry identified CapZβ1 phosphorylation on serine-204 and acetylation on lysine-199, two residues which are near the actin binding surface of CapZβ1. Ectopic expression of dominant negative PKCɛ (dnPKCɛ) in NRVMs blunted the PE-induced increase in CapZ dynamics, as evidenced by the kinetic constant (Kfrap) of fluorescence recovery after photobleaching (FRAP), and concomitantly reduced phosphorylation and acetylation of CapZβ1. Furthermore, inhibition of class I histone deacetylases (HDACs) increased lysine-199 acetylation on CapZβ1, which increased Kfrap of CapZ and stimulated actin dynamics. Finally, we show that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. Taken together, this dual regulation through phosphorylation and acetylation of CapZβ1 provides a novel model for the regulation of myofibril growth during cardiac hypertrophy. PMID:27185186

  17. Folic Acid Reverses Nitric Oxide Synthase Uncoupling and Prevents Cardiac Dysfunction in Insulin Resistance: Role of Ca2+/Calmodulin-Activated Protein Kinase II

    OpenAIRE

    Roe, Nathan D.; He, Emily Y.; Wu, Zhenbiao; Ren, Jun

    2013-01-01

    Nitric oxide synthase (NOS) may be uncoupled to produce superoxide rather than nitric oxide (NO) under pathological conditions such as diabetes mellitus and insulin resistance, leading to cardiac contractile anomalies. Nonetheless, the role of NOS uncoupling in insulin resistance-induced cardiac dysfunction remains elusive. Given that folic acid may produce beneficial effect for cardiac insufficiency partially through its NOS recoupling capacity, this study was designed to evaluate the effect...

  18. Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events

    Directory of Open Access Journals (Sweden)

    Klauß, Volker

    2009-05-01

    Full Text Available Background: In a substantial portion of patients (= 25% with coronary heart disease (CHD, a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-fatal myocardial infarction. Research question: Does the additional information gained through the measurement of hs-CRP in asymptomatic patients lead to a clinically relevant improvement in risk prediction as compared to risk prediction based on traditional risk factors and is this cost-effective? Methods: A literature search of the electronic databases of the German Institute of Medical Documentation and Information (DIMDI was conducted. Selection, data extraction, assessment of the study-quality and synthesis of information was conducted according to the methods of evidence-based medicine. Results: Eight publications about predictive value, one publication on the clinical efficacy and three health-economic evaluations were included. In the seven study populations of the prediction studies, elevated CRP-levels were almost always associated with a higher risk of cardiovascular events and non-fatal myocardial infarctions or cardiac death and severe cardiovascular events. The effect estimates (odds ratio (OR, relative risk (RR, hazard ratio (HR, once adjusted for traditional risk factors, demonstrated a moderate, independent association between hs-CRP and cardiac and cardiovascular events that fell in the range of 0.7 to 2.47. In six of the seven studies, a moderate increase in the area under the curve (AUC could be detected by adding hs-CRP as a predictor to regression models in addition to established risk factors though in three cases this was not

  19. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  20. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc

    OpenAIRE

    Heineke, Joerg; Ruetten, Hartmut; Willenbockel, Christian; Gross, Sandra C.; Naguib, Marian; Schaefer, Arnd; Kempf, Tibor; Hilfiker-Kleiner, Denise; Caroni, Pico; Kraft, Theresia; Kaiser, Robert A.; Molkentin, Jeffery D; Drexler, Helmut; Wollert, Kai C.

    2005-01-01

    Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause for heart failure. Molecular modifiers of the remodeling process remain poorly defined. Patients with heart failure after MI have reduced LV expression levels of muscle LIM protein (MLP), a component of the sarcomeric Z-disk that is involved in the integration of stress signals in cardiomyocytes. By using heterozygous MLP mutant (MLP+/—) mice, we explored the role of MLP in post-MI remodeling. LV dimens...

  1. Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

    OpenAIRE

    Kamijo-Ikemori A; Hashimoto N; Sugaya T; Matsui K; Hisamichi M; Shibagaki Y; Miyake F; Kimura K

    2015-01-01

    Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM) induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP) increas...

  2. Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

    Directory of Open Access Journals (Sweden)

    Jong Wook Song

    2016-01-01

    Full Text Available Activation of peroxisome proliferator-activated receptor α (PPARα confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP. Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, P<0.05. During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05. H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.

  3. Detection of cardiac biomarker proteins using a disposable based on a molecularly imprinted polymer grafted onto graphite

    International Nuclear Information System (INIS)

    A low-cost disposable was developed for rapid detection of the protein biomarker myoglobin (Myo) as a model analyte. A screen printed electrode was modified with a molecularly imprinted material grafted on a graphite support and incorporated in a matrix composed of poly(vinyl chloride) and the plasticizer o-nitrophenyloctyl ether. The protein-imprinted material (PIM) was produced by growing a reticulated polymer around a protein template. This is followed by radical polymerization of 4-styrenesulfonic acid, 2-aminoethyl methacrylate hydrochloride, and ethylene glycol dimethacrylate. The polymeric layer was then covalently bound to the graphitic support, and Myo was added during the imprinting stage to act as a template. Non-imprinted control materials (CM) were also prepared by omitting the Myo template. Morphological and structural analysis of PIM and CM by FTIR, Raman, and SEM/EDC microscopies confirmed the modification of the graphite support. The analytical performance of the SPE was assessed by square wave voltammetry. The average limit of detection is 0.79 μg of Myo per mL, and the slope is −0.193 ± 0.006 μA per decade. The SPE-CM cannot detect such low levels of Myo but gives a linear response at above 7.2 μg · mL−1, with a slope of −0.719 ± 0.02 μA per decade. Interference studies with hemoglobin, bovine serum albumin, creatinine, and sodium chloride demonstrated good selectivity for Myo. The method was successfully applied to the determination of Myo urine and is conceived to be a promising tool for screening Myo in point-of-care patients with ischemia. (author)

  4. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery

    OpenAIRE

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M; Lorente, Juan; Cerón, José J.; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determi...

  5. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  6. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  7. Troponin Ⅰ,cardiac diastolic dysfunction and restrictive cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Xu-pei HUANG; Jian-feng DU

    2004-01-01

    Cardiomyopathies are diseases of heart muscle that are associated with cardiac dysfunction. Molecular genetic studies performed to date have demonstrated that the damage or mutations in several sarcomeric contractile protein genes are associated with the development of the diseases. In this review, cardiac troponin Ⅰ, one of the sarcomeric thin filament protein, will be discussed regarding its role in cardiac function, its deficiency-related diastolic dysfunction, and the mutation of this protein-mediated restrictive cardiomyopathy.

  8. Relationship of High Sensitivity C-Reactive Protein with Cardiac Biomarkers in Patients Presenting with Acute Coronary Syndrome

    International Nuclear Information System (INIS)

    Objective: To determine high sensitivity C-reactive protein (hsCRP) levels in patients with acute myocardial infarction (AMI) and its correlation with classical enzyme markers of myocardial damage. Study Design: Observational study. Place and Duration of Study: Department of Emergency Medicine at King Khalid University Hospital, King Saud University, Riyadh and Department of Physiology, from August 2010 to December 2011. Methodology: Consecutive eligible patients with either ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) who were admitted to the Emergency Department of King Khalid University Hospital were recruited. A total of 71 subjects were finally selected for the study. The hsCRP, Troponin I (Trop I), creatine kinase myocardial bound (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) concentrations of all patients with an acute myocardial infarction (AMI) were measured. Results: Among all patients 34 (47.9%) patients had diabetes mellitus, 21 (29.6%) were hypertensive, and 16 (22.5%) had no associated illness. Patients with STEMI had significantly higher levels of CKMB (p=0.0348), LDH (p=0.0471) and hsCRP (p=0.0231) compared to NSTEMI patients. While the differences were non-significant for Trop I (p=0.7022), AST (p=0.9729) and Lp(a) (p=0.5985). Spearman's correlations revealed that CRP correlated significantly with Trop I, CK-MB and LDH. There was a significant predictive relationship of hsCRP with Trop I, LDH and CK-MB while with AST it was nonsignificant. Conclusion: High sensitivity CRP levels is a significant predictor of standard markers for myocardial damage and it may be a useful prognostic marker in acute coronary syndromes. (author)

  9. Human umbilical cord blood mononuclear cells activate the survival protein Akt in cardiac myocytes and endothelial cells that limits apoptosis and necrosis during hypoxia.

    Science.gov (United States)

    Henning, Robert J; Dennis, Steve; Sawmiller, Darrell; Hunter, Lorynn; Sanberg, Paul; Miller, Leslie

    2012-06-01

    We have previously reported that human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic, mesenchymal, and endothelial stem cells, can significantly reduce acute myocardial infarction size. To determine the mechanism whereby HUCBC increase myocyte and vascular endothelial cell survival, we treated cardiac myocytes and coronary artery endothelial cells in separate experiments with HUCBC plus culture media or culture media alone and subjected the cells to 24 h of hypoxia or normoxia. We then determined in myocytes and endothelial cells activation of the cell survival protein Akt by Western blots. We also determined in these cells apoptosis by annexin V staining and necrosis by propidium iodide staining. Thereafter, we inhibited with API, a specific and sensitive Akt inhibitor, Akt activation in myocytes and endothelial cells cultured with HUCBC during hypoxia and determined cell apoptosis and necrosis. In cells cultured without HUCBC, hypoxia only slightly activated Akt. Moreover, hypoxia increased myocyte apoptosis by ≥ 226% and necrosis by 58% in comparison with myocytes in normoxia. Hypoxic treatment of endothelial cells without HUCBC increased apoptosis by 94% and necrosis by 59%. In contrast, hypoxia did not significantly affect HUCBC. Moreover, in myocyte + HUCBC cultures in hypoxia, HUCBC induced a ≥ 135% increase in myocyte phospho-Akt. Akt activation decreased myocyte apoptosis by 76% and necrosis by 35%. In endothelial cells, HUCBC increased phospho-Akt by 116%. HUCBC also decreased endothelial cell apoptosis by 58% and necrosis by 42%. Inhibition of Akt with API in myocytes and endothelial cells cultured with HUCBC during hypoxia nearly totally prevented the HUCBC-induced decrease in apoptosis and necrosis. We conclude that HUCBC can significantly decrease hypoxia-induced myocyte and endothelial cell apoptosis and necrosis by activating Akt in these cells and in this manner HUCBC can limit myocardial ischemia and injury. PMID

  10. Observation of μs time-scale protein dynamics in the presence of Ln3+ ions: application to the N-terminal domain of cardiac troponin C

    International Nuclear Information System (INIS)

    The microsecond time-scale motions in the N-terminal domain of cardiac troponin C (NcTnC) loaded with lanthanide ions have been investigated by means of a 1HN off-resonance spin-lock experiment. The observed relaxation dispersion effects strongly increase along the series of NcTnC samples containing La3+, Ce3+, and Pr3+ ions. This rise in dispersion effects is due to modulation of long-range pseudocontact shifts by μs time-scale dynamics. Specifically, the motion in the coordination sphere of the lanthanide ion (i.e. in the NcTnC EF-hand motif) causes modulation of the paramagnetic susceptibility tensor which, in turn, causes modulation of pseudocontact shifts. It is also probable that opening/closing dynamics, previously identified in Ca2+-NcTnC, contributes to some of the observed dispersions. On the other hand, it is unlikely that monomer-dimer exchange in the solution of NcTnC is directly responsible for the dispersion effects. Finally, on-off exchange of the lanthanide ion does not seem to play any significant role. The amplification of dispersion effects by Ln3+ ions is a potentially useful tool for studies of μs-ms motions in proteins. This approach makes it possible to observe the dispersions even when the local environment of the reporting spin does not change. This happens, for example, when the motion involves a 'rigid' structural unit such as individual α-helix. Even more significantly, the dispersions based on pseudocontact shifts offer better chances for structural characterization of the dynamic species. This method can be generalized for a large class of applications via the use of specially designed lanthanide-binding tags

  11. 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 contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  12. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  13. Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.

    Science.gov (United States)

    Chang, Wenguang; Zhang, Ming; Meng, Zhaojie; Yu, Yang; Yao, Fan; Hatch, Grant M; Chen, Li

    2015-12-15

    Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy. PMID:26522928

  14. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  15. 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 C

  16. Fullerene mediates proliferation and cardiomyogenic differentiation of adipose-derived stem cells via modulation of MAPK pathway and cardiac protein expression

    Directory of Open Access Journals (Sweden)

    Hao T

    2016-01-01

    Full Text Available Tong Hao,1,2,* Jin Zhou,2,* Shuanghong Lü,3,* Boguang Yang,2,4 Yan Wang,2 Wancai Fang,2,4 Xiaoxia Jiang,2 Qiuxia Lin,2 Junjie Li,2 Changyong Wang1,21School of Life Science and Technology, Harbin Institute of Technology, Harbin, 2Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 3Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, 4Department of Polymer Science, Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Zero-dimensional fullerenes can modulate the biological behavior of a variety of cell lines. However, the effects and molecular mechanisms of proliferation and cardiomyogenic differentiation in brown adipose-derived stem cells (BADSCs are still unclear. In this study, we report the initial biological effects of fullerene-C60 on BADSCs at different concentrations. Results suggest that fullerene-C60 has no cytotoxic effects on BADSCs even at a concentration of 100 µg/mL. Fullerene-C60 improves the MAPK expression level and stem cell survival, proliferation, and cardiomyogenesis. Further, we found that the fullerene-C60 modulates cardiomyogenic differentiation. Fullerene-C60 improves the expression of cardiomyocyte-specific proteins (cTnT and α-sarcomeric actinin. At elevated concentration, fullerene-C60 reduces the incidence of diminished spontaneous cardiac differentiation of BADSCs with time. At the genetic level, fullerene-C60 (5 µg/mL also improves the expression of cTnT. In addition, fullerene-C60 promotes the formation of gap junction among cells. These findings have important implications for clinical application of fullerenes in the treatment of myocardial infarction.Keywords: C60, BADSCs, molecular

  17. Aldehyde Dehydrogenase Type 2 Activation by Adenosine and Histamine Inhibits Ischemic Norepinephrine Release in Cardiac Sympathetic Neurons: Mediation by Protein Kinase Cε

    OpenAIRE

    Robador, Pablo A.; Seyedi, Nahid; Chan, Noel Yan-Ki; Koda, Kenichiro; Levi, Roberto

    2012-01-01

    During myocardial ischemia/reperfusion, lipid peroxidation leads to the formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. Because excessive norepinephrine release in the heart is a pivotal arrhythmogenic mechanism, we hypothesized that neuronal ALDH2 activation might diminish ischemic norepinephrine release. Incubation of cardiac sym...

  18. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  19. Study the presence of mutations in exons 30 and 33 MYBPC3 gene in patients with hypertrophic cardiomyopathy by PCR-SSCP/HA method in Chaharmahal and Bakhtiari

    OpenAIRE

    Sheikhshahrokh A; Hashemzadeh Chaleshteri M; Doosti A; Parchami Barjoui S

    2016-01-01

    Background and aims: HCM is a common form of hereditary heart disease with Mendelian inheritance that is a frequent cause of sudden cardiac death in the people younger than 35 years. In more than 50% of cases the cause of HCM identified as gene mutations. Mutations in the gene MYBPC3 (which encodes the cardiac Myosin binding protein C) are about 40% of clinical cases. This study was aimed to investigate the presence of mutations in exons 30 and 33 MYBPC3 gene in patients with hypertrophic car...

  20. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  1. Review Article of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jittiporn PURATTANAMAL

    2010-06-01

    Full Text Available Cardiac amyloidosis is a term that means the deposit of abnormal proteins in the myocardium leading to global thickening of the heart walls. The clinical character is that of infiltrative cardiomyopathy. AL amyloidosis is the most common type that involves cardiac failure. Cardiac amyloid precedes clinical congestive heart failure, especially right-sided heart failure. Laboratory investigations have identified the amyloid fibril proteins deposited in the organ tissues. Immunofixation tests are the most sensitive that recognize the paraprotein mean light chain protein or immunoglobulin subtype deposit. Prognosis is poor if AL amyloidosis is untreated. Treatment of systemic involvement in AL amyloidosis is via chemotherapy such as melphalan and prednisolone. UK experts have reported the results of treatment in AL amyloidosis. Regardless of the use of adjunctive chemotherapy, the five-year survival after heart transplantation was generally poorer for AL (20 % at five years, but similar for non-AL amyloidosis (64 % at five years, than heart transplants in other cases. Progression of the systemic disease contributed to increased mortality. A specific treatment that increases the chances of survival is unknown.

  2. Cardiac extracellular matrix proteomics: Challenges, techniques, and clinical implications.

    Science.gov (United States)

    Chang, Chia Wei; Dalgliesh, Ailsa J; López, Javier E; Griffiths, Leigh G

    2016-01-01

    Extracellular matrix (ECM) has emerged as a dynamic tissue component, providing not only structural support, but also functionally participating in a wide range of signaling events during development, injury, and disease remodeling. Investigation of dynamic changes in cardiac ECM proteome is challenging due to the relative insolubility of ECM proteins, which results from their macromolecular nature, extensive post-translational modification (PTM), and tendency to form protein complexes. Finally, the relative abundance of cellular and mitochondrial proteins in cardiac tissue further complicates cardiac ECM proteomic approaches. Recent developments of various techniques to enrich and analyze ECM proteins are playing a major role in overcoming these challenges. Application of cardiac ECM proteomics in disease tissues can further provide spatial and temporal information relevant to disease diagnosis, prognosis, treatment, and engineering of therapeutic candidates for cardiac repair and regeneration. PMID:26200932

  3. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  4. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  5. Transthyretin Cardiac Amyloidoses in Older North Americans

    OpenAIRE

    Dharmarajan, Kumar; Maurer, Mathew S.

    2012-01-01

    The amyloidoses are a group of hereditary or acquired disorders caused by the extracellular deposition of insoluble protein fibrils that impair tissue structure and function. All amyloidoses result from protein misfolding, a common mechanism for disorders in older persons including Alzheimer's disease and Parkinson's disease. Cardiac amyloidoses in the elderly are most often caused by abnormalities in the protein transthyretin (TTR), a serum transporter of thyroxine and retinol. Mutations in ...

  6. Recent advances in the diagnosis and management of cardiac amyloidosis.

    Science.gov (United States)

    Sher, Taimur; Gertz, Morie A

    2014-01-01

    The heart is commonly involved in various forms of amyloidosis and cardiomyopathy is a major cause of morbidity and mortality in these patients. Diagnosis of cardiac amyloidosis is often delayed due to nonspecific presenting symptoms and failure to recognize early signs of amyloid heart disease on routine cardiac imaging. Treatment of cardiac amyloidosis depends upon the type of amyloid protein. Systemic chemotherapy with or without stem cell transplantation is used to treat immunoglobulin-related amyloidosis and liver transplantation is used for familial transthyretin amyloidosis in select patients. Clinical trials with siRNA for the treatment of transthyretin amyloid cardiomyopathies and amyloid protein stabilizers are ongoing. Prognosis depends on the type of amyloid protein with poorer outcomes noted in immunoglobulin light-chain amyloidosis. Supportive care forms the cornerstone of management and advancements in cardiac imaging and proteomics are expected to positively impact our ability to diagnose, prognosticate and treat cardiac amyloidosis. PMID:24344669

  7. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    JonasSDe Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  8. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  9. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    C.A. Remme; C.R. Bezzina

    2010-01-01

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

  10. Angiotensin II type 1 receptors stimulate protein synthesis in human cardiac fibroblasts via a Ca2+-sensitive PKC-dependent tyrosine kinase pathway

    DEFF Research Database (Denmark)

    Hou, M; Pantev, E; Möller, S;

    2000-01-01

    ) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by...

  11. Preoperative cardiac risk management

    OpenAIRE

    Vidaković Radosav; Poldermans Don; Nešković Aleksandar N.

    2011-01-01

    Approximately 100 million people undergo noncardiac surgery annually worldwide. It is estimated that around 3% of patients undergoing noncardiac surgery experience a major adverse cardiac event. Although cardiac events, like myocardial infarction, are major cause of perioperative morbidity or mortality, its true incidence is difficult to assess. The risk of perioperative cardiac complications depends mainly on two conditions: 1) identified risk factors, and 2) the type of the surgical p...

  12. Cardiac troponin: an emerging cardiac biomarker in animal health

    Directory of Open Access Journals (Sweden)

    Vishal V. Undhad

    Full Text Available Analysis of cardiac troponin I (cTn I and T (cTnT are considered the “gold standard” for the non-invasive diagnosis of myocardial injury in human and animals. It has replaced traditionally used cardiac biomarkers such as myoglobin, lactate dehydrogenase (LDH, creatine kinase (CK and CK-MB due to its high sensitivity and specificity for the detection of myocardial injury. Cardiac troponins are proteins that control the calcium-mediated interaction between actin and myosin, allowing contraction at the sarcomere level. Concentration of the cTn can be correlated microscopic lesion and loss of immunolabeling in myocardium damage. Troponin concentration remains elevated in blood for 1-2wks so that wide window is available for diagnosis of myocardial damage. The cTn test has >95% specificity and sensitivity and test is less time consuming (10 to 15 minutes and less costly (INR 200 to INR 500. [Vet. World 2012; 5(8.000: 508-511

  13. Clinical perspective on C-reactive protein in prognostication of major adverse cardiac events in the elderly with established coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Olabode Oladeinde

    2006-01-01

    @@ The systemic response to tissue injury, regardless of cause is characterized by a cytokine-mediated alteration in the hepatic synthesis of a number of different plasma proteins,known collectively as 'acute phase reactants'. These proteins include C-reactive protein, serum amyloid A protein, alphal glycoprotein, ceruloplasmin, alpha macroglobulins, complement components (C1-C4, factor B, C9, C11), alpha1antitrypsin, alpha1 antichymotrypsin, fibrinogen, prothrombin,factor Ⅷ, plasminogen, haptoglobin, ferritin, immunoglobulins and lipoproteins. The initiation of the acute phase response is linked to the production of hormone-like polypeptide mediators now called cytokines, namedly, interleukin 1(IL-1),tumor necrosis factor, interferon gamma, interleukin 6 (IL-6),leukemia inhibitory factor, ciliary neurotropic factor, oncostatin M, and interleukin 11 (IL- 11).

  14. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    Science.gov (United States)

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2. PMID:24626813

  15. Alteration of cardiac progenitor cell potency in GRMD dogs.

    Science.gov (United States)

    Cassano, M; Berardi, E; Crippa, S; Toelen, J; Barthelemy, I; Micheletti, R; Chuah, M; Vandendriessche, T; Debyser, Z; Blot, S; Sampaolesi, M

    2012-01-01

    Among the animal models of Duchenne muscular dystrophy (DMD), the Golden Retriever muscular dystrophy (GRMD) dog is considered the best model in terms of size and pathological onset of the disease. As in human patients presenting with DMD or Becker muscular dystrophies (BMD), the GRMD is related to a spontaneous X-linked mutation of dystrophin and is characterized by myocardial lesions. In this respect, GRMD is a useful model to explore cardiac pathogenesis and for the development of therapeutic protocols. To investigate whether cardiac progenitor cells (CPCs) isolated from healthy and GRMD dogs may differentiate into myocardial cell types and to test the feasibility of cell therapy for cardiomyopathies in a preclinical model of DMD, CPCs were isolated from cardiac biopsies of healthy and GRMD dogs. Gene profile analysis revealed an active cardiac transcription network in both healthy and GRMD CPCs. However, GRMD CPCs showed impaired self-renewal and cardiac differentiation. Population doubling and telomerase analyses highlighted earlier senescence and proliferation impairment in progenitors isolated from GRMD cardiac biopsies. Immunofluorescence analysis revealed that only wt CPCs showed efficient although not terminal cardiac differentiation, consistent with the upregulation of cardiac-specific proteins and microRNAs. Thus, the pathological condition adversely influences the cardiomyogenic differentiation potential of cardiac progenitors. Using PiggyBac transposon technology we marked CPCs for nuclear dsRed expression, providing a stable nonviral gene marking method for in vivo tracing of CPCs. Xenotransplantation experiments in neonatal immunodeficient mice revealed a valuable contribution of CPCs to cardiomyogenesis with homing differences between wt and dystrophic progenitors. These results suggest that cardiac degeneration in dystrophinopathies may account for the progressive exhaustion of local cardiac progenitors and shed light on cardiac stemness in

  16. Blunt cardiac rupture.

    Science.gov (United States)

    Martin, T D; Flynn, T C; Rowlands, B J; Ward, R E; Fischer, R P

    1984-04-01

    Blunt injury to the heart ranges from contusion to disruption. This report comprises 14 patients seen during a 6-year period with cardiac rupture secondary to blunt trauma. Eight patients were injured in automobile accidents, two patients were injured in auto-pedestrian accidents, two were kicked in the chest by ungulates, and two sustained falls. Cardiac tamponade was suspected in ten patients. Five patients presented with prehospital cardiac arrest or arrested shortly after arrival. All underwent emergency department thoracotomy without survival. Two patients expired in the operating room during attempted cardiac repair; both had significant extracardiac injury. Seven patients survived, three had right atrial injuries, three had right ventricular injuries, and one had a left atrial injury. Cardiopulmonary bypass was not required for repair of the surviving patients. There were no significant complications from the cardiac repair. The history of significant force dispersed over a relatively small area of the precordium as in a kicking injury from an animal or steering wheel impact should alert the physician to possible cardiac rupture. Cardiac rupture should be considered in patients who present with signs of cardiac tamponade or persistent thoracic bleeding after blunt trauma. PMID:6708151

  17. Research progress of heart type fat binding protein and its application in cardiac surgery%心脏型脂肪结合蛋白的研究及在心脏外科的应用

    Institute of Scientific and Technical Information of China (English)

    王石雄; 李宁荫; 高秉仁

    2012-01-01

    背景:心脏型脂肪结合蛋白是心肌细胞胞浆中含量最丰富的蛋白质之一,是心肌损伤的标志蛋白.目的:归纳总结心脏型脂肪结合蛋白的生物学结构及功能、代谢动力学、临床研究进展及其在心脏外科的应用.方法:由第一作者检索1983-01/2010-12 PubMed数据及维普数据库与心脏型脂肪结合蛋白的生物学结构及功能有关的文献,心脏型脂肪结合蛋白在心脏外科中的应用及临床上应用相关文献.英文检索词为"heart fatty acid-binding protein,creatine kinaseisoenzyme,acute myocardial infarction,coronary artery bypass grafting";中文检索词为"心脏型脂肪结合蛋白,肌酸激酶同工酶,心肌梗死,冠状动脉旁路移植术".根据纳入标准保留62篇进行论述.结果与结论:心脏型脂肪结合蛋白是一种低分子量的可溶性蛋白,较特异的存在于心肌细胞质内;正常人的血浆中不含有或含有少量心脏型脂肪结合蛋白,在心肌受损后能快速释放.心脏型脂肪结合蛋白在体外循环冠状动脉搭桥后围手术期心肌损伤鉴别中具有良好的诊断价值;可以较早快速评价体外循环瓣膜置换术心肌损伤的潜在有用指标;脂肪酸结合蛋白的升高水平可较早的判断心肌损伤的程度,从而判断术后心功能受损的程度和与心脏有关的并发症.%BACKGROUND: Heart-type fatty-binding protein is one of the most abundant proteins in the cytoplasm of myocardial cells, which is a marker protein for myocardial injury. OBJECTIVE: To summarize the biology structure and function, metabolism dynamics of heart-type fatty binding protein, and their progress in clinical research and application in cardiac surgery. METHODS: A search of PubMed and VIP databases (1983-01/2010-12) was performed by the first author for the literature of the biological structure and function of heart-type fatty-binding proteins and their application in cardiac surgery as well as other

  18. 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 ...

  19. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  20. Perspectives on the value of biomarkers in acute cardiac care and implications for strategic management.

    Science.gov (United States)

    Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles

    2013-01-01

    Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management. PMID:24046510

  1. Large-scale characterization of the murine cardiac proteome.

    Science.gov (United States)

    Cosme, Jake; Emili, Andrew; Gramolini, Anthony O

    2013-01-01

    Cardiomyopathies are diseases of the heart that result in impaired cardiac muscle function. This dysfunction can progress to an inability to supply blood to the body. Cardiovascular diseases play a large role in overall global morbidity. Investigating the protein changes in the heart during disease can uncover pathophysiological mechanisms and potential therapeutic targets. Establishing a global protein expression "footprint" can facilitate more targeted studies of diseases of the heart.In the technical review presented here, we present methods to elucidate the heart's proteome through subfractionation of the cellular compartments to reduce sample complexity and improve detection of lower abundant proteins during multidimensional protein identification technology analysis. Analysis of the cytosolic, microsomal, and mitochondrial subproteomes separately in order to characterize the murine cardiac proteome is advantageous by simplifying complex cardiac protein mixtures. In combination with bioinformatic analysis and genome correlation, large-scale protein changes can be identified at the cellular compartment level in this animal model. PMID:23606244

  2. Low-carbohydrate/high-protein diet improves diastolic cardiac function and the metabolic syndrome in overweight-obese patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    H. von Bibra

    2014-03-01

    Conclusions: These data indicate, that a low-glycaemic/high-protein but not a low-fat/high-carbohydrate nutrition modulates diastolic dysfunction in overweight T2D patients, improves insulin resistance and may prevent or delay the onset of diabetic cardiomyopathy and the metabolic syndrome.

  3. [Cardiac evaluation before non-cardiac surgery].

    Science.gov (United States)

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  4. Cardiac calcium release channel (ryanodine receptor) in control and cardiomyopathic human hearts: mRNA and protein contents are differentially regulated.

    Science.gov (United States)

    Sainte Beuve, C; Allen, P D; Dambrin, G; Rannou, F; Marty, I; Trouvé, P; Bors, V; Pavie, A; Gandgjbakch, I; Charlemagne, D

    1997-04-01

    Abnormal intracellular calcium handling in cardiomyopathic human hearts has been associated with an impaired function of the sarcoplasmic reticulum, but previous reports on the gene expression of the ryanodine receptors (Ry2) are contradictory. We measured the mRNA levels, the protein levels and the number of high affinity [3H]ryanodine binding sites in the left ventricle of non-failing (n = 9) and failing human hearts [idiopathic dilated (IDCM n = 16), ischemic (ICM n = 7) or mixed (MCM n = 8) cardiomyopathies]. Ry2 mRNA levels were significantly reduced in IDCM (-30%) and unchanged in MCM and ICM and Ry2 protein levels were similar. In contrast, we observed a two-fold increase in the number of high affinity Ry2 (B(max) = 0.43 +/- 0.11 v 0.22 +/- 0.13 pmol/mg protein, respectively; P<0.01) and an unchanged K(d). Furthermore, levels of myosin heavy chain mRNA and protein per g of tissue were similar in failing and non-failing hearts, suggesting that the observed differences in Ry2 are not caused by the increase in fibrosis in failing heart. Therefore, the dissociation between the two-fold increase in the number of high affinity ryanodine receptors observed in all failing hearts and the slightly decreased mRNA level or unchanged protein level suggests that the ryanodine binding properties are affected in failing myocardium and that such modifications rather than a change in gene expression alter the channel activity and could contribute to abnormalities in intracellular Ca2+ handling. PMID:9160875

  5. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  6. [Cardiac Rehabilitation 2015].

    Science.gov (United States)

    Hoffmann, Andreas

    2015-11-25

    The goals of cardiac rehabilitation are (re-)conditioning and secondary prevention in patients with heart disease or an elevated cardiovascular risk profile. Rehabilitation is based on motivation through education, on adapted physical activity, instruction of relaxation techniques, psychological support and optimized medication. It is performed preferably in groups either in outpatient or inpatient settings. The Swiss working group on cardiac rehabilitation provides a network of institutions with regular quality auditing. Positive effects of rehabilitation programs on mortality and morbidity have been established by numerous studies. Although a majority of patients after cardiac surgery are being referred to rehabilitation, these services are notoriously underused after catheter procedures. PMID:26602848

  7. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed for...... uncertain and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  8. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    Science.gov (United States)

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. PMID:27056419

  9. Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

    OpenAIRE

    Shaon Naskar; Kaberi Datta; Arkadeep Mitra; Kanchan Pathak; Ritwik Datta; Trisha Bansal; Sagartirtha Sarkar

    2014-01-01

    A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week ...

  10. Molecular Basis of Cardiac Myxomas

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2014-01-01

    Full Text Available Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.

  11. Automatic Implantable Cardiac Defibrillator

    Medline Plus

    Full Text Available Automatic Implantable Cardiac Defibrillator February 19, 2009 Halifax Health Medical Center, Daytona Beach, FL Welcome to Halifax Health Daytona Beach, Florida. Over the next hour you' ...

  12. Sudden Cardiac Arrest

    Science.gov (United States)

    ... scan, or MUGA, which shows how well your heart is pumping blood. Magnetic resonance imaging (MRI) which gives doctors detailed pictures of your heart. How is SCA treated? Sudden cardiac arrest should ...

  13. Sudden Cardiac Arrest

    Science.gov (United States)

    ... Heart Risk Factors & Prevention Heart Diseases & Disorders Atrial Fibrillation (AFib) Sudden Cardiac Arrest (SCA) SCA: Who's At Risk? Prevention of SCA What Causes SCA? SCA Awareness Atrial Flutter Heart Block Heart Failure Sick Sinus Syndrome Substances & Heart Rhythm Disorders Symptoms & ...

  14. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Aranđelović Aleksandra Č.

    2004-01-01

    Full Text Available Sudden cardiac death in an athlete is rare and tragic event. An athlete's death draws high public attention given that athletes are considered the healthiest category of society. The vast majority of sudden cardiac death in young athletes is due to congenital cardiac malformations such as hypertrophie cardiomyopathy and various coronary artery anomalies. In athletes over age 35, the usual cause of sudden cardiac death is coronary artery disease. With each tragic death of a young athlete, there is a question why this tragedy has not been prevented. The American College of Sports Medicine and the American Heart Association recommend that a pre-participation exam should include a complete cardiovascular history and physical examination.

  15. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  16. The correlation between high sensitivity C-Reactive Protein level and the Extent of Coronary Lesion and Cardiac Systolic Function in Coronary Heart Disease

    OpenAIRE

    Miftah Suryadipradja; Sally A. Nasution; Dasnan Ismail; Yoga I. Kasjmir

    2003-01-01

    To determine the mean value of high sensitivity C-Reactive Protein (hs-CRP), association between plasma level of hs-CRP with extent of disease and systolic function. A cross sectional study had been conducted to 106 coronary artery disease patients (90 stable angina pectoris, 11 unstable angina pectoris and 5 acute myocardial infarction). Plasma quantitative level of hs-CRP with cor angiography to determine extent of disease and ejection fraction were measured. The mean of hs-CRP levels in pa...

  17. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  18. Safety in cardiac surgery

    OpenAIRE

    Siregar, S.

    2013-01-01

    The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for Cardio-Thoracic Surgery (NVT) database. The safety of care is usually measured using patient outcomes. If outcomes are not available, the process and structure of care may be used. Outcomes should be adjusted ...

  19. Cardiac rehabilitation in Germany.

    Science.gov (United States)

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  20. Ranolazine in Cardiac Arrhythmia.

    Science.gov (United States)

    Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C

    2016-03-01

    Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200

  1. Cardiac tumours in infancy

    OpenAIRE

    Yadava, O.P.

    2012-01-01

    Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspect...

  2. Cardiac Image Registration

    Directory of Open Access Journals (Sweden)

    2008-09-01

    Full Text Available Long procedure time and somewhat suboptimal results hinder the widespread use of catheter ablation of complex arrhythmias such as atrial fibrillation (AF. Due to lack of contrast differentiation between the area of interest and surrounding structures in a moving organ like heart, there is a lack of proper intraprocedural guidance using current imaging techniques for ablation. Cardiac image registration is currently under investigation and is in clinical use for AF ablation. Cardiac image registration, which involves integration of two images in the context of left atrium (LA, is intermodal, with the acquired image and the real-time reference image residing in different image spaces, and involves optimization, where one image space is transformed into the other. Unlike rigid body registration, cardiac image registration is unique and challenging due to cardiac motion during the cardiac cycle and due to respiration. This review addresses the basic principles of the emerging technique of registration and the inherent limitations as they relate to cardiac imaging and registration.

  3. Cardiac Image Registration

    Directory of Open Access Journals (Sweden)

    Jasbir Sra

    2008-09-01

    Full Text Available Long procedure time and somewhat suboptimal results hinder the widespread use of catheter ablation of complex arrhythmias such as atrial fibrillation (AF. Due to lack of contrast differentiation between the area of interest and surrounding structures in a moving organ like heart, there is a lack of proper intraprocedural guidance using current imaging techniques for ablation. Cardiac image registration is currently under investigation and is in clinical use for AF ablation. Cardiac image registration, which involves integration of two images in the context of the left atrium (LA, is intermodal, with the acquired image and the real-time reference image residing in different image spaces, and involves optimization, where one image space is transformed into the other. Unlike rigid body registration, cardiac image registration is unique and challenging due to cardiac motion during the cardiac cycle and due to respiration. This review addresses the basic principles of the emerging technique of registration and the inherent limitations as they relate to cardiac imaging and registration.

  4. Postoperative cardiac arrest due to cardiac surgery complications

    International Nuclear Information System (INIS)

    To examine the role of anesthetists in the management of cardiac arrest occurring in association with cardiac anesthesia. In this retrospective study we studied the potential performances for each of the relevant incidents among 712 patients undergoing cardiac operations at Golestan and Naft Hospitals Ahwaz between November 2006 and July 2008. Out of total 712 patients undergoing cardiac surgery, cardiac arrest occurred in 28 cases (3.9%) due to different postoperative complications. This included massive bleeding (50% of cardiac arrest cases, 1.9% of patients); pulseless supra ventricular tachycardia (28.5% of cardiac arrest cases, 1.1% of patients); Heart Failure (7% of cardiac arrest cases, 0.2% of patients); Aorta Arc Rapture (3.5% of cardiac arrest cases, 0.1% of patients); Tamponade due to pericardial effusion (3.5% of cardiac arrest cases, 0.1% of total patients); Right Atrium Rupture (3.5% of cardiac arrest cases, 0.1% of patients) were detected after cardiac surgery. Out of 28 cases 7 deaths occurred (25% of cardiac arrest cases, 0.1% of patients). The most prevalent reason for cardiac arrest during post operative phase was massive bleeding (50%) followed by pulseless supra ventricular tachycardia (28.5%). Six patients had some morbidity and the remaining 15 patients recovered. There are often multiple contributing factors to a cardiac arrest under cardiac anesthesia, as much a complete systematic assessment of the patient, equipment, and drugs should be completed. We also found that the diagnosis and management of cardiac arrest in association with cardiac anesthesia differs considerably from that encountered elsewhere. (author)

  5. Hypothyroidism and its rapid correction alter cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Georges Hajje

    Full Text Available The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10 group and a group treated with 6-propyl-2-thiouracil (PTU (n = 20 to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL6 and pro-fibrotic transforming growth factor beta 1 (TGF-β1, were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP and cardiac troponin T (cTnT were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  6. Biological determinants of aldosterone-induced cardiac fibrosis in rats.

    Science.gov (United States)

    Robert, V; Silvestre, J S; Charlemagne, D; Sabri, A; Trouvé, P; Wassef, M; Swynghedauw, B; Delcayre, C

    1995-12-01

    To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone. PMID:7490157

  7. Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    RONG Shu-ling; WANG Yong-jin; WANG Xiao-lin; LU Yong-xin; WU Yin; LIU Qi-yun; MI Shao-hua; XU Yu-lan

    2010-01-01

    Background Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.Methods Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n=6) and MI-GFP group (n=6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n=6)and S-GFP group (n=6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.Results Primary rat myoblasts were retrovirally transduced to

  8. Cardiac Hypertrophy: A Review on Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Ankur Rohilla

    2012-07-01

    Full Text Available Cardiac hypertrophy has been considered as an important risk factor for cardiac morbidity and mortality whose prevalence has increased during the last few decades. Cardiac hypertrophy, a disease associated with the myocardium, is characterized by thickening of ventricle wall of heart and consequent reduction in the contracting ability of heart to pump the blood. Cardiac hypertrophy has been divided into two types, i.e. physiological and pathological hypertrophy. The exercise-induced increase in the ability of pumping blood leads to thickening of ventricle wall, referred to as physiological hypertrophy. On the other hand, reduced ability of pumping blood as a result of hypertension and volume overload on heart denotes pathological hypertrophy. Numerous mediators have been found to be involved in the pathogenesis of cardiac hypertrophy that include mitogen-activated protein kinase (MAPK, protein kinase C (PKC insulin-like growth factor-I (IGF-I, phosphatidylinositol 3-kinase (PI3K-AKT/PKB, calcinurin-nuclear factor of activated T cells (NFAT and mammalian target of rapamycin (mTOR. The prevention strategy for cardiac hypertrophy involve thiazide diuretics, angiotensin-converting enzyme (ACE inhibitors, angiotensin (Ang II receptor blockers, beta blockers and calcium channel blockers. The present review article highlights the signaling mechanisms involved and the approaches required in the treatment of cardiac hypertrophy.

  9. DNA methylation in cardiac fibrosis: New advances and perspectives

    International Nuclear Information System (INIS)

    Cardiac fibrosis is characterized by net accumulation of extracellular matrix (ECM) proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. More specifically, cardiac fibroblasts are activated by a variety of pathological stimuli, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. Thus, understanding the biological processes of cardiac fibroblasts will provide novel insights into the underlying mechanisms of cardiac fibrosis. DNA methylation is an important epigenetic mechanism, which often occurs in response to environmental stimuli and is crucial in regulating gene expression. The aberrant methylation of CpG island promoters of selected genes is the prominent epigenetic mechanism by which gene transcription can be effectively silenced. Aberrant hypermethylation of a few selected genes such as RASSF1A plays an important role in facilitating fibrotic fibroblast activation and in driving fibrosis. In this review we will discuss the mechanisms of DNA methylation and their implications for cardiac fibroblasts activation and fibrosis. Control of DNA methylation may serve as a new strategy for anti-fibrotic therapy

  10. The role of protein kinase C in the transition from cardiac hypertrophy to failure induced by ascending aortic banding in rats

    International Nuclear Information System (INIS)

    Objective: To evaluate protein kinase C (PKC) activity and its contribution in the transition from pressure overload hypertrophy (POH) to congestive heart failure (CHF). Methods: Rat model of pressure overload heart failure was induced by ascending aorta banding of young Wistar rats. PKC activity was determined by measuring the incorporation of 32P from γ-32P-ATP into protamine. Results: Compared with sham-operated groups, in the CHF group, 12 weeks after operation, heart weight (HW) and HW/body weight (BW) increased 71.3% and 69.5%, respectively, with normal +- dp/dtmax (P>0.05); 20 weeks later, HW and HW/BW were 80% and 94% higher, respectively (Pmat (P0.05), but the M/C increased (P<0.01). Conclusions: The activity of PKC was constantly activated in these two pathological stages. PKC was activated in an escalating manner in POH. These data indicate that PKC might play a key regulatory role in the development of pressure overload heart failure

  11. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

    OpenAIRE

    Harris, Brett S.; Zhang, Yuhua; Card, Lauren; Rivera, Lee B.; Brekken, Rolf A.; Bradshaw, Amy D.

    2011-01-01

    Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associa...

  12. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  13. Early glycogen synthase kinase-3β and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.

    Science.gov (United States)

    Majd, Shohreh; Power, John H T; Koblar, Simon A; Grantham, Hugh J M

    2016-08-01

    Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation. PMID:27177932

  14. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery.

    Science.gov (United States)

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M; Lorente, Juan; Cerón, José J; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determine systemic inflammation and myocardial damage. This study was conducted on 33 dogs with BAOS that were evaluated before and 1 to 2 mo after surgical correction. Palatoplasty was carried out by means of 2 different surgical techniques: carbon dioxide (CO2) laser (n = 12) and electrical scalpel (n = 21). Biomarker levels (CRP, Hp, and cTnI) were determined before and after surgery. There was a significant reduction in respiratory and gastrointestinal signs in dogs with BAOS after surgical treatment (P < 0.001). A greater reduction in respiratory signs (P < 0.002) was obtained using the CO2 laser. No statistical differences were found between CRP and cTnI levels, either before or after surgical correction. Haptoglobin concentration did increase significantly in the postsurgical period (P < 0.008). Surgical treatment in dogs with BAOS reduces clinical signs, regardless of the anatomical components present. Surgical treatment for BAOS is not useful to reduce CRP and Hp levels, probably because BAOS does not induce as obvious an inflammatory process in dogs as in human patients with OSAS. No reduction in cTnI levels was observed 1 mo after surgery in dogs with BAOS, which suggests that some degree of myocardial damage remains. PMID:25673910

  15. Giant Cardiac Cavernous Hemangioma.

    Science.gov (United States)

    Unger, Eric; Costic, Joseph; Laub, Glenn

    2015-07-01

    We report the case of an asymptomatic giant cardiac cavernous hemangioma in a 71-year-old man. The intracardiac mass was discovered incidentally during surveillance for his prostate cancer; however, the patient initially declined intervention. On presentation to our institution 7 years later, the lesion had enlarged significantly, and the patient consented to excision. At surgery, an 8 × 6.5 × 4.8 cm intracardiac mass located on the inferior heart border was excised with an intact capsule through a median sternotomy approach. The patient had an uneventful postoperative course. We discuss the diagnostic workup, treatment, and characteristics of this rare cardiac tumor. PMID:26140782

  16. Radiography in cardiology [cardiac disorders, cardiac insufficiency

    International Nuclear Information System (INIS)

    The diagnostic procedure in cardiology nearly always requires an X-ray examination of the thorax. This examination is very informative when it is correctly performed and interpreted. The radiographs need to be read precisely and comprehensively: this includes the evaluation of the silhouette of the heart (size, form and position) as well as the examination of extra-cardiac thoracic structures allowing among other things to search for signs of cardiac insufficiency. The conclusion of the X-ray examination can be drawn after having brought together information concerning the case history, the clinical examination and the study of the radiographs. The radiologist finds himself in one of three situations: (1) the information provided by the X-ray pictures is characteristic of a disease and permits a diagnosis, (2) the X-ray pictures indicate a group of hypotheses; further complementary tests could be useful and (3) the X-ray pictures provide ambiguous even contradictory information; it is necessary to complete the radiological examination by other techniques such as an ultrasonographic study of the heart

  17. Serum myoglobin after cardiac catheterisation.

    OpenAIRE

    McComb, J. M.; McMaster, E A

    1982-01-01

    Study of 80 consecutive patients undergoing elective diagnostic cardiac catheterisation showed that after the procedure 25 (31%) developed myoglobinaemia. This was attributed to complications of the catheterisation in two. The remaining 23 had received premedication by intramuscular injection. In patients without intramuscular injections myoglobinaemia did not occur after uncomplicated cardiac catheterisation. The study did not support the proposition that cardiac catheterisation results in m...

  18. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-α-mediated transcription of fatty acid metabolic genes

    International Nuclear Information System (INIS)

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-α plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-α activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-α mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-α-mediated FA metabolic gene transcription

  19. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  20. Primary cardiac tumors

    International Nuclear Information System (INIS)

    Cardiac tumors happen to be among the less known pathologies without clear treatment standards. Even one decade ago most of the cardiac tumor diagnosis were made post mortem, and only reports of isolated cases could be found in the literature, showing the lack of interest in the investigation of these pathologies by cardiology and cardiovascular surgery specialists. With the development of echocardiography and of cardiovascular surgery, more cases of primary and metastatic cardiac tumors have been diagnosed. Many cases have been treated by palliative or curative surgical interventions, thus increasing the reports in the world literature and the experience in this field, and pointing out the real incidence of these pathologies, not being as bizarre as it had been considered. a revision of the literature will be made, in which the frequency and the suggested interventions will be reported, as well as the cases of cardiac pathology in two cardiovascular centers of the country known by the author. The echocardiographic, pathologic and histological characteristics of the representative cases will be presented, without a greater evidence level, due to the problem's incidence and the few cases reported by these centers

  1. Cardiac MRI tagging

    International Nuclear Information System (INIS)

    Cardiac MRI tagging is an original technique based upon the perturbation of the magnetization of determined regions of the myocardium (tags). The motion of the tags accurately reflects the deformation of the underlying tissue. Data analysis requires special techniques to reconstruct the 3D motion of the heart, and to evaluate the myocardial strain, locally and throughout the whole heart. (authors)

  2. Automatic Implantable Cardiac Defibrillator

    Medline Plus

    Full Text Available ... Over the next hour you'll see the implantation of an automated implantable cardiac defibrillator. The surgery ... evening we're going to be discussing the implantation of a defibrillator. It’s a battery-powered implantable ...

  3. Cardiac effects of vasopressin.

    Science.gov (United States)

    Pelletier, Jean-Sébastien; Dicken, Bryan; Bigam, David; Cheung, Po-Yin

    2014-07-01

    Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits. PMID:24621650

  4. Cardiac pacemaker power sources

    International Nuclear Information System (INIS)

    A review of chemical and radioisotope batteries used in cardiac pacemakers is presented. The battery systems are examined in terms of longevity, reliability, cost, size and shape, energy density, weight, internal resistance versus time, end-of-life voltage, chemical compatibility, and potential failure mechanisms

  5. Signaling Pathways Involved in Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Tao Zewei; Li Longgui

    2006-01-01

    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  6. [Cardiac amyloidosis. General review].

    Science.gov (United States)

    Laraki, R

    1994-04-01

    Cardiac amyloidosis, most often of AL type, is a non-exceptional disease as it represents 5 to 10% of non-ischemic cardiomyopathies. It realizes typically a restrictive cardiomyopathy. Nevertheless the wide diversity of possible presentation makes it a "big shammer" which must be evoked in front of every unexplained cardiopathy after the age of forty. If some associated manifestations can rapidly suggest the diagnosis, as a peripheric neuropathy especially a carpal tunnel syndrome or palpebral ecchymosis, cardiac involvement can also evolve in an apparently isolated way. The most suggestive paraclinic elements for the diagnosis are, in one hand, the increased myocardial echogenicity with a "granular sparkling" appearance seen throughout all walls of the left ventricle and, in the other hand, the association of a thickened left ventricle and a low voltage (electrocardiogram could also show pseudo-infarct Q waves). In front of such aspects, the proof of amyloidosis is brought by an extra-cardiac biopsy or by scintigraphy with labelled serum amyloid P component, so that the indications of endomyocardial biopsy are very limited today. The identification of the amyloid nature of a cardiopathy has an direct therapeutic implication: it contra-indicates the use of digitalis, calcium channel blockers and beta-blockers. The treatment of AL amyloidosis (chemotherapy with alkylant agents) remains very unsatisfactory especially in the cardiac involvement which is the most frequent cause of death (in AL amyloidosis). Last, cardiac amyloidosis is a bad indication for transplantation which results are burden by rapid progression of deposits especially in the gastro-intestinal tract and the nervous system. PMID:8059146

  7. Cardiac surgery outcomes.

    Science.gov (United States)

    Halpin, Linda S; Barnett, Scott D; Beachy, Jim

    2003-01-01

    Accrediting organizations and payers are demanding valid and reliable data that demonstrate the value of services. Federal agencies, healthcare industry groups, and healthcare watchdog groups are increasing the demand for public access to outcomes data. A new and growing outcomes dynamic is the information requested by prospective patients in an increasingly consumer-oriented business. Patients demand outcomes, and resources are developing to meet these demands. Physicians are increasingly confronted with requests for information about their mortality and morbidity rates, malpractice suits, and disciplinary actions received. For example, in Virginia, prospective patients have access to data provided by the nonprofit group Virginia Health Information. After numerous resolutions by the Virginia Senate since 1999, the prospective Virginia medical consumer now has access to several annual publications: Virginia Hospitals: A Consumer's Guide, 1999 Annual Report and Strategic Plan Update, and the 1999 Industry Report: Virginia Hospitals and Nursing Facilities. Consumers have access to cardiac outcomes data stratified by hospital, gender, and cardiac service line (cardiac surgery, noninvasive cardiology, and invasive cardiology). This is particularly relevant to IHI because Virginia Health Information specifically targets cardiac care. IHI has a sizable investment in cardiovascular outcomes and has found outcomes measurement and research are key to providing quality care. IHI's goal is to move from an outcomes management model to a disease management model. The hope is to incorporate all aspects of the patient's continuum of care, from preoperative and diagnostic services through cardiac interventions to postoperative rehabilitation. Furthermore, every step along the way will be supported with functional status and quality of life assessments. Although these goals are ambitious and expensive, the return on investment is high. PMID:14618772

  8. Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Da-Long Wu; Hui-Xing Yi; Feng-Ying Sui; Xiao-Hong Jiang; Xiao-Ming Jiang; Ying-Ying Zhao

    2006-01-01

    AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its clinicopathologic significance, in comparison with distal gastric adenocarcinomas.METHODS: Immunohistochemical avidin-biotin peroxidase complex method was applied to detect the expression of ATP7B in 49 cases of cardiac carcinomas,the corresponding adjacent non-neoplastic epithelium and 55 cases of distal gastric carcinomas.RESULTS: The proportion of ATP7B positive samples in gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49)(P = 0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was significantly higher than that in well/moderately differentiated gastric cardiac carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was independent of age, tumor size, nodal stage and metastasis status. ATP7B protein was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower than that in gastric cardiac carcinomas (P = 0.037).CONCLUSION: ATP7B protein is frequently overexpressed in gastric cardiac carcinomas, and correlated with the differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac carcinomas is significantly higher than that in distal gastric carcinomas, which might partially explain the difference of chemotherapy response and prognosis between these two gastric carcinomas.

  9. Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT

    DEFF Research Database (Denmark)

    Perkiomaki, Juha S; Ruwald, Anne-Christine; Kutyifa, Valentina;

    2015-01-01

    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...

  10. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

    2014-09-15

    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  11. Increased oxidative DNA damage, inducible nitric oxide synthase,nuclear factor κB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Chi-Sen Chang; Wei-Na Chen; Hui-Hsuan Lin; Cheng-Chung Wu; Chau-Jong Wang

    2004-01-01

    AIM: Several epidemiological studies have demonstrated a close association between Helicobacter pylori (H Pylori)infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of Hpyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due to oxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cell leukemia-1 (Mcl-1)] by Western-blot assay.RESULTS: The concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were detected in patients infected with H pylori compared with patients who were not infected with H pylori. Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients.CONCLUSION: Chronic H pylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the hypothesis that oxygen

  12. Expression of sterol regulatory element-binding transcription factor (SREBF 2 and SREBF cleavage-activating protein (SCAP in human atheroma and the association of their allelic variants with sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Kytömäki Leena

    2008-12-01

    Full Text Available Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2 and the SREBF cleavage-activating protein (SCAP. We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314 and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD. Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02 down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V, but not in the aorta or femoral arteries (p = NS for both, as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046. Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71, compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the

  13. Pathophysiology and treatment of cardiac amyloidosis.

    Science.gov (United States)

    Gertz, Morie A; Dispenzieri, Angela; Sher, Taimur

    2015-02-01

    Amyloid cardiomyopathy should be suspected in any patient who presents with heart failure and preserved ejection fraction. In patients with echocardiographic evidence of ventricular thickening and without a clear history of hypertension, infiltrative cardiomyopathy should be considered. If imaging suggests the presence of amyloid deposits, confirmation by biopsy is required, although endomyocardial biopsy is generally not necessary. Assessment of aspirated subcutaneous fat and bone-marrow biopsy samples verifies the diagnosis in 40-80% of patients, dependent on the type of amyloidosis. Mass spectroscopy can be used to determine the protein subunit and classify the disease as immunoglobulin light-chain amyloidosis or transthyretin-related amyloidosis associated with mutant or wild-type TTR (formerly known as familial amyloid cardiomyopathy and senile cardiac amyloidosis, respectively). In this Review, we discuss the characteristics of cardiac amyloidosis, and present a structured approach to both the assessment of patients and treatment with emerging therapies and organ transplantation. PMID:25311231

  14. Cardiac arrest in children

    Directory of Open Access Journals (Sweden)

    Tress Erika

    2010-01-01

    Full Text Available Major advances in the field of pediatric cardiac arrest (CA were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners.

  15. Cardiac arrest in children.

    Science.gov (United States)

    Tress, Erika E; Kochanek, Patrick M; Saladino, Richard A; Manole, Mioara D

    2010-07-01

    Major advances in the field of pediatric cardiac arrest (CA) were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners. PMID:20930971

  16. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    recruitment and participation among low educated and socially vulnerable patients must be addressed to lower inequality in post-MI health. Our aim was to improve referral, attendance, and adherence rates among socially vulnerable patients by systematic screening and by offering a socially differentiated...... standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social...

  17. Cardiac metastases of osteosarcoma

    International Nuclear Information System (INIS)

    Osteosarcoma is a malignancy whose various sites of metastasis greatly modify its ultimate prognosis. We report a case of simultaneous pulmonary and cardiac metastases in a 41-year-old male patient with osteosarcoma of the tibia, presenting after more then one year of completion of adjuvant therapy with progressive dyspnea and cyanosis. Diagnosis was made on computerized tomogram and echocardiogram. The metastatic mass entirely occupying the right ventricle and the pulmonary artery proved fatal. (author)

  18. Cardiac Tissue Engineering

    OpenAIRE

    MILICA RADISIC; GORDANA VUNJAK-NOVAKOVIC

    2009-01-01

    We hypothesized that clinically sized (1-5 mm thick),compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3) can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of p...

  19. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  20. Penetrating Cardiac Injuries

    OpenAIRE

    ÖZYAZICIOĞLU, Ahmet

    2002-01-01

    Objectives: To present our experience of penetrating cardiac injuries treated at Atatürk University hospital; in 17 years 38 patients were analyzed. Methods: Patients were classified into three groups: group A (stable), 12; group B (shock), 21; and group C (agonal), five. Five patients were treated by pericardial window and three by pericardiocentesis. Two patients in group C, 19 patients in group B and five patients in group A underwent median sternotomy or thoracotomy in the operating room...

  1. Benign cardiac tumours: cardiac CT and MRI imaging appearances

    International Nuclear Information System (INIS)

    Full text: Primary benign cardiac tumours are rarely found in clinical practice and are generally evaluated with echocardiography. However, with the increasing usage of helical multislice CT, the initial detection and evaluation of these masses may be made by the radiologist during routine daily practice for other indications. The echocardiographic, CT and cardiac MRI appearances of various benign cardiac tumours and masses are described and illustrated in this review

  2. Calcium Sensing Receptor Promotes Cardiac Fibroblast Proliferation and Extracellular Matrix Secretion

    Directory of Open Access Journals (Sweden)

    Xinying Zhang

    2014-02-01

    Full Text Available Aims: Calcium-sensing receptor (CaR acts as a G protein coupled receptor that mediates the increase of the intracellular Ca2+ concentration. The expression of CaR has been confirmed in various cell types, including cardiomyocytes, smooth muscle cells, neurons and vascular endothelial cells. However, whether CaR is expressed and functions in cardiac fibroblasts has remained unknown. The present study investigated whether CaR played a role in cardiac fibroblast proliferation and extracellular matrix (ECM secretion, both in cultured rat neonatal cardiac fibroblasts and in a model of cardiac hypertrophy induced by isoproterenol (ISO. Methods and Results: Immunofluorescence, immunohistochemistry and Western blot analysis revealed the presence of CaR in cardiac fibroblasts. Calcium and calindol, a specific activator of CaR, elevated the intracellular calcium concentration in cardiac fibroblasts. Pretreatment of cardiac fibroblasts with calhex231, a specific inhibitor of CaR, U73122 and 2-APB attenuated the calindol- and extracellular calcium-induced increase in intracellular calcium ([Ca2+]i. Cardiac fibroblast proliferation and migration were assessed by MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, cell count and the cell scratch assay. ECM production was detected by expression of matrix metalloproteinase-3 and -9 (MMP-3 and -9. Activation of CaR promoted cardiac fibroblast proliferation and migration and ECM secretion. More importantly, calhex231, suppressed cardiac fibroblast proliferation and migration and MMP-3 and -9 expression. To further investigate the effect of CaR on cardiac fibrosis, a model of ISO-induced cardiac hypertrophy was established. Pretreatment with calhex231 prevented cardiac fibrosis and decreased the expression of MMP-3 and -9 expression. Conclusions: Our results are the first report that CaR plays an important role in Ca2+ signaling involved in cardiac fibrosis through the phospholipase C- inositol 3

  3. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  4. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  5. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac p...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....... characterized. An ongoing characterization of the molecular heterogeneity will help appreciate the biosynthetic capacity of the endocrine heart and could introduce new diagnostic possibilities. Notably, different biosynthetic products may not be equal markers of the same pathophysiological processes. An...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  6. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....

  7. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  8. Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Valerie Joers

    Full Text Available Cardiac sympathetic neurodegeneration and dysautonomia affect patients with sporadic and familial Parkinson's disease (PD and are currently proposed as prodromal signs of PD. We have recently developed a nonhuman primate model of cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA. Our in vivo findings included decreased cardiac uptake of a sympathetic radioligand and circulating catecholamines; here we report the postmortem characterization of the model. Ten adult rhesus monkeys (5-17 yrs old were used in this study. Five animals received 6-OHDA (50 mg/kg i.v. and five were age-matched controls. Three months post-neurotoxin the animals were euthanized; hearts and adrenal glands were processed for immunohistochemistry. Quantification of immunoreactivity (ir of stainings was performed by an investigator blind to the treatment group using NIH ImageJ software (for cardiac bundles and adrenals, area above threshold and optical density and MBF StereoInvestigator (for cardiac fibers, area fraction fractionator probe. Sympathetic cardiac nerve bundle analysis and fiber area density showed a significant reduction in global cardiac tyrosine hydroxylase-ir (TH; catecholaminergic marker in 6-OHDA animals compared to controls. Quantification of protein gene protein 9.5 (pan-neuronal marker positive cardiac fibers showed a significant deficit in 6-OHDA monkeys compared to controls and correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte antigen-ir (inflammatory marker and nitrotyrosine-ir (oxidative stress marker did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle α-synuclein-ir (presynaptic protein was reduced (trend in 6-OHDA treated monkeys; insoluble proteinase-K resistant α-synuclein (typical of PD pathology was not observed. In the adrenal medulla, 6-OHDA monkeys had significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm that systemic 6-OHDA dosing to nonhuman primates

  9. Sudden Cardiac Death in Athletes.

    Science.gov (United States)

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  10. Cardiac Rehabilitation: Guidelines and Recommendations

    OpenAIRE

    Catherine Monpere

    1998-01-01

    Cardiac rehabilitation has been shown to improve exercise tolerance and symptomatology in patients experiencing angina or heart failure and reduce long term mortality after myocardial infarction, with a good cost-effectiveness ratio. In addition to these `hard' endpoints, cardiac rehabilitation improves the patient's quality of life and risk factor profile through a multifactorial intervention. Indeed, cardiac rehabilitation is no longer restricted to physical reconditioning, but should now b...

  11. Diagnostic imaging of cardiac hypertrophy

    International Nuclear Information System (INIS)

    As imaging techniques for cardiac hypertrophy, the ultrasonic dimension gauze technique, echocardiography, ventriculography and the RI technique including emission RI tomography were outlined. (Chiba, N.)

  12. Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos.

    Science.gov (United States)

    Duan, Junchao; Yu, Yang; Li, Yang; Li, Yanbo; Liu, Hongcui; Jing, Li; Yang, Man; Wang, Ji; Li, Chunqi; Sun, Zhiwei

    2016-06-01

    The toxicity mechanism of nanoparticles on vertebrate cardiovascular system is still unclear, especially on the low-level exposure. This study was to explore the toxic effect and mechanisms of low-dose exposure of silica nanoparticles (SiNPs) on cardiac function in zebrafish embryos via the intravenous microinjection. The dosage of SiNPs was based on the no observed adverse effect level (NOAEL) of malformation assessment in zebrafish embryos. The mainly cardiac toxicity phenotypes induced by SiNPs were pericardial edema and bradycardia but had no effect on atrioventricular block. Using o-Dianisidine for erythrocyte staining, the cardiac output of zebrafish embryos was decreased in a dose-dependent manner. Microarray analysis and bioinformatics analysis were performed to screen the differential expression genes and possible pathway involved in cardiac function. SiNPs induced whole-embryo oxidative stress and neutrophil-mediated cardiac inflammation in Tg(mpo:GFP) zebrafish. Inflammatory cells were observed in atrium of SiNPs-treated zebrafish heart by histopathological examination. In addition, the expression of TNNT2 protein, a cardiac contraction marker in heart tissue had been down-regulated compared to control group using immunohistochemistry. Confirmed by qRT-PCR and western blot assays, results showed that SiNPs inhibited the calcium signaling pathway and cardiac muscle contraction via the down-regulated of related genes, such as ATPase-related genes (atp2a1l, atp1b2b, atp1a3b), calcium channel-related genes (cacna1ab, cacna1da) and the regulatory gene tnnc1a for cardiac troponin C. Moreover, the protein level of TNNT2 was decreased in a dose-dependent manner. For the first time, our results demonstrated that SiNPs induced cardiac dysfunction via the neutrophil-mediated cardiac inflammation and cardiac contraction in zebrafish embryos. PMID:26551753

  13. Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.

    Directory of Open Access Journals (Sweden)

    Elisa Belian

    Full Text Available Adult cardiac stem cells (CSCs express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd-a co-activator not only for serum response factor, but also for Gata4 and Tbx5-is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT, and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains. MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized.(1 GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2 Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3 Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

  14. Cardiac voltage-gated calcium channel macromolecular complexes.

    Science.gov (United States)

    Rougier, Jean-Sébastien; Abriel, Hugues

    2016-07-01

    Over the past 20years, a new field of research, called channelopathies, investigating diseases caused by ion channel dysfunction has emerged. Cardiac ion channels play an essential role in the generation of the cardiac action potential. Investigators have largely determined the physiological roles of different cardiac ion channels, but little is known about the molecular determinants of their regulation. The voltage-gated calcium channel Cav1.2 shapes the plateau phase of the cardiac action potential and allows the influx of calcium leading to cardiomyocyte contraction. Studies suggest that the regulation of Cav1.2 channels is not uniform in working cardiomyocytes. The notion of micro-domains containing Cav1.2 channels and different calcium channel interacting proteins, called macro-molecular complex, has been proposed to explain these observations. The objective of this review is to summarize the currently known information on the Cav1.2 macromolecular complexes in the cardiac cell and discuss their implication in cardiac function and disorder. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26707467

  15. Cardiac manifestations of myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Petri, Helle; Vissing, John; Witting, Nanna; Bundgaard, Henning; Køber, Lars

    2012-01-01

    To estimate the degree of cardiac involvement regarding left ventricular ejection fraction, conduction abnormalities, arrhythmia, risk of sudden cardiac death (SCD) and the associations between cardiac involvement and cytosine-thymine-guanine (CTG)-repeat, neuromuscular involvement, age and gender...

  16. Optimized method for identification of the proteomes secreted by cardiac cells

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Van Eyk, J.E.

    2013-01-01

    Roč. 1005, č. 1005 (2013), s. 225-235. ISSN 1940-6029 Institutional support : RVO:68081715 Keywords : cardiac cells * secreted proteins * proteomic technology Subject RIV: CB - Analytical Chemistry, Separation

  17. Antifibrinolytics in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Achal Dhir

    2013-01-01

    Full Text Available Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA or epsilon amino caproic acid (EACA. While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

  18. Unique type of isolated cardiac valvular amyloidosis

    Directory of Open Access Journals (Sweden)

    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  19. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  20. Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation.

    Science.gov (United States)

    Chan, Elsa C; Dusting, Gregory J; Guo, Nancy; Peshavariya, Hitesh M; Taylor, Caroline J; Dilley, Rodney; Narumiya, Shuh; Jiang, Fan

    2010-08-01

    Cardiac fibrosis is a consequence of many cardiovascular diseases and contributes to impaired ventricular function. Activation of the prostacyclin receptor (IP) protects against cardiac fibrosis, but the molecular mechanisms are not totally understood. Using mouse cardiac fibroblasts, we found that IP activation with cicaprost suppressed expression of collagen I and other target genes of transforming growth factor-beta. This effect of cicaprost was unlikely to be mediated by inhibition of the Smad2/3 or mitogen-activated protein kinase (MAPK) activities, but was associated with cAMP elevation and phosphorylation of the transcription factor cAMP response element binding protein (CREB). Expression of a non-phosphorylated CREB mutant suppressed the inhibitory effect of cicaprost. It appears that phosphorylated CREB binds to and sequestrates the transcription coactivator CBP/p300 from binding to Smad. Inhibition of the intrinsic histone acetyl-transferase activity of CBP/p300 with garcinol significantly suppressed collagen I expression in fibroblasts. Using apolipoprotein E and IP double knockout mouse, we demonstrated that endogenous prostacyclin/IP signaling had an inhibitory effect on angiotensin II-induced cardiac fibrosis under hypercholesterolemic conditions. Taken together, our results suggest that the prostacyclin/IP pathway suppresses cardiac fibrosis, at least partly, by inducing CREB phosphorylation. PMID:20403362

  1. The change and significance of heart fatty acid-binding protein and cardiac troponin Ⅰ in valve replacement patients%心脏瓣膜置换围手术期H-FABP和cTnI的变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈志军; 王永连; 王忠民

    2011-01-01

    目的 探讨心脏瓣膜置换术后心肌肌钙蛋白I(cTnI)和心型脂肪酸结合蛋白(H-FABP)的变化规律.方法 选本院风湿性心脏病手术患者40例,随机分为晶体停搏液灌注组和冷血停搏液灌注组,选取8个时间点,分析和比较各时点血清cTnI和H-FABP浓度变化规律.结果 晶体停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=2744.397,P<0.01; F交互=125.345,P<0.01),冷血停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=1056.357,P<0.01; F交互 =64.242,P<0.01);晶体停搏液灌注组H- FABP组间及交互效应差异均有统计学意义(F组间=1775.022,P<0.01;F交互=34.297,P<0.01),冷血停搏液灌注组H -FABP组间及交互效应差异均有统计学意义(F组间=3064.451,P<0.01;F交互=60.472,P<0.01).结论 H-FABP心肌的特异性强,有效诊断窗口期短,较符合心肌损伤的理想判定标志物.%Objective To explore change trend of Cardiac Troponin Ⅰ (cTnI) and Heart Fatty Acid-binding Protein(H-FABP) in serum during the perioperation of valve replacement.Methods Forty patients with heumatoid valvular heart disease were selected for this study,and the patients were randomly divided into two groups.Blood samples were taken from center vein,and the serum levels of cTnI and H-FABP were determined.The change of the serum levels of these two markers at different time points was recorded and compared between two groups.Results There were significant differences in the concentration of cTnl in the cold crystalloid cardioplegia group ( F between group =2744.397,P <0.01 ; F interaction =125.345,P <0.01 ).There were significant differences in the concentration of cTnI in the cold blood cardioplegia group ( F between group =1056.357,P < 0.01 ; Finteraction =64.242,P < 0.01 ).There were significant differences in the concentration of H - FABP in the cold crystalloid cardioplegia group ( F between group =1775.022,P <0.01; F

  2. Tenascin C upregulates IL-6 expression in Human Cardiac Myofibroblasts via Toll-Like Receptor 4

    OpenAIRE

    Midwood, KS; Maqbool, A; Spary, EJ; Manfield, IW; Ruhmann, M; Zuliani-Alvarez, L; Gamboa-Esteves, FO; Porter, KE; Drinkhill, MJ; Turner, NA

    2016-01-01

    AIM: To investigate the effect of Tenascin-C (TNC) on the expression of pro-inflammatory cytokines and matrix metalloproteinases in human cardiac myofibroblasts. METHODS: Cardiac myofibroblasts (CMF) were isolated and cultured from patients undergoing coronary artery bypass grafting. Cultured cells were treated with either TNC (0.1 µM, 24 h) or a recombinant protein corresponding to different domains of the TNC protein; fibrinogen-like globe (FBG) and fibronectin type III-like repeats (TN...

  3. Hypokalemia and sudden cardiac death

    DEFF Research Database (Denmark)

    Kjeldsen, Keld

    2010-01-01

    Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient...... of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis....

  4. Atrial tumors in cardiac MRI

    International Nuclear Information System (INIS)

    Cardiac magnetic resonance imaging (MRI) is an important tool for the diagnosis of cardiac masses. Various cardiac tumors are predisposed to occurring in atrial structures. The aim of this review article is the description of atrial tumors and their morphological features in MRI. In general, cardiac tumors are rare: approximately 0.001-0.03% in autopsy studies. About 75% of them are benign. The most common cardiac tumor is the myxoma. They are predisposed to occur in the atria and show a characteristically strong hyperintense signal on T2-wieghted images in MRI. In other sequences a heterogeneous pattern reflects its variable histological appearance. Lipomas exhibit a signal behavior identical to fatty tissue with a typical passive movement in cine imaging. Fibroelastomas are the most common tumors of the cardiac valves. Consisting of avascular fibrous tissue, they often present with hypointense signal intensities. Thrombi attached to their surface can cause severe emboli even in small tumors. Amongst primary cardiac malignancies, sarcomas are most common and favor the atria. Secondary malignancies of the heart are far more common than primary ones (20-40 times). In case of known malignancies, approximately 10% of patients develop cardiac metastasis at the end of their disease. Lymphogenic metastases favor the pericardium, while hematogenic spread prefers the myocardium. Since they are not real atrial tumors, thrombi and anatomical structures of the atria have to be differentiated from other pathologies. (orig.)

  5. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  6. Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall.

    Science.gov (United States)

    Wang, Ting; Miller, Kenneth E

    2016-08-01

    The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside ICG. In the present study, rat ICG neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac

  7. Pneumothorax in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;

    2012-01-01

    AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort.METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish...... patients who received their first pacemaker (PM) or cardiac resynchronization device from 1997 to 2008. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the association between risk factors and pneumothorax treated with a chest tube. The median...... age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary...

  8. Leadership in cardiac surgery.

    Science.gov (United States)

    Rao, Christopher; Patel, Vanash; Ibrahim, Michael; Ahmed, Kamran; Wong, Kathie A; Darzi, Ara; von Segesser, Ludwig K; Athanasiou, Thanos

    2011-06-01

    Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance. PMID:20884217

  9. Cardiac chamber scintiscanning

    International Nuclear Information System (INIS)

    The two methods of cardiac chamber scintiscanning, i.e. 'first pass' and 'ECG-triggered' examinations, are explained and compared. Two tables indicate the most significant radiation doses of the applied radio tracers, i.e. 99m-Tc-pertechnetate and 99m-Tc-HSA, to which a patient is exposed. These averaged values are calculated from various data given in specialised literature. On the basis of data given in literature, an effective half-life of approximately 5 hours in the intravascular space was calculated for the erythrocytes labelled with technetium 99m. On this basis, the radiation doses for the patients due to 99m-Tc-labelled erythrocytes are estimated. The advantages and disadvantages of the two methods applied for cardiac chamber scintiscanning are put into contrast and compared with the advantages and disadvantages of the quantitative X-ray cardiography of the left heart. The still existing problems connected with the assessment of ECG-triggered images are discussed in detail. The author performed investigations of his own, which concerned the above-mentioned problems. (orig./MG)

  10. Affect intensity and cardiac arousal.

    Science.gov (United States)

    Blascovich, J; Brennan, K; Tomaka, J; Kelsey, R M; Hughes, P; Coad, M L; Adlin, R

    1992-07-01

    Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990). PMID:1494983

  11. Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts

    Directory of Open Access Journals (Sweden)

    McLarty JL

    2013-08-01

    Full Text Available Jennifer L McLarty,1 Jianping Li,2 Scott P Levick,3 Joseph S Janicki2 1Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC, USA; 3Department of Pharmacology and Toxicology, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA Background: Inflammatory cells play a major role in the pathology of heart failure by stimulating cardiac fibroblasts to regulate the extracellular matrix in an adverse way. In view of the fact that inflammatory cells have estrogen receptors, we hypothesized that estrogen provides cardioprotection by decreasing the ability of cardiac inflammatory cells to influence fibroblast function. Methods: Male rats were assigned to either an untreated or estrogen-treated group. In the treated group, estrogen was delivered for 2 weeks via a subcutaneous implanted pellet containing 17β-estradiol. A mixed population of cardiac inflammatory cells, including T-lymphocytes (about 70%, macrophages (about 12%, and mast cells (about 12%, was isolated from each rat and cultured in a Boyden chamber with cardiac fibroblasts from untreated adult male rats for 24 hours. To examine if tumor necrosis factor-alpha (TNF-α produced by inflammatory cells represents a mechanism contributing to the stimulatory effects of inflammatory cells on cardiac fibroblasts, inflammatory cells from the untreated group were incubated with cardiac fibroblasts in a Boyden chamber system for 24 hours in the presence of a TNF-α -neutralizing antibody. Cardiac fibroblasts were also incubated with 5 ng/mL of TNF-α for 24 hours. Fibroblast proliferation, collagen synthesis, matrix metalloproteinase activity, β1 integrin protein levels, and the ability of fibroblasts to contract collagen gels were determined in all groups and statistically compared via one-way analysis of variance. Results: Inflammatory cells from the

  12. Role of the intercalated disc in cardiac propagation and arrhythmogenesis

    OpenAIRE

    Kleber, Andre G.; Saffitz, Jeffrey E.

    2014-01-01

    This review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the “intercalated disc.”The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called “electrical u...

  13. CARDIAC AMYLOIDOSIS IN A PATIENT WITH MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Parathan

    2015-10-01

    Full Text Available Cardiac amyloidosis is a rare disorder, which is characterised by the extra cellular deposition of amyloid, a protein polysaccharide complex in the heart. This infiltrative cardiomyopathy presents with restrictive heart failure. We report a 58 year old male who pr esented with macroglossia, proteinuria and heart failure. His detailed evaluation revealed multiple myeloma with concurrent Primary (AL amyloidosis. This case report is to highlight the occurrence of cardiac amyloidosis and multiple myeloma which are two separate plasma cell dyscrasias which have presented together.

  14. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    OpenAIRE

    Yali Liu; Dan Su; Ling Zhang; Shaofeng Wei; Kuangyi Liu; Mi Peng; Hanyun Li; Yonggui Song

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower...

  15. A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease

    Science.gov (United States)

    Marcsa, Boglárka; Dénes, Réka; Vörös, Krisztina; Rácz, Gergely; Sasvári-Székely, Mária; Rónai, Zsolt; Törő, Klára; Keszler, Gergely

    2015-01-01

    Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. PMID:26146998

  16. Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

    Science.gov (United States)

    Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

    2016-07-01

    Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage. PMID:26089164

  17. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that...... they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The...

  18. The correlation of ECHO findings of right cardiac pathologies with BNP, uric acid, and CRP in OSAS

    OpenAIRE

    ARAZ*, Ömer; UÇAR, Elif YILMAZEL; DEĞİRMENCİ, Hüsnü; PULUR, Didem

    2014-01-01

    Right cardiac pathologies develop in patients with obstructive sleep apnea syndrome (OSAS) and in most patients there are no symptoms in the early stages of right cardiac disorders. We aimed to evaluate a possible relationship between B-type natriuretic peptide (BNP), blood uric acid, C-reactive protein (CRP), and the right cardiac pathologies in patients with OSAS, and the role of these parameters in the management of patients with OSAS. Materials and methods: A total of 98 subjects, 31 (31...

  19. Trends in Cardiac Pacemaker Batteries

    Directory of Open Access Journals (Sweden)

    Venkateswara Sarma Mallela

    2004-10-01

    Full Text Available Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future.

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

    Science.gov (United States)

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

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function. PMID:17284482

  1. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  2. Electrospun nanofibrous sheets of collagen/elastin/polycaprolactone improve cardiac repair after myocardial infarction.

    Science.gov (United States)

    Liu, Yang; Xu, Yachen; Wang, Zhenhua; Wen, Dezhong; Zhang, Wentian; Schmull, Sebastian; Li, Haiyan; Chen, Yao; Xue, Song

    2016-01-01

    Electrospun nanofibrous sheets get increasing attention in myocardial infarction (MI) treatment due to their good cytocompatibility to deliver transplanted stem cells to infarcted areas and due to mechanical characteristics to support damaged tissue. Cardiac extracellular matrix is essential for implanted cells since it provides the cardiac microenvironment. In this study, we hypothesized high concentrations of cardiac nature protein (NP), namely elastin and collagen, in hybrid polycaprolactone (PCL) electrospun nanofibrous sheets could be effective as cardiac-mimicking patch. Optimal ratio of elastin and collagen with PCL in electrospun sheets (80% NP/PCL) was selected based on cytocompatibility and mechanical characteristics. Bone-marrow (BM) c-kit(+) cells anchoring onto NP/PCL sheets exhibited increased proliferative capacity compared with those seeded on PCL in vitro. Moreover, we examined the improvement of cardiac function in MI mice by cell-seeded cardiac patch. Green Fluorescent Protein (GFP)-labeled BM c-kit(+) cells were loaded on 80% NP/PCL sheets which was transplanted into MI mice. Both 80% NP/PCL and c-kit(+)-seeded 80% NP/PCL effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. C-kit(+)-seeded 80% NP/PCL was even superior to the 80% NP/PCL alone and both superior to PCL. GFP(+) cells were identified both in the sheets and local infarcted area where transplanted cells underwent cardiac differentiation after 4 weeks. To the best of our knowledge, this is the first report that sheets with high concentrations of nature proteins loaded with BM c-kit(+) cells might be a novel promising candidate for tissue-engineered cardiac patch to improve cardiac repair after MI. PMID:27186292

  3. SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in Marathon Runners

    Directory of Open Access Journals (Sweden)

    George D. Wilson

    2012-01-01

    Full Text Available Purpose. To utilize proteomics to discover proteins associated with significant cardiac magnetic resonance imaging (MRI changes in marathon runners. Methods. Serum from 25 runners was analyzed by surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Proteomic profiles were compared in serum samples obtained prior to the race, at the finish line and within 7 hours after race to identify dynamic proteins correlated with cardiac MRI changes. Results. 693 protein/peptide clusters were identified using two ProteinChip surface chemistries and, of these, 116 were significantly different between the three time points. We identified 7 different patterns of protein expression change within the runners and 5 prerace protein peaks, 16 finish-line protein levels, and 15 postrace proteins which were correlated with significant postrace cardiac MRI changes. Conclusions. This study has identified baseline levels of proteins which may be predictive of risk of significant cardiac damage following a marathon race. Preliminary identification of the significant proteins suggested the involvement of cytokines and other proteins involved in stress and inflammatory response.

  4. Cardiac perioperative complications in noncardiac surgery

    OpenAIRE

    Radovanović Dragana; Kolak Radmila; Stokić Aleksandar; Radovanović Zoran; Jovanović Gordana

    2008-01-01

    Anesthesiologists are confronted with an increasing population of patients undergoing noncardiac surgery who are at risk for cardiac complications in the perioperative period. Perioperative cardiac complications are responsible for significant mortality and morbidity. The aim of the present study was to determine the incidence of perioperative (operative and postoperative) cardiac complications and correlations between the incidence of perioperative cardiac complications and type of surgical ...

  5. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy; Catalán, Mabel; Vivar, Raúl; Ayala, Pedro; Humeres, Claudio; Aránguiz, Pablo [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); García, Lorena [Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile (Chile); Díaz-Araya, Guillermo, E-mail: gadiaz@ciq.uchile.cl [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)

    2013-10-15

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  6. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

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

    Science.gov (United States)

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

    2016-01-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes. PMID:27350339

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

    Science.gov (United States)

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

    2016-07-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes. PMID:27350339

  9. Growth hormone and risk for cardiac tumors in Carney complex.

    Science.gov (United States)

    Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A

    2016-09-01

    Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor. PMID:27535175

  10. Azelnidipine protects myocardium in hyperglycemia-induced cardiac damage

    Directory of Open Access Journals (Sweden)

    Puranik Amrutesh S

    2010-12-01

    Full Text Available Abstract Background Azelnidipine (AZL, a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, however, its effect on hyperglycemia-induced cardiac damage has not been studied. Methods This study examined the effect of AZL on circulating markers of cardiac damage, altered lipid and cytokines profile and markers of oxidative stress including homocysteine in diabetic rats. Results STZ induced diabetes caused a significant increase in blood glucose levels. It also resulted in an increase in the levels of homocysteine and cardiac damage markers, like Troponin-1, CK-MB, CK-NAC, uric acid, LDH and alkaline phosphatase. Moreover, there was an increase in the levels of proinflammatory cytokines like TNF-α, IFN-γ, and TGF-β and decrease in the levels of IL-4 and IL-10. Additionally, there was increase in the levels of cholesterol, triglycerides, LDL, VLDL and a decrease in HDL in these animals. There was an altered antioxidant enzyme profile which resulted in a notable increase in the levels of oxidative stress markers like lipid peroxides, nitric oxide and carbonylated proteins. Compared with the untreated diabetic rats, AZL treatment significantly reduced the levels of troponin-1 (P Conclusion Our results indicate that AZL treatment can reduce the risk of hyperglycemia induced metabolic disorders and its role can be further extended to explore its therapeutic potential in diabetic patients with cardiac complications.

  11. Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures.

    Science.gov (United States)

    Parameswaran, Sreejit; Sharma, Rajendra K

    2016-09-01

    Cardiac tissue contains a heterogeneous population of cardiomyocytes and nonmyocyte population especially fibroblasts. Fibroblast differentiation into adipogenic lineage is important for fat accumulation around the heart which is important in cardiac pathology. The differentiation in fibroblast has been observed both spontaneously and due to increased insulin stimulation. The present study aims to observe the effect of insulin in adipogenic differentiation of cardiac cells present in primary murine cardiomyocyte cultures. Oil Red O (ORO) staining has been used for observing the lipid accumulations formed due to adipogenic differentiation in murine cardiomyocyte cultures. The accumulated lipids were quantified by ORO assay and normalized using protein estimation. The lipid accumulation in cardiac cultures did not increase in presence of insulin. However, addition of other growth factors like insulin-like growth factor 1 and epidermal growth factor promoted adipogenic differentiation even in the presence of insulin and other inhibitory molecules such as vitamins. Lipid accumulation also increased in cells grown in media without insulin after an initial exposure to insulin-containing growth media. The current study adds to the existing knowledge that the insulin by itself cannot induce adipogenic induction in the cardiac cultures. The data have significance in the understanding of cardiovascular health especially in diabetic patients. PMID:27574386

  12. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

    Directory of Open Access Journals (Sweden)

    Bernardo A. Petriz

    2014-01-01

    Full Text Available Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.

  13. Cardiac catheterization and angiography. Third edition

    International Nuclear Information System (INIS)

    This book discusses the papers on cardiac catheterization and angiography. The topics covered are: historical perspective and present practice of cardiac catheterization; angiography principles and utilization of radiologic and cineangiographic equipment; complications, incidence and prevention of side effects of cardiac catheterization; techniques; blood flow measurement of heart; pressure measurement; diagnostic techniques of angiography; special catheter techniques; coronary angiography, temporary and permanent pacemakers, potential role of lasers in the cardiac catheterization and evaluation of cardiac function

  14. Antifibrotic therapies to control cardiac fibrosis

    OpenAIRE

    Fan, Zhaobo; Guan, Jianjun

    2016-01-01

    Cardiac fibrosis occurs naturally after myocardial infarction. While the initially formed fibrotic tissue prevents the infarcted heart tissue from rupture, the progression of cardiac fibrosis continuously expands the size of fibrotic tissue and causes cardiac function decrease. Cardiac fibrosis eventually evolves the infarcted hearts into heart failure. Inhibiting cardiac fibrosis from progressing is critical to prevent heart failure. However, there is no efficient therapeutic approach curren...

  15. Robotic Applications in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alan P. Kypson

    2008-11-01

    Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

  16. Cardiac manifestations in systemic sclerosis

    Institute of Scientific and Technical Information of China (English)

    Sevdalina; Lambova

    2014-01-01

    Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.

  17. Computational Modeling of Cardiac Electromechanics

    OpenAIRE

    Krishnamoorthi, Shankarjee

    2013-01-01

    Cardiac arrhythmias are a leading cause of death worldwide. Notably, the electrophysiologiy and microstructural requirements for a fatal ventricular arrhythmia remain incompletely understood, thereby the treatment remains largely empirical. Standard antiarrhythmic drug therapy has failed to reduce, and in some instances has increased, the incidence of Sudden Cardiac Death (SCD). Hence, a more complete understanding of the mechanisms that foment a fatal arrhythmia is needed and computational m...

  18. Cardiac Biomarkers in Hyperthyroid Cats

    OpenAIRE

    Sangster, Jodi Kirsten

    2013-01-01

    Background: Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT-proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been as extensively investigated in hyperthyroidism.Hypothesis: Plasma NT-proBNP and cTNI concentrations are higher in cats with primary cardiac disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats.Animals: Twenty-three hyperthyr...

  19. Current trends in cardiac rehabilitation

    OpenAIRE

    Dafoe, W; Huston, P

    1997-01-01

    Cardiac rehabilitation can reduce mortality and morbidity for patients with many types of cardiac disease cost-effectively, yet is generally underutilized. Rehabilitation is helpful not only for patients who have had a myocardial infarction but also for those with stable angina or congestive heart failure or those who have undergone myocardial revascularization procedures, a heart transplant or heart valve surgery. The beneficial effects of rehabilitation include a reduction in the rate of de...

  20. An overview of cardiac morphogenesis.

    OpenAIRE

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-01-01

    International audience Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In th...

  1. Gastrointestinal Complications and Cardiac Surgery

    OpenAIRE

    Allen, Sara J.

    2014-01-01

    Gastrointestinal (GI) complications are an uncommon but potentially devastating complication of cardiac surgery. The reported incidence varies between .3% and 5.5% with an associated mortality of .3–87%. A wide range of GI complications are reported with bleeding, mesenteric ischemia, pancreatitis, cholecystitis, and ileus the most common. Ischemia is thought to be the main cause of GI complications with hypoperfusion during cardiac surgery as well as systemic inflammation, hypothermia, drug ...

  2. Cardiac abnormalities after subarachnoid hemorrhage

    OpenAIRE

    Bilt, I.A.C. van der

    2016-01-01

    Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart Syndrome) that has been described after acute stress. It is a reversible cardiac dysfunction with distinct imaging features(the echocardiographic or left ventricular angiographic image resembles a Tak...

  3. Isolated heart transplantation for familial transthyretin (TTR) V122I cardiac amyloidosis.

    Science.gov (United States)

    Thenappan, Thenappan; Fedson, Savitri; Rich, Jonathan; Murks, Catherine; Husain, Aliya; Pogoriler, Jennifer; Anderson, Allen S

    2014-06-01

    Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation. Abbreviations MMF mycophenolate mofetil NYHA New York Heart Association TTR transthyretin VE minute ventilation. PMID:24818650

  4. FGF21 and cardiac physiopathology

    Directory of Open Access Journals (Sweden)

    Anna ePlanavila

    2015-08-01

    Full Text Available The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21 production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

  5. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  6. Cardiac MRI in suspected myocarditis

    International Nuclear Information System (INIS)

    Purpose: To evaluate the potential of ECG-gated breath-hold MRI in diagnosing acute myocardidits. Material and methods: Cardiac MRI was performed on 21 consecutive patients with suspected myocarditis. ECG-gated breath-hold T2-weighted images with fat suppression were acquired in 3 standard views. T1-weighted imaging (FLASH) was performed 10 min after IV administration of Gd-DTPA. Laboratory data included creatine kinase, troponin T and serological tests, ECG findings and echocardiography. Imaging findings were retrospectively compared to the discharge diagnoses. Signal alterations were semiquantitatively classified. Results: Acute myocarditis was diagnosed in 9 patients and cardiac sarcoidosis in 2 patients. Late enhancement was observed in 4 patients with acute myocarditis and in both patients with cardiac sarcoidosis. Semiquantitative evaluation revealed 9 true positive, 9 true negative, 1 false positive and 2 false negative results. Conclusion: Cardiac MRI has the potential to detect acute myocarditis and to diagnose cardiac sarcoidosis. Late enhancement of Gd-DTPA can be found in both viral myocarditis and cardiac sarcoidosis. (orig.)

  7. Cardiac imaging. A multimodality approach

    International Nuclear Information System (INIS)

    An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

  8. Cardiac involvement in myotonic dystrophy

    DEFF Research Database (Denmark)

    Lund, Marie; Diaz, Lars Jorge; Ranthe, Mattis Flyvholm;

    2014-01-01

    genetic testing for DM1. Information on incident cardiac diseases was obtained from the NPR. We estimated standardized incidence ratios (SIRs) of cardiac disease compared with the background population, overall and according to selected diagnostic subgroups (cardiomyopathy, heart failure, conduction...... disorders, arrhythmias, and device implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95% confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59 (95% CI: 2.03-3.25). For a cardiac disease...... belonging to the selected subgroups, the risk was particularly high in the first year after DM diagnosis [SIR 15.4 (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR 6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20-39 years: SIR 18.1 (95% CI: 12...

  9. Anthracycline-induced cardiac injury using a cardiac cell line: potential for gene therapy studies.

    Science.gov (United States)

    L'Ecuyer, T; Horenstein, M S; Thomas, R; Vander Heide, R

    2001-11-01

    Anthracyclines are effective antitumor agents whose chief limitation has been cardiotoxicity directly related to free radical production. Therefore, strategies designed to selectively overexpress antioxidant proteins in the heart could protect against drug-induced toxicity and allow higher doses of chemotherapy. However, to date an adequate cardiac model system that is susceptible to anthracycline injury and can express foreign genes in a controlled fashion has been lacking. Developing a cardiac model system would permit examination of the relationship between the expression level of a potentially protective foreign gene and the degree of protection from injury. In this study we have examined the potential of the H9C2 rat cardiac myocyte cell line in this regard. H9C2 cells differentiate in a reproducible fashion, as shown by progressive increases in muscle tropomyosin-expressing cells, the organization of this thin filament protein, and the percentage of muscle cells contained within myotubes. Exposure of this cell line to the anthracycline doxorubicin produces cell injury as indicated by release of the intracellular enzyme lactate dehydrogenase into the culture medium. This injury is preceded by generation of reactive oxygen species, indicated by fluorescence after loading with carboxy-dichlorodihydrofluorescein diacetate. Stable transfection of H9C2 cells with a plasmid producing a tetracycline transactivator protein allows foreign genes to be expressed at a level tightly controlled by the concentration of tetracycline in the culture medium. Since H9C2 cells differentiate, can be injured by anthracycline exposure, and can express foreign genes at controllable levels, this is a suitable system in which to design genetic approaches to prevent this important clinical problem. PMID:11708868

  10. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  11. Cardiac output during exercise

    DEFF Research Database (Denmark)

    Siebenmann, C; Rasmussen, P.; Sørensen, H.;

    2015-01-01

    Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from the...... right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2  = 12%). While all four methods reported a...... progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0.001] and...

  12. Activation of GPR30 inhibits cardiac fibroblast proliferation.

    Science.gov (United States)

    Wang, Hao; Zhao, Zhuo; Lin, Marina; Groban, Leanne

    2015-07-01

    The incidence of left ventricular diastolic dysfunction significantly increases in postmenopausal women suggesting the association between estrogen loss and diastolic dysfunction. The in vivo activation of G protein-coupled estrogen receptor (GPR30) attenuates the adverse effects of estrogen loss on cardiac fibrosis and diastolic dysfunction in mRen2.Lewis rats. This study was designed to address the effects of GPR30 on cardiac fibroblast proliferation in rats. The expression of GPR30 in cardiac fibroblasts isolated from adult Sprague-Dawley rats was confirmed by RT-PCR, Western blot analysis, and immunofluorescence staining. Results from BrdU incorporation assays, cell counting, carboxyfluorescein diacetate succinimidyl ester labeling in conjunction with flow cytometry, and Ki-67 staining showed that treatment with G1, a specific agonist of GPR30, inhibited cardiac fibroblast proliferation in a dose-dependent manner, which was associated with decreases in CDK1 and cyclin B1 protein expressions. In the GPR30-KO cells, BrdU incorporation, and CDK1 and cyclin B1 expressions significantly increased when compared to GPR30-intact cells. G1 had no effect on BrdU incorporation, CDK1 and cyclin B1 mRNA levels in GPR30-KO cells. In vivo studies showed increases in CDK1 and cyclin B1 mRNA levels, Ki-67-positive cells, and the immunohistochemistry staining of vimentin, a fibroblast marker, in the left ventricles from ovariectomized mRen2.Lewis rats versus hearts from ovary-intact littermates; 2 weeks of G1 treatment attenuated these adverse effects of estrogen loss. This study demonstrates that GPR30 is expressed in rat cardiac fibroblasts, and activation of GPR30 limits proliferation of these cells likely via suppression of the cell cycle proteins, cyclin B1, and CDK1. PMID:25893735

  13. Cardiac Na+ Current Regulation by Pyridine Nucleotides

    Science.gov (United States)

    Liu, Man; Sanyal, Shamarendra; Gao, Ge; Gurung, Iman S.; Zhu, Xiaodong; Gaconnet, Georgia; Kerchner, Laurie J.; Shang, Lijuan L.; Huang, Christopher L-H.; Grace, Andrew; London, Barry; Dudley, Samuel C.

    2009-01-01

    Rationale Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na+ current (INa) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in nicotinamide adenine dinucleotide (NAD)-dependent energy metabolism. Objective Therefore, we tested whether NAD(H) could regulate human cardiac sodium channels (Nav1.5). Methods and Results HEK293 cells stably expressing Nav1.5 and rat neonatal cardiomyocytes were used. The influence of NADH/NAD+ on arrhythmic risk was evaluated in wild-type or SCN5A+/− mouse heart. A280V GPD1-L caused a 2.48 ± 0.17-fold increase in intracellular NADH level (P<0.001). NADH application or co-transfection with A280V GPD1-L resulted in decreased INa (0.48 ± 0.09 or 0.19 ±0.04 of control group, respectively; P<0.01), which was reversed by NAD+, chelerythrine, or superoxide dismutase (SOD). NAD+ antagonism of the Na+ channel downregulation by A280V GPD1-L or NADH was prevented by a protein kinase A (PKA) inhibitor, PKAI6–22. The effects of NADH and NAD+ were mimicked by a phorbol ester and forskolin, respectively. Increasing intracellular NADH was associated with an increased risk of ventricular tachycardia (VT) in wild-type mouse hearts. Extracellular application of NAD+ to SCN5A+/− mouse hearts ameliorated the risk of VT. Conclusions Our results show that Nav1.5 is regulated by pyridine nucleotides, suggesting a link between metabolism and INa. This effect required protein kinase C (PKC) activation and was mediated by oxidative stress. NAD+ could prevent this effect by activating PKA. Mutations of GPD1-L may downregulate Nav1.5 by altering the oxidized to reduced NAD(H) balance. PMID:19745168

  14. Graphene induces spontaneous cardiac differentiation in embryoid bodies

    Science.gov (United States)

    Ahadian, Samad; Zhou, Yuanshu; Yamada, Shukuyo; Estili, Mehdi; Liang, Xiaobin; Nakajima, Ken; Shiku, Hitoshi; Matsue, Tomokazu

    2016-03-01

    Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac differentiation of EBs, which has potential cell therapy and tissue regeneration applications.Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac

  15. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    Several clinical trials have shown the beneficial effects of statins in the prevention of coronary heart disease. Additionally, statins promote apoptosis in vascular smooth muscle cells, in renal tubular epithelial cells and also in a variety of cell lines; yet, the effects of statins on cardiac fibroblast and myofibroblast, primarily responsible for cardiac tissue healing are almost unknown. Here, we investigated the effects of simvastatin on cardiac fibroblast and myofibroblast viability and studied the molecular cell death mechanism triggered by simvastatin in both cell types. Methods: Rat neonatal cardiac fibroblasts and myofibroblasts were treated with simvastatin (0.1-10 μM) up to 72 h. Cell viability and apoptosis were evaluated by trypan blue exclusion method and by flow cytometry, respectively. Caspase-3 activation and Rho protein levels and activity were also determined by Western blot and pull-down assay, respectively. Results: Simvastatin induces caspase-dependent apoptosis of cardiac fibroblasts and myofibroblasts in a concentration- and time-dependent manner, with greater effects on fibroblasts than myofibroblasts. These effects were prevented by mevalonate, farnesylpyrophosphate and geranylgeranylpyrophosphate, but not squalene. These last results suggest that apoptosis was dependent on small GTPases of the Rho family rather than Ras. Conclusion: Simvastatin triggered apoptosis of cardiac fibroblasts and myofibroblasts by a mechanism independent of cholesterol synthesis, but dependent of isoprenilation of Rho protein. Additionally, cardiac fibroblasts were more susceptible to simvastatin-induced apoptosis than cardiac myofibroblasts. Thus simvastatin could avoid adverse cardiac remodeling leading to a less fibrotic repair of the damaged tissues. - Research Highlights: → Simvastatin decreases CF and CMF viability independent of cholesterol synthesis. → Simvastatin induces CF and CMF apoptosis in a caspase-dependent manner being CMF more resistant

  16. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin Ⅱ-induced cardiac diastolic dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Yu-qiong LI; Xiao-bo LI; Shu-jie GUO; Shao-li CHU; Ping-jin GAO; Ding-liang ZHU; Wen-quan NIU

    2013-01-01

    Aim:To investigate whether apocynin,a NADPH oxidase inhibitor,produced cardioproteictive effects in Ang Ⅱ-induced hypertensive mice,and to elucidate the underlying mechanisms.Methods:C57BL/6 mice were subcutaneously infused Ang Ⅱ for 4 weeks to mimic cardiac remodeling and fibrosis.Concomitantly the mice were administered apocynin (100 mg· kg-1·d-1) or/and the aldosterone receptor blocker eplerenone (200 mg·kg-1d-1) via gavage for 4 weeks.Systolic blood pressure (SBP) and heart rate were measured,and transthoracic echocardiography was performed.For in vitro study,cardiac fibroblasts were treated with Ang Ⅱ (10 7 mol/L) in the presence of apocynin (105 mol/L) or/and eplerenone (105 mol/L).Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells.Results:Both apocynin and eplerenone significantly decreased SBP,and markedly improved diastolic dysfunction in Ang Ⅱ-induced hypertensive mice,accompanied with ameliorated oxidative stress and cardiac fibrosis.In the Ang Ⅱ-treated cardiac fibroblasts,the expression levels of NOX4 and OPN proteins were markedly upregulated.Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang Ⅱ-treated cells.In all the experiments,apocynin and eplerenone produced comparable effects.Co-administration of the two agents did not produce synergic effects.Conclusion:Apocynin produces cardioproteictive effects comparable to those of eplerenone.The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.

  17. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors.

    Science.gov (United States)

    Islas, Jose Francisco; Liu, Yu; Weng, Kuo-Chan; Robertson, Matthew J; Zhang, Shuxing; Prejusa, Allan; Harger, John; Tikhomirova, Dariya; Chopra, Mani; Iyer, Dinakar; Mercola, Mark; Oshima, Robert G; Willerson, James T; Potaman, Vladimir N; Schwartz, Robert J

    2012-08-01

    Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian Ciona, which is dependent upon the transcription factors Ci-ets1/2 and Ci-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR(+). However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca(2+) transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis. PMID:22826236

  18. Cardiac and inflammatory biomarkers do not correlate with volume of heart or lung receiving radiation

    International Nuclear Information System (INIS)

    Thoracic and cardiac irradiation increases the risk of pulmonary and cardiovascular disease. In addition, radiation, often in combination with chemotherapy, can cause treatment-related pneumonitis. Previously, we showed that the common marker for cardiac damage, troponin T, was not elevated by chemoradiation [Lung Cancer 62:351–355, 2008]. In this study, we explore whether dose-volume metrics and biomarkers for cardiac damage, inflammation or angiogenesis could identify patients receiving thoracic radiation who would later have cardiac or pulmonary complications. To this end, we quantified cardiac biomarkers including c-reactive protein (cRP) as well as a panel of angiogenic and inflammatory molecules in thirty patients who received radiation therapy to the thorax with or without concurrent chemotherapy between May 2006 and May 2007. Serum was collected at baseline, 2 weeks into radiation treatment and at the completion of radiation therapy. Heart and lung dosimetric parameters and clinical risk factors were also examined, along with the monitoring of adverse pulmonary and cardiac events during follow-up. Contrary to our hypothesis, there was no correlation between serum biomarker levels and cardiac radiation dose. Similarly there was little association between lung dose-volume metrics and inflammatory or angiogenic biomarkers. Furthermore, there was no correlation with serum biomarkers and adverse pulmonary or cardiovascular events. Based on these data, acute elevations in serum biomarkers of cardiac damage, inflammation or angiogenesis should not be attributed to thoracic (chemo)radiation and elevations in such biomarkers of tissue damage should be further evaluated

  19. Computed tomography of cardiac pseudotumors and neoplasms.

    Science.gov (United States)

    Anavekar, Nandan S; Bonnichsen, Crystal R; Foley, Thomas A; Morris, Michael F; Martinez, Matthew W; Williamson, Eric E; Glockner, James F; Miller, Dylan V; Breen, Jerome F; Araoz, Philip A

    2010-07-01

    Important features of cardiac masses can be clearly delineated on cardiac computed tomography (CT) imaging. This modality is useful in identifying the presence of a mass, its relationship with cardiac and extracardiac structures, and the features that distinguish one type of mass from another. A multimodality approach to the evaluation of cardiac tumors is advocated, with the use of echocardiography, CT imaging and magnetic resonance imaging as appropriately indicated. In this article, various cardiac masses are described, including pseudotumors and true cardiac neoplasms, and the CT imaging findings that may be useful in distinguishing these rare entities are presented. PMID:20705174

  20. Cardiac output monitoring

    Directory of Open Access Journals (Sweden)

    Mathews Lailu

    2008-01-01

    Full Text Available Minimally invasive and non-invasive methods of estimation of cardiac output (CO were developed to overcome the limitations of invasive nature of pulmonary artery catheterization (PAC and direct Fick method used for the measurement of stroke volume (SV. The important minimally invasive techniques available are: oesophageal Doppler monitoring (ODM, the derivative Fick method (using partial carbon dioxide (CO 2 breathing, transpulmonary thermodilution, lithium indicator dilution, pulse contour and pulse power analysis. Impedance cardiography is probably the only non-invasive technique in true sense. It provides information about haemodynamic status without the risk, cost and skill associated with the other invasive or minimally invasive techniques. It is important to understand what is really being measured and what assumptions and calculations have been incorporated with respect to a monitoring device. Understanding the basic principles of the above techniques as well as their advantages and limitations may be useful. In addition, the clinical validation of new techniques is necessary to convince that these new tools provide reliable measurements. In this review the physics behind the working of ODM, partial CO 2 breathing, transpulmonary thermodilution and lithium dilution techniques are dealt with. The physical and the physiological aspects underlying the pulse contour and pulse power analyses, various pulse contour techniques, their development, advantages and limitations are also covered. The principle of thoracic bioimpedance along with computation of CO from changes in thoracic impedance is explained. The purpose of the review is to help us minimize the dogmatic nature of practice favouring one technique or the other.

  1. Present Researching Approaches and Future Prospects for Treatment of Cardiac Diseases-Integrative Medicine

    Institute of Scientific and Technical Information of China (English)

    Yan Feng; Hao Xu; Yi-Xin Wang; Li-Ping Ma; Da-Zhuo Shi

    2015-01-01

    The pathogenesis of cardiac diseases is very complex and involved in many gene transcription and protein expression. How to effectively treat the diseases has become the hotspot of modern medicine. Accumulating evidences over the past decades on integrative medicine have shown us hopeful future prospects. With the development of modern biomedicine, such as sketch mapping genomic sequence, functional genomics, proteomics and pharmacogenetics, more advanced techniques could be applied in elucidating the possibly complicated biological networks, or complex pathological and physiological mechanisms underlying cardiac diseases, by which integrative medicine will also bring out some new and more effective strategies in the treatment of cardiac diseases.

  2. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  3. Vitamin D and Cardiac Differentiation.

    Science.gov (United States)

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  4. Cardiac factors in orthostatic hypotension

    Science.gov (United States)

    Löllgen, H.; Dirschedl, P.; Koppenhagen, K.; Klein, K. E.

    Cardiac function is determined by preload, afterload, heart rate and contractility. During orthostatic stress, the footward blood shift is compensated for by an increase of afterload. LBNP is widely used to analyze effects of volume displacement during orthostatic stress. Comparisons of invasive ( right heart catheterization) and non-invasive approach (echocardiography) yielded similar changes. Preload and afterload change with graded LBNP, heart rate increases, and stroke volume and cardiac output decrease. Thus, the working point on the left ventricular function curve is shifted to the left and downward, similar to hypovolemia. However, position on the Frank-Starling curve, the unchanged ejection fraction, and the constant Vcf indicate a normal contractile state during LBNP. A decrease of arterial oxygen partial pressure during LBNP shwos impaired ventilation/perfusion ratio. Finally, LBNP induced cardiac and hemodynamic changes can be effectively countermeasured by dihydroergotamine, a potent venoconstrictor. Comparison of floating catheter data with that of echocardiography resulted in close correlation for cardiac output and stroke volume. In addition, cardiac dimensions changed in a similar way during LBNP. From our findings, echocardiography as a non-invasive procedure can reliably used in LBNP and orthostatic stress tests. Some informations can be obtained on borderline values indicating collaps or orthostatic syncope. Early fainters can be differentiated from late fainters by stroke volume changes.

  5. Cardiac Penetrating Injuries and Pseudoaneurysm

    Institute of Scientific and Technical Information of China (English)

    CHEN Shifeng

    2002-01-01

    Objective To discuss the early diagnosis and treatment of cardiac penetrating injuries and pseudoaneurysm. Methods 18 cases of cardiac penetrating injuries, in which 2 cases were complicated with pseudoaneurysm, were diagnosed by emergency operation and color Doppler echocardiography between May 1973 and Dec. 2001 in our hospital. The basis for emergency operation is the injured path locating in cardiac dangerous zone, severe shock or pericardial tamponade. ResultsAmong 18 cases of this study, 17 cases underwent emergency operation. During the operation, 11 cases were found injured in right ventricle, 2 cases were found injured in right atrium, 1 case was found injured in pulmonary artery,4 cases were found injured in left ventricle, 2 cases were found complicated with pseudoaneurysm. 17cases underwent cardiac repair including 1 case of rupture of aneurysm. 1 case underwent elective aneurysm resection. In whole group, 15 cases survived(83.33% ), 3 cases died( 16.67%). The cause of death is mainly hemorrhagic shock. Conclusion Highly suspicious cardiac penetrating injuries or hemopericaridium should undergo direct operative exploration. Pseudoaneurysm should be resected early,which can prevent severe complications.

  6. Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

    OpenAIRE

    Hesse, A; Altland, K; Linke, R P; M.R. Almeida; Saraiva, M.J.; Steinmetz, A; Maisch, B

    1993-01-01

    Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriur...

  7. Comparison of three early biomarkers for acute kidney injury after cardiac surgery under cardiopulmonary bypass

    OpenAIRE

    Moriyama, Takahiro; Hagihara, Shintaro; Shiramomo, Toko; Nagaoka, Misaki; Iwakawa, Shohei; Kanmura, Yuichi

    2016-01-01

    Background Acute kidney injury (AKI) is a serious complication after cardiac surgery, being associated with a high mortality. We assessed three urinary biomarkers, L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen, which are elevated through different mechanisms, and investigated which of these biomarkers was the earliest and most useful indicator of AKI after cardiac surgery. Methods This study was a prospective observational s...

  8. 心型脂肪酸结合蛋白、肌钙蛋白Ⅰ与脑卒中继发性肺栓塞的关系%Association between heart-type fatty acid binding protein, cardiac tro-poninⅠand stroke-associated pulmonary embolism

    Institute of Scientific and Technical Information of China (English)

    韩芳; 张伟东; 廖晓凌; 王拥军

    2014-01-01

    Objective To investigate the diagnosis and prognostic value of heart-type fatty acid binding protein com-bined cardiac troponin Ⅰ in stroke-associated pulmonary embolism patients. Methods 150 patients with stroke-asso-ciated pulmonary embolism (study group) and 150 patients of stroke without pulmonary embolism (control group) from January 2011 to April 2014 in Luhe Hospital of Tongzhou District in Beijing City were selected in this study. The H-FABP and cardiac troponin Ⅰ of patients in two groups before treatment and those of the study group after treatment were detected and compared. Results The levels of plasma H-FABP and cardiac troponin Ⅰ of patients before treat-ment in study group [(9.52±2.67), (0.15±0.09) μg/L ] were higher than those of the control group [(3.87±2.96), (0.05±0.03) μg/L], the differences were statistically significant (P<0.05).After treatment, the levels of plasma H-FABP and cardiac troponinⅠ in study group [(5.51±1.97), (0.08±0.03) μg/L] were decreased than pretreatment, the differences were statistically significant (P<0.05). Conclusion The level of H-FABP and cardiac troponinⅠ increasing obviously in stroke-associated pulmonary embolism, and the detection of the two indexs can be helpful for the disease diagnosis and the access of short-time prognosis.%目的:探讨心型脂肪酸结合蛋白(H-FABP)联合肌钙蛋白Ⅰ(cTnⅠ)对脑卒中继发性肺栓塞患者早期诊断及判断预后的价值。方法选取2011年1月~2014年4月北京市通州区潞河医院收治的150例脑卒中继发性肺栓塞患者(研究组)及单纯脑卒中患者150例(对照组)。检测并比较治疗前两组及研究组治疗前后H-FABP、cTnⅠ水平。结果治疗前研究组H-FABP [(9.52±2.67)μg/L]及cTnⅠ[(0.15±0.09)μg/L]水平明显高于对照组[(3.87±2.96)、(0.05±0.03)μg/L],差异均有统计学意义(P<0.05);治疗后研究组患者血浆H-FABP、cTnⅠ水平分别为(5.51±1.97)、(0.08±0.03)

  9. TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy.

    Science.gov (United States)

    Ghaoui, Roula; Benavides, Tatiana; Lek, Monkol; Waddell, Leigh B; Kaur, Simranpreet; North, Kathryn N; MacArthur, Daniel G; Clarke, Nigel F; Cooper, Sandra T

    2016-08-01

    TorsinA-interacting protein 1 (TOR1AIP1) gene is a novel gene that has recently been described to cause limb-girdle muscular dystrophy (LGMD) with mild dilated cardiomyopathy. We report a family with mutations in TOR1AIP1 where the striking clinical feature is severe cardiac failure requiring cardiac transplant in two siblings, in addition to musculoskeletal weakness and muscular dystrophy. We demonstrate an absence of TOR1AIP1 protein expression in cardiac and skeletal muscles of affected siblings. We expand the phenotype of this gene to demonstrate the cardiac involvement and the importance of cardiac surveillance in patients with mutations in TOR1AIP1. PMID:27342937

  10. CT diagnosis of cardiac lipoma

    International Nuclear Information System (INIS)

    Objective: To investigate the application of CT in the diagnosis of cardiac lipoma. Methods: Retrospective analysis of 6 patients with cardiac lipoma confirmed by operation and pathology was done. Four patients had singles slice electron beam CT plain and contrast and movie scan. Two patients had 64-slice CT plain and enhanced scan. Results: (1) One patient was isolated intracavitary lipoma in the right artrium, 1 patient was isolated intrapericardial lipoma and 4 patients were intramural lipomas. Of the 4 intramural lipoma, 2 were infiltrative lipomas located in the left ventricle wall or the right ventricle and septum, 2 patients were isolated in the atrio-ventricular septum. (2) CT and three-dimensional reconstruction could depict the location, shape, size, margin and characteristic fat density of lipoma, indicating the diagnosis and classifications. The displacement of coronary artery, pulmonary inflammation and effusions of pericardium and pleural cavity could also be revealed. Conclusion: Cardiac lipoma can be accurately diagnosed and classified by CT. (authors)

  11. Mechanical Regulation of Cardiac Development

    Directory of Open Access Journals (Sweden)

    HuseyinCagatayYalcin

    2014-08-01

    Full Text Available Mechanical forces are an essential contributor to and unavoidable component of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development.

  12. Complications after cardiac implantable electronic device implantations

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;

    2013-01-01

    Complications after cardiac implantable electronic device (CIED) treatment, including permanent pacemakers (PMs), cardiac resynchronization therapy devices with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter defibrillators (ICDs), are associated with increased patient...

  13. How Is Sudden Cardiac Arrest Diagnosed?

    Science.gov (United States)

    ... heart (a sign of CHD). MUGA Test or Cardiac MRI A MUGA (multiple gated acquisition) test shows how ... create pictures of many parts of your heart. Cardiac MRI (magnetic resonance imaging) is a safe procedure that ...

  14. An update on insertable cardiac monitors

    DEFF Research Database (Denmark)

    Olsen, Flemming J; Biering-Sørensen, Tor; Krieger, Derk W

    2015-01-01

    Continuous cardiac rhythm monitoring has undergone compelling progress over the past decades. Cardiac monitoring has emerged from 12-lead electrocardiograms being performed at the discretion of the treating physician to in-hospital telemetry, Holter monitoring, prolonged external event monitoring...

  15. Sudden Cardiac Arrest (SCA) Risk Assessment

    Science.gov (United States)

    ... Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

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

    Directory of Open Access Journals (Sweden)

    Craig Bolte

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

  17. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    Science.gov (United States)

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions. PMID:26857347

  18. [Progress in the diagnosis and treatment of cardiac amyloidosis].

    Science.gov (United States)

    Jurczyszyn, Artur; Engel, Anna; Rajzer, Marek; Czepiel, Jacek; Mazurs, Grzegorz

    2014-01-01

    The heart is an organ often occupied by various forms of amyloidosis; cardiomyopathies are the leading cause of mortality in patients with amyloidosis. Cardiac amyloidosis is often diagnosed late because of nonspecific symptoms and missed early signs in the imaging routine. A method for treating cardiac amyloidosis depends on the type of amyloid protein. In the treatment of amyloidosis associated with immunoglobulins systemic chemotherapy is used without transplant or stem cell transplantation and in the treatment of familial transthyretin amyloidosis liver transplantation is used. There are still clinical studies on the use of siRNA for the treatment of cardiomyopathy associated with transthy retin amyloidosis, and on the use of amyloid protein stabilizers. The prognosis depends on the type of amyloid protein; worse results observed in the case of light chain amyloidosis. Care support is the cornerstone of treatment; it is expected that advances in cardiac imaging and proteomics positive impact on our ability to diagnosis, prognosis and treatment outcomes of amyloidosis of the heart. PMID:25344976

  19. Cardiac Metastasis from Invasive Thymoma Via the Superior Vena Cava: Cardiac MRI Findings

    International Nuclear Information System (INIS)

    Cardiac tumors are rare, and metastatic deposits are more common than primary cardiac tumors. We present cardiac magnetic resonance imaging (MRI) findings of a 50-year-old woman with invasive thymoma. Cardiac MRI revealed a heterogeneous, lobulated anterior mediastinal mass invading the superior vena cava and extending to the right atrium. In cine images there was no invasion to the right atrial wall.

  20. Pregnancy as a cardiac stress model

    OpenAIRE

    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 witho...

  1. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

  2. Traumatic Tricuspid Regurgitation Following Cardiac Massage

    OpenAIRE

    Na, Sungwon; Nam, Sang Beom; Lee, Yong Kyung; Oh, Young Jun; Kwak, Young-Lan

    2007-01-01

    We report a 66-yr-old male patient who developed tricuspid regurgitation secondary to internal cardiac massage. After uneventful off-pump coronary artery bypass surgery, the subject experienced cardiac arrest in the intensive care unit. External cardiac massage was initiated and internal cardiac massage was performed eventually. A transesophageal echocardiography revealed avulsion of the anterior papillary muscle and chordae to the anterior leaflet after successful cardiopulmonary resuscitati...

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

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl) diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl) diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases. PMID:27281159

  4. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    Science.gov (United States)

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

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

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl) diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl) diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases. PMID:27281159

  6. [Cardiac output monitoring by impedance cardiography in cardiac surgery].

    Science.gov (United States)

    Shimizu, H; Seki, S; Mizuguchi, A; Tsuchida, H; Watanabe, H; Namiki, A

    1990-04-01

    The cardiac output monitoring by impedance cardiography, NCCOM3, was evaluated in adult patients (n = 12) who were subjected to coronary artery bypass grafting. Values of cardiac output measured by impedance cardiography were compared to those by the thermodilution method. Changes of base impedance level used as an index of thoracic fluid volume were also investigated before and after cardiopulmonary bypass (CPB). Correlation coefficient (r) of the values obtained by thermodilution with impedance cardiography was 0.79 and the mean difference was 1.29 +/- 16.9 (SD)% during induction of anesthesia. During the operation, r was 0.83 and the mean difference was -14.6 +/- 18.7%. The measurement by impedance cardiography could be carried out through the operation except when electro-cautery was used. Base impedance level before CPB was significantly lower as compared with that after CPB. There was a negative correlation between the base impedance level and central venous pressure (CVP). No patients showed any signs suggesting lung edema and all the values of CVP, pulmonary artery pressure and blood gas analysis were within normal ranges. From the result of this study, it was concluded that cardiac output monitoring by impedance cardiography was useful in cardiac surgery, but further detailed examinations will be necessary on the relationship between the numerical values of base impedance and the clinical state of the patients. PMID:2362347

  7. Health Literacy Predicts Cardiac Knowledge Gains in Cardiac Rehabilitation Participants

    Science.gov (United States)

    Mattson, Colleen C.; Rawson, Katherine; Hughes, Joel W.; Waechter, Donna; Rosneck, James

    2015-01-01

    Objective: Health literacy is increasingly recognised as a potentially important patient characteristic related to patient education efforts. We evaluated whether health literacy would predict gains in knowledge after completion of patient education in cardiac rehabilitation. Method: This was a re-post observational analysis study design based on…

  8. ROLE OF THE INTERCALATED DISC IN CARDIAC PROPAGATION AND ARRHYTHMOGENESIS

    Directory of Open Access Journals (Sweden)

    Andre Georges Kleber

    2014-10-01

    Full Text Available AbstractThis review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the intercalated disc. The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called electrical uncoupling may either only slow, or additionally stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance. The role of heterogeneous connexin expression, which may be present in disease states, is also discussed. The hypothesis that so-called ephaptic impulse transmission plays a role in heart and can substitute for electrical coupling has been revived recently. Whereas ephaptic transmission can be demonstrated in theoretical simulations, direct experimental evidence has not yet been presented.The second part of this review deals with the interaction of three protein complexes at the intercalated disc: (1 desmosomal and adherers junction proteins, (2 ion channel proteins, and (3 gap junction channels consisting of connexins. Recent work has revealed multiple interactions between these three protein complexes which occur, at least in part, at the level of protein trafficking. Such interactions are likely to play an important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may reveal new therapeutic concepts and targets.

  9. Childhood cancer survivors: cardiac disease & social outcomes

    NARCIS (Netherlands)

    E.A.M. Feijen

    2015-01-01

    The thesis is divided in two parts; Cardiac health problems and healthcare consumption & social outcomes in CCS. The general aims of part 1 creates optimal conditions for the evaluation of cardiac events in 5-year childhood cancer survivors, evaluation of the long term risk of cardiac events, and to

  10. MRI of cardiac rhabdomyoma in the fetus

    Energy Technology Data Exchange (ETDEWEB)

    Kivelitz, Dietmar E.; Muehler, Matthias [Institut fuer Radiologie, Medizinische Fakultaet, Humboldt-Universitaet zu Berlin, Charite, Schumannstrasse 20/21, 10098, Berlin (Germany); Rake, Annett; Chaoui, Rabih [Klinik fuer Gynaekologie und Geburtshilfe, Medizinische Fakultaet, Humboldt-Universitaet zu Berlin, Charite, Schumannstrasse 20/21, 10098, Berlin (Germany); Scheer, Ianina [Klinik fuer Strahlenheilkunde, Abteilung Paediatrische Radiologie, Medizinische Fakultaet, Humboldt-Universitaet zu Berlin, Charite, Schumannstrasse 20/21, 10098, Berlin (Germany)

    2004-08-01

    Primary cardiac tumors are rarely diagnosed in utero and are usually seen on prenatal echocardiography. Cardiac rhabdomyomata can be associated with tuberous sclerosis. Prenatal MRI can be performed to assess associated malformations. This case report illustrates the ability of fetal MRI to image cardiac rhabdomyata and compares it with prenatal and postnatal echocardiography. (orig.)

  11. Telocytes in exercise-induced cardiac growth.

    Science.gov (United States)

    Xiao, Junjie; Chen, Ping; Qu, Yi; Yu, Pujiao; Yao, Jianhua; Wang, Hongbao; Fu, Siyi; Bei, Yihua; Chen, Yan; Che, Lin; Xu, Jiahong

    2016-05-01

    Exercise can induce physiological cardiac growth, which is featured by enlarged cardiomyocyte cell size and formation of new cardiomyocytes. Telocytes (TCs) are a recently identified distinct interstitial cell type, existing in many tissues and organs including heart. TCs have been shown to form a tandem with cardiac stem/progenitor cells in cardiac stem cell niches, participating in cardiac regeneration and repair. Although exercise-induced cardiac growth has been confirmed as an important way to promote cardiac regeneration and repair, the response of cardiac TCs to exercise is still unclear. In this study, 4 weeks of swimming training was used to induce robust healthy cardiac growth. Exercise can induce an increase in cardiomyocyte cell size and formation of new cardiomyocytes as determined by Wheat Germ Lectin and EdU staining respectively. TCs were identified by three immunofluorescence stainings including double labelling for CD34/vimentin, CD34/platelet-derived growth factor (PDGF) receptor-α and CD34/PDGF receptor-β. We found that cardiac TCs were significantly increased in exercised heart, suggesting that TCs might help control the activity of cardiac stem/progenitor cells, cardiomyocytes or endothelial cells. Adding cardiac TCs might help promote cardiac regeneration and renewal. PMID:26987685

  12. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I; Hyngstrom, John R; Garten, Ryan S; Diakos, Nikolaos A; Ives, Stephen J; Dela, Flemming; Larsen, Steen; Drakos, Stavros; Richardson, Russell S

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac, skele...

  13. Technique for producing cardiac radionuclide motion images

    International Nuclear Information System (INIS)

    Sequential frames of different portions of the cardiac cycle are gated into a minicomputer by using an EKG signal recorded onto digital tape simultaneously with imaging information. Serial display of these frames on the computer oscilloscope or projection of 35-mm half frames of these images provides a cardiac motion image with information content adequate for qualitatively assessing cardiac motion. (U.S.)

  14. Regulation of Cardiac Hypertrophy: the nuclear option

    NARCIS (Netherlands)

    D.W.D. Kuster (Diederik)

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, c

  15. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    Science.gov (United States)

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  16. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.

    Science.gov (United States)

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  17. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    Directory of Open Access Journals (Sweden)

    Yali Liu

    2016-01-01

    Full Text Available A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  18. Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2012-02-01

    OBJECTIVE: This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION: Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions.

  19. Response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W; Meine, Mathias M; Doevendans, Pieter A; Pedersen, Susanne S.

    2009-01-01

    Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders...

  20. Rejection in the cardiac transplant

    International Nuclear Information System (INIS)

    Standard chest radiography remains the most frequent applied method for monitoring post surgical cardiac transplant patients. Evidence suggests that after the 1st month cardiac enlargement is indeed a useful indicator of rejection, sometimes being caused by pericardial effusion and/or changes in left ventricular mass. Opportunistic infections, either pulmonary lesions or mediastinal abscesses, as well as malignant tumours may all occur and require evaluation or exclusion. Conventional computed transmission tomography is an excellent technique for surveying the entire thorax relatively non-invasively and is recommended whenever pulmonary, cardiac or mediastinal changes are unexplained. Coronary arteriography with or without digital subtraction remains the definitive method for examining the coronary arteries. Left ventricular function can be evaluated with either angiography or other non-invasive methods including such techniques as echocardiography and nuclear medicine. More recently monoclonal antibody labels for antimyosin show promise for identifying rejection. Ultrafast CT scanning is now available in a number of centres. It allows millisecond cross-sectional cine-tomography of the heart as well as of the whole chest, and also provides 3-D quantitative analyses of end-diastolic and systolic function including regional wall thickening dynamics and estimations of myocardial mass. Right, as well as left-sided cardiac chambers, are demonstrated routinely during the same ultrafast CT procedure. MRI, like ultrafast CT, is a new technique still being explored. MRI as well as MR spectroscopy are regarded as diagnostic radiology procedures. (author). 32 refs.; 3 figs.; 3 tabs

  1. Cardiac functional analysis with MRI

    International Nuclear Information System (INIS)

    Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Even in the 21st century CVD will still be the most frequent cause of morbidity and mortality. Precise evaluation of cardiac function is therefore mandatory for therapy planning and monitoring. In this article the contribution of MRI-based analysis of cardiac function will be addressed. Nowadays cine-MRI is considered as the standard of reference (SOR) in cardiac functional analysis. ECG-triggered steady-state free precession (SSFP) sequences are mainly used as they stand out due to short acquisition times and excellent contrast between the myocardium and the ventricular cavity. An indispensible requirement for cardiac functional analysis is an exact planning of the examination and based on that the coverage of the whole ventricle in short axial slices. By means of dedicated post-processing software, manual or semi-automatic segmentation of the endocardial and epicardial contours is necessary for functional analysis. In this way end-diastolic volume (EDV), end-systolic volume (ESV) and the ejection fraction (EF) are defined and regional wall motion abnormalities (RWMA) can be detected. (orig.)

  2. Molecular therapies for cardiac arrhythmias

    NARCIS (Netherlands)

    G.J.J. Boink

    2013-01-01

    Despite the ongoing advances in pharmacology, devices and surgical approaches to treat heart rhythm disturbances, arrhythmias are still a significant cause of death and morbidity. With the introduction of gene and cell therapy, new avenues have arrived for the local modulation of cardiac disease. Th

  3. The cardiac patient in Ramadan.

    Science.gov (United States)

    Chamsi-Pasha, Majed; Chamsi-Pasha, Hassan

    2016-01-01

    Ramadan is one of the five fundamental pillars of Islam. During this month, the majority of the 1.6 billion Muslims worldwide observe an absolute fast from dawn to sunset without any drink or food. Our review shows that the impact of fasting during Ramadan on patients with stable cardiac disease is minimal and does not lead to any increase in acute events. Most patients with the stable cardiac disease can fast safely. Most of the drug doses and their regimen are easily manageable during this month and may need not to be changed. Ramadan fasting is a healthy nonpharmacological means for improving cardiovascular risk factors. Most of the Muslims, who suffer from chronic diseases, insist on fasting Ramadan despite being exempted by religion. The Holy Quran specifically exempts the sick from fasting. This is particularly relevant if fasting worsens one's illness or delays recovery. Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, decompensated heart failure, recent cardiac intervention or cardiac surgery or any debilitating diseases should avoid fasting. PMID:27144139

  4. Cardiac pacemakers and nuclear batteries

    International Nuclear Information System (INIS)

    Following the introduction giving the indications for cardiac pacemaker therapy with special regard to the use of pacemakers powered by nuclear batteries, reference is made to the resulting radiation exposure of the patient. The activities of the Federal Health Office in this field such as recommendations and surveys including the entire Federal Republic are outlined. (orig.)

  5. CARDIAC TRANSPLANTATION: AN ANESTHETIC CHALLENGE

    OpenAIRE

    Premalatha; Jayaraman,

    2014-01-01

    : Heart transplantation has emerged as the definitive therapy for patients with end-stage cardiomyopathy. The two most common forms of cardiac disease that lead to transplantation are ischemic cardiomyopathy and dilated cardiomyopathy, which together comprise approximately 90% of cases. The other less common forms of heart disease include viral cardiomyopathy, infiltrative cardiomyopathy, postpartum cardiomyopathy, valvular heart disease and congenital heart disease

  6. Epidural analgesia for cardiac surgery

    NARCIS (Netherlands)

    V. Svircevic; M.M. Passier; A.P. Nierich; D. van Dijk; C.J. Kalkman; G.J. van der Heijden

    2013-01-01

    Background A combination of general anaesthesia (GA) with thoracic epidural analgesia (TEA) may have a beneficial effect on clinical outcomes by reducing the risk of perioperative complications after cardiac surgery. Objectives The objective of this review was to determine the impact of perioperativ

  7. Historical highlights in cardiac pacing.

    Science.gov (United States)

    Geddes, L A

    1990-01-01

    The benchmarks in cardiac pacing are identified, beginning with F. Steiner (1871), who rhythmically stimulated the chloroform-arrested hearts of 3 horses, 1 donkey, 10 dogs, 14 cats, and 8 rabbits. The chloroform-arrested heart in human subjects was paced by T. Greene in the following year (1872) in the UK. In 1882, H. Ziemssen in Germany applied cardiac pacing to a 42-year old woman who had a large defect in the anterior left chest wall subsequent to resection of an enchondroma. Intentional cardiac pacing did not occur until 1932, when A.A. Hyman in the US demonstrated that cardiac pacing could be clinically practical. Hyman made a batteryless pacemaker for delivery in induction shock stimuli (60-120/min) to the atria. His pacemaker was powered by a hand-wound, spring-driven generator which provided 6 min of pacemaking without rewinding. Closed-chest ventricular pacing was introduced in the US in 1952 by P.M. Zoll et al. Zoll (1956) also introduced closed-chest ventricular defibrillation. W.L. Weirich et al. (1958) demonstrated that direct-heart stimulation in closed-chest patients could be achieved with slender wire electrodes. S. Furman and J.B. Schwedel (1959) developed a monopolar catheter electrode for ventricular pacing in man. In the same year, W. Greatbatch and W.M. Chardack developed the implantable pacemaker. PMID:18238328

  8. Cardiac arrest: resuscitation and reperfusion.

    Science.gov (United States)

    Patil, Kaustubha D; Halperin, Henry R; Becker, Lance B

    2015-06-01

    The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and

  9. Quantification of 16 QT-prolonging Drugs and Metabolites in Human Postmortem Blood and Cardiac Tissue Using UPLC–MS-MS

    DEFF Research Database (Denmark)

    Mikkelsen, Christian Reuss; Jornil, Jakob; Vukelic Andersen, Ljubica; Banner, Jytte; Hasselstrøm, Jørgen Bo

    2016-01-01

    quantification of 16 QT-prolonging drugs (QTD) and metabolites in postmortem whole blood and postmortem cardiac tissue. Samples were prepared by protein precipitation and quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Deuterated internal standards were used...... blood and cardiac tissue. To the best of the authors’ knowledge, this article presents the first fully validated method for quantification of QTD in cardiac tissue....

  10. The murine cardiac 26S proteasome: an organelle awaiting exploration.

    Science.gov (United States)

    Gomes, Aldrin V; Zong, Chenggong; Edmondson, Ricky D; Berhane, Beniam T; Wang, Guang-Wu; Le, Steven; Young, Glen; Zhang, Jun; Vondriska, Thomas M; Whitelegge, Julian P; Jones, Richard C; Joshua, Irving G; Thyparambil, Sheeno; Pantaleon, Dawn; Qiao, Joe; Loo, Joseph; Ping, Peipei

    2005-06-01

    Multiprotein complexes have been increasingly recognized as essential functional units for a variety of cellular processes, including the protein degradation system. Selective degradation of proteins in eukaryotes is primarily conducted by the ubiquitin proteasome system. The current knowledge base, pertaining to the proteasome complexes in mammalian cells, relies largely upon information gained in the yeast system, where the 26S proteasome is hypothesized to contain a 20S multiprotein core complex and one or two 19S regulatory complexes. To date, the molecular structure of the proteasome system, the proteomic composition of the entire 26S multiprotein complexes, and the specific designated function of individual components within this essential protein degradation system in the heart remain virtually unknown. A functional proteomic approach, employing multidimensional chromatography purification combined with liquid chromatography tandem mass spectrometry and protein chemistry, was utilized to explore the murine cardiac 26S proteasome system. This article presents an overview on the subject of protein degradation in mammalian cells. In addition, this review shares the limited information that has been garnered thus far pertaining to the molecular composition, function, and regulation of this important organelle in the cardiac cells. PMID:16093497

  11. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael;

    2007-01-01

    effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang...

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

    Science.gov (United States)

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

    2016-04-20

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4. PMID:26987380

  13. In Vivo Phosphorylation Site Mapping in Mouse Cardiac Troponin I by High Resolution Top-Down Electron Capture Dissociation Mass Spectrometry: Ser22/23 Are the Only Sites Basally Phosphorylated†

    OpenAIRE

    Ayaz-Guner, Serife; Zhang, Jiang; Li, Lin; Walker, Jeffery W.; Ge, Ying

    2009-01-01

    Cardiac troponin I (cTnI) is the inhibitory subunit of cardiac troponin, a key myofilament regulatory protein complex located on the thin filaments of the contractile apparatus. cTnI is uniquely specific for the heart and is widely used in clinics as a serum biomarker for cardiac injury. Phosphorylation of cTnI plays a critical role in modulating cardiac function. cTnI is known to be regulated by protein kinase A and protein kinase C at five sites, Ser22/Ser23, Ser42/44, and Thr143, primarily...

  14. [Protein-losing enteropathy].

    Science.gov (United States)

    Amiot, A

    2015-07-01

    Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation. PMID:25618488

  15. Optimisation of recombinant production of active human cardiac SERCA2a ATPase

    OpenAIRE

    Antaloae, Ana V.; Cédric Montigny; Marc le Maire; Watson, Kimberly A.; Thomas L-M Sørensen

    2013-01-01

    Methods for recombinant production of eukaryotic membrane proteins, yielding sufficient quantity and quality of protein for structural biology, remain a challenge. We describe here, expression and purification optimisation of the human SERCA2a cardiac isoform of Ca(2+) translocating ATPase, using Saccharomyces cerevisiae as the heterologous expression system of choice. Two different expression vectors were utilised, allowing expression of C-terminal fusion proteins with a biotinylation domain...

  16. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    Science.gov (United States)

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  17. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

  18. Role of cardiac FDG PET-CT in inflammatory cardiomyopathy

    International Nuclear Information System (INIS)

    Full text: Role of cardiac FDG PET-CT in the diagnosis and monitoring treatment response of inflammatory cardiomyopathy. Materials and Methods: This is a retrospective analysis of 72 patients (over a period of 3 years) referred for cardiac PET-CT with dilated cardiomyopathy (DCM) or idiopathic ventricular tachycardia (VT), to rule out inflammatory cardiomyopathy. FDG cardiac PET was done with patients following very high fat low carbohydrate protein preferred diet (VHFLCPPD) protocol one day prior to scan. Myocardial perfusion scan with 99mTc-tetrofosmin or 13N-NH3 was done prior to FDG PET. All patients underwent breathhold CECT, chest PET-CT and cardiac PET-CT 45 min post FDG injection. Scans were reported jointly by a radiologist and nuclear medicine physician. Clinical/pathological follow-up was obtained where possible. Results: 50(69.4%) patients had positive myocardial FDG uptake with matched perfusion defect on NH3/Tc scan in the absence of CAD. 30(42%) patients had associated metabolically active lymphadenopathy and organ lesions. 4 patients had metabolically active lymphnodes with no myocardial inflammation. 18 patients had no abnormality detected on the scan. Patients with positive lymphnodes underwent biopsy and proven to have granulomatous disease either sarcoidosis and with TB or TB alone. 15 patients had post treatment scan which showed complete metabolic response in 7, partial response in 6 and stable disease in 2. Conclusion: Evaluating patients with DCM or idiopathic VT secondary to inflammatory myocarditis is challenging. Cardiac PET scan with VHFLCPPD protocol is the most sensitive modality available for assessment of disease activity in inflammatory cardiomyopathy and monitoring the treatment response especially in patients with ICD

  19. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

    Directory of Open Access Journals (Sweden)

    Esra Cagavi

    Full Text Available As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of

  20. Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

    International Nuclear Information System (INIS)

    Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC

  1. Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H{sub 2}O{sub 2} in HL-1 mouse cardiac muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Rao, F. [Department of Cardiology, Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou (China); Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China); Deng, C.Y. [Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China); Zhang, Q.H.; Xue, Y.M. [Department of Cardiology, Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China); Xiao, D.Z.; Kuang, S.J.; Lin, Q.X.; Shan, Z.X.; Liu, X.Y.; Zhu, J.N. [Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China); Yu, X.Y. [Department of Cardiology, Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou (China); Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China); Wu, S.L. [Department of Cardiology, Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou (China); Guangdong Academy of Medical Sciences, Guangzhou (China)

    2013-09-06

    Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H{sub 2}O{sub 2}), but not angiotensin II, stimulated MIF expression in HL-1 cells. H{sub 2}O{sub 2}-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H{sub 2}O{sub 2}-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

  2. Cardiac Arrest in a Heart Transplant Patient Receiving Dexmedetomidine During Cardiac Catheterization.

    Science.gov (United States)

    Schwartz, Lawrence Israel; Miyamoto, Shelley D; Stenquist, Scott; Twite, Mark David

    2016-06-01

    Dexmedetomidine is an α-2 agonist with a sedative and cardiopulmonary profile that makes it an attractive anesthetic in pediatric cardiac patients. Cardiac transplant patients may suffer from acute cellular rejection of the cardiac conduction system and, therefore, are at an increased risk of the electrophysiological effect of dexmedetomidine. We present such a patient who had a cardiac arrest while receiving dexmedetomidine during cardiac catheterization. Because acute cellular rejection of the cardiac conduction system is difficult to diagnose, dexmedetomidine should be used with caution in pediatric heart transplant patients. PMID:26721807

  3. Resveratrol Upregulates Cardiac SDF-1 in Mice with Acute Myocardial Infarction through the Deacetylation of Cardiac p53.

    Directory of Open Access Journals (Sweden)

    Wang Hong

    Full Text Available We previously demonstrated that resveratrol (RSV administration causes cardiac stromal cell-derived factor (SDF-1 upregulation and can enhance the mobilization of stem cells in mice with acute myocardial infarction (AMI. However, the upstream signal transduction involved in SDF-1 regulation in the setting of AMI and RSV administration remains unclear. Because RSV is a sirtuin 1 (SIRT1 activator and SIRT proteins act as deacetylases, we investigated the role of SIRT1 in SDF-1 upregulation and its subsequent effects.In vitro experiments with H9C2 cardiomyocytes under hypoxia and serum-deprivation conditions showed that p53 acted upstream of SDF-1. RSV could not regulate SDF-1 effectively after SIRT1 silencing, indicating that it is dependent on SIRT1. Subsequently, male C57BL/6 mice were divided into four groups: 1 sham, 2 MI, 3 MI+RSV, and 4 MI+RSV plus nicotinamide, an inhibitor of the deacetylase activity of SIRT (MI+RSV+NAM. Compared with the sham mice, AMI caused a slight increase in the cardiac p53 level and resulted in significant SIRT1 downregulation and p53 acetylation or activation. Compared with the MI mice, MI+RSV administration improved the cardiac SDF-1 level and reversed the reduction of SIRT1 and the activation of p53. Furthermore, we observed less cardiac dysfunction in MI+RSV mice and determined that NAM abolished the effects of RSV.RSV enhances cardiac SDF-1 excretion after AMI partially through a SIRT1 normalization/p53 inactivation pathway.

  4. When did cardiac surgery begin?

    Science.gov (United States)

    Shumacker, H B

    1989-01-01

    Heart surgery is generally regarded as having begun on September 10, 1896 when Ludwig Rehn sutured a myocardial laceration successfully. There are valid reasons, however, to believe that cardiac surgery had its origin nearly a century earlier with the operative drainage of the pericardium by the little known Spanish surgeon, Francisco Romero, and highly regarded Baron Dominique Jean Larrey. This procedure entailed making a thoracic incision and opening and draining the pericardium. It must necessarily be considered a cardiac operation. The pericardium is part of the heart; its epicardium continues as the serosal layer of the fibrous pericardium; the pericardium is fused to the heart's base and great vessels; all books on heart surgery include pericardial operations. When Romero first operated is unknown, but it antedated 1814 when his work was presented in Paris; Larrey's operation was performed in 1810. These contributions are presented, and their priority with regard to the later initial efforts to suture myocardial laceration is reviewed briefly. PMID:2651455

  5. Historical perspectives of cardiac electrophysiology.

    Science.gov (United States)

    Lüderitz, Berndt

    2009-01-01

    The diagnosis and treatment of clinical electrophysiology has a long and fascinating history. From earliest times, no clinical symptom impressed the patient (and the physician) more than an irregular heart beat. Although ancient Chinese pulse theory laid the foundation for the study of arrhythmias and clinical electrophysiology in the 5th century BC, the most significant breakthrough in the identification and treatment of cardiac arrhythmias first occurred in this century. In the last decades, our knowledge of electrophysiology and pharmacology has increased exponentially. The enormous clinical significance of cardiac rhythm disturbances has favored these advances. On the one hand, patients live longer and thus are more likely to experience arrhythmias. On the other hand, circulatory problems of the cardiac vessels have increased enormously, and this has been identified as the primary cause of cardiac rhythm disorders. Coronary heart disease has become not just the most significant disease of all, based on the statistics for cause of death. Arrhythmias are the main complication of ischemic heart disease, and they have been directly linked to the frequently arrhythmogenic sudden death syndrome, which is now presumed to be an avoidable "electrical accident" of the heart. A retrospective look--often charming in its own right--may not only make it easier to sort through the copious details of this field and so become oriented in this universe of important and less important facts: it may also provide the observer with a chronological vantage point from which to view the subject. The study of clinical electrophysiology is no dry compendium of facts and figures, but rather a dynamic field of study evolving out of the competition between various ideas, intentions and theories. PMID:19196616

  6. Cardiac rehabilitation: a comprehensive review

    OpenAIRE

    Lear Scott A; Ignaszewski Andrew

    2001-01-01

    Abstract Cardiac rehabilitation (CR) is a commonly used treatment for men and women with cardiovascular disease. To date, no single study has conclusively demonstrated a comprehensive benefit of CR. Numerous individual studies, however, have demonstrated beneficial effects such as improved risk-factor profile, slower disease progression, decreased morbidity, and decreased mortality. This paper will review the evidence for the use of CR and discuss the implications and limitations of these stu...

  7. Cardiac Biomarkers in Hyperthyroid Cats

    OpenAIRE

    Sangster, J.K.; Panciera, D L; Abbott, J.A.; Zimmerman, K.C.; Lantis, A.C.

    2013-01-01

    Background Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT‐proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been extensively investigated in hyperthyroidism. Hypothesis Plasma NT‐proBNP and cTNI concentrations are higher in cats with primary myocardial disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats. Animals Twenty‐three hyperthyro...

  8. Functiogenesis of cardiac pacemaker activity.

    Science.gov (United States)

    Sakai, Tetsuro; Kamino, Kohtaro

    2016-07-01

    Throughout our investigations on the ontogenesis of the electrophysiological events in early embryonic chick hearts, using optical techniques to record membrane potential probed with voltage-sensitive dyes, we have introduced a novel concept of "functiogenesis" corresponding to "morphogenesis". This article gives an account of the framework of "functiogenesis", focusing on the cardiac pacemaker function and the functional organization of the pacemaking area. PMID:26719289

  9. Comparative Aspects of Cardiac Adaptation

    Czech Academy of Sciences Publication Activity Database

    Ošťádal, Bohuslav

    New York : Springer, 2013 - (Ošťádal, B.; Dhalla, N.), s. 3-18 ISBN 978-1-4614-5202-7. - (Advances in Biochemistry in Health and Disease) R&D Projects: GA ČR(CZ) GAP302/11/1308 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : cardiac adaptation * poikilotherms * homeotherms Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  10. Cardiac Biomarkers and Cycling Race

    OpenAIRE

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-01-01

    In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011), but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac bi...

  11. Cardiac involvement in tuberous sclerosis.

    OpenAIRE

    Mühler, E G; Turniski-Harder, V; Engelhardt, W.; von Bernuth, G

    1994-01-01

    OBJECTIVE--To assess the incidence, importance, and history of cardiac involvement in infants and children with tuberous sclerosis. DESIGN--Prospective study; clinical examination, sector and Doppler echocardiography, standard and ambulatory electrocardiography. SETTING--A tertiary referral centre. PATIENTS--21 patients with tuberous sclerosis aged 1 day to 16 years (mean 6.3 years); follow up investigations were available in 14 cases (10 retrospective, 4 prospective; mean follow up 4.3 years...

  12. Cardiac MRI in restrictive cardiomyopathy

    International Nuclear Information System (INIS)

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  13. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  14. Gastrointestinal complications and cardiac surgery.

    Science.gov (United States)

    Allen, Sara J

    2014-06-01

    Gastrointestinal (GI) complications are an uncommon but potentially devastating complication of cardiac surgery. The reported incidence varies between .3% and 5.5% with an associated mortality of .3-87%. A wide range of GI complications are reported with bleeding, mesenteric ischemia, pancreatitis, cholecystitis, and ileus the most common. Ischemia is thought to be the main cause of GI complications with hypoperfusion during cardiac surgery as well as systemic inflammation, hypothermia, drug therapy, and mechanical factors contributing. Several nonischemic mechanisms may contribute to GI complications, including bacterial translocation, adverse drug reactions, and iatrogenic organ injury. Risk factors for GI complications are advanced age (>70 years), reoperation or emergency surgery, comorbidities (renal disease, respiratory disease, peripheral vascular disease, diabetes mellitus, cardiac failure), perioperative use of an intra-aortic balloon pump or inotrope therapy, prolonged surgery or cardiopulmonary bypass, and postoperative complications. Multiple strategies to reduce the incidence of GI complications exist, including risk stratification scores, targeted inotrope and fluid therapy, drug therapies, and modification of cardiopulmonary bypass. Currently, no single therapy has consistently proven efficacy in reducing GI complications. Timely diagnosis and treatment, while tailored to the specific complication and patient, is essential for optimal management and outcomes in this challenging patient population. PMID:25208431

  15. Possible Protective Role of Carnosine against gamma-Radiation-Induced Cardiac Dysfunction in Mice

    International Nuclear Information System (INIS)

    Oxidative Stress with subsequent production of reactive oxygen species (ROS) has been postulated as one of the mechanisms of cardiac toxicity. Carnosine (β-alanyl-L-histidine) a biological antioxidant, is a relatively non-toxic dipeptide which possesses many functions (antiglycator, scavenger of ions of zinc and copper, toxic aldehydes and protein carbonyls) that are likely to suppress oxidative stress. The aim of the present work is to investigate the possible protective effects of carnosine on gamma-radiation-induced cardiac damage in mice. Carnosine was supplemented daily to mice (50 mg/ Kg body wt), by gavage, 10 days before whole body gamma-irradiation at a dose of 5 Gy (applied as a shot dose). The results obtained showed that whole body gamma-irradiation of mice produced biochemical alteration in levels of serum glucose and lipid profile fractions. Furthermore, some markers of cardiac injury enzymes as serum lactate dehydrogenase (LDH), creatin phosphokinase (CPK) and aspartate transaminase (AST) activities showed significant increases associated with alteration in the antioxidant status of cardiac tissues. Significant increases of lipid peroxidation end product malonaldehyde (MDA) and protein carbonyl levels, xanthine oxidase (XO) activity along with reduction in the activity of cardiac antioxidant enzymes; glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were observed. Carnosine-treatment prior irradiation has attenuated the cardiotoxic effects of radiation obvious by reduction in the levels of MDA and protein carbonyl and XO activity, rescued the depletion of endogenous antioxidant enzymes and diminished the increases of cardiac injury markers. It could be postulated that carnosine as a multi-functional dietary supplement could exert a modulator role in the radiation-induced cardiac damage and serum biochemical changes through its antioxidant properties

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-28

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

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

    International Nuclear Information System (INIS)

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca2+ signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7−/−) and wild-type mice (anxa7+/+) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7−/− mice than in anxa7+/+ mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions

  18. Downregulation of Rho associated coiled-coil forming protein kinase 1 in the process of delayed myocardialization of cardiac proximal outflow tract septum in connexin 43 knockout mice embryo

    Institute of Scientific and Technical Information of China (English)

    QI Chun-hua; ZHAO Xiao-qing; MA Duan; MA Xiao-jing; ZHOU Guo-min; HUANG Guo-ying

    2011-01-01

    Background The connexln43 knockout (Cx43 KO) mouse dies at birth with an enlarged conotruncal region, which leads to the obstruction of the right outflow tract (OFT). Since myocardialization of the proximal OFT septum is one of the key events during heart development, we investigated the process in the Cx43 KO embryo hearts. Rho associated coiled-coil forming protein kinase 1 (ROCK1), is a recently found key molecule to regulate the myocardialization of OFT, but its spatiotemporal expression pattern during myocardialization remains unknown. The objective of this study was to investigate the differentially expressed pattern of ROCK1 between Cx43 KO and wild type embryo hearts, and its relationship with the delayed myocardialization in Cx43 KO embryo hearts.Methods Using immunohistochemistry, the processes of myocardiolization were investigated both in Cx43 KO and wild type embryo hearts. The differentially expressed pattern of ROCK1 between Cx43 KO and wildtype embryo hearts was evaluated both at the mRNA and protein level by real-time RT-PCR and immunohistochemistry.Results The expression of α-sarcomeric actin (α-SCA) in the proximal OFT septum of Cx43 KO embryos was delayed. Meanwhile, it was shown that the downregulation of ROCK1 coincided with delayed myocardialization. The expression of ROCK1 protein was mainly limited to the proximal outflow tract septum from embryo day (E) E11.5 to E15.5. Its expression pattern was similar with that of α-SCA. Real-time RT-PCR found that the expression level of Rock-1 mRNA began at a low level on E11.5 and reached peak at E13.5 and E14.5.Conclusions ROCK1 may have an important role in the process of myocardialization of the proximal OFT septum. Downregulation of ROCK1 is likely to contribute to the aberrant myocardialization in Cx43 KO embryo hearts.

  19. Identifying potential functional impact of mutations and polymorphisms: Linking heart failure, increased risk of arrhythmias and sudden cardiac death.

    Directory of Open Access Journals (Sweden)

    BENOIT eJAGU

    2013-09-01

    Full Text Available Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behaviour has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis and the degradation of ion channel α-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking.

  20. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction.

    Science.gov (United States)

    Bers, Donald M

    2014-01-01

    Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease. PMID:24245942

  1. Cardiac tamponade: contrast reflux as an indicator of cardiac chamber equalization

    Directory of Open Access Journals (Sweden)

    Nauta Foeke Jacob

    2012-05-01

    Full Text Available Abstract Background Traumatic hemopericardium remains a rare entity; it does however commonly cause cardiac tamponade which remains a major cause of death in traumatic blunt cardiac injury. Objectives We present a case of blunt chest trauma complicated by cardiac tamponade causing cardiac chamber equalization revealed by reflux of contrast. Case report A 29-year-old unidentified male suffered blunt chest trauma in a motor vehicle collision. Computed tomography (CT demonstrated a periaortic hematoma and hemopericardium. Significant contrast reflux was seen in the inferior vena cava and hepatic veins suggesting a change in cardiac chamber pressures. After intensive treatment including cardiac massage this patient expired of cardiac arrest. Conclusion Reflux of contrast on CT imaging can be an indicator of traumatic cardiac tamponade.

  2. B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study

    Directory of Open Access Journals (Sweden)

    Staines Harry

    2008-11-01

    Full Text Available Abstract Background Few studies have addressed whether the combined use of B-type natriuretic peptide (BNP and high-sensitive C-reactive protein (hsCRP improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS. Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT positive cardiac events in 871 patients admitted to the emergency department. Methods Blood samples were obtained immediately following admission. Results After a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145–736 versus 75 (29–235 pq/mL [median, 25 and 75% percentiles], p = 0.000. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR for BNP in the highest quartile (Q4 was 5.13 (95% confidence interval (CI, 1.97–13.38 compared to the lowest quartile (Q1 and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89–115.63 compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission. Conclusion BNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification

  3. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias.

    Science.gov (United States)

    Chopra, Nagesh; Yang, Tao; Asghari, Parisa; Moore, Edwin D; Huke, Sabine; Akin, Brandy; Cattolica, Robert A; Perez, Claudio F; Hlaing, Thinn; Knollmann-Ritschel, Barbara E C; Jones, Larry R; Pessah, Isaac N; Allen, Paul D; Franzini-Armstrong, Clara; Knollmann, Björn C

    2009-05-01

    Heart muscle excitation-contraction (E-C) coupling is governed by Ca(2+) release units (CRUs) whereby Ca(2+) influx via L-type Ca(2+) channels (Cav1.2) triggers Ca(2+) release from juxtaposed Ca(2+) release channels (RyR2) located in junctional sarcoplasmic reticulum (jSR). Although studies suggest that the jSR protein triadin anchors cardiac calsequestrin (Casq2) to RyR2, its contribution to E-C coupling remains unclear. Here, we identify the role of triadin using mice with ablation of the Trdn gene (Trdn(-/-)). The structure and protein composition of the cardiac CRU is significantly altered in Trdn(-/-) hearts. jSR proteins (RyR2, Casq2, junctin, and junctophilin 1 and 2) are significantly reduced in Trdn(-/-) hearts, whereas Cav1.2 and SERCA2a remain unchanged. Electron microscopy shows fragmentation and an overall 50% reduction in the contacts between jSR and T-tubules. Immunolabeling experiments show reduced colocalization of Cav1.2 with RyR2 and substantial Casq2 labeling outside of the jSR in Trdn(-/-) myocytes. CRU function is impaired in Trdn(-/-) myocytes, with reduced SR Ca(2+) release and impaired negative feedback of SR Ca(2+) release on Cav1.2 Ca(2+) currents (I(Ca)). Uninhibited Ca(2+) influx via I(Ca) likely contributes to Ca(2+) overload and results in spontaneous SR Ca(2+) releases upon beta-adrenergic receptor stimulation with isoproterenol in Trdn(-/-) myocytes, and ventricular arrhythmias in Trdn(-/-) mice. We conclude that triadin is critically important for maintaining the structural and functional integrity of the cardiac CRU; triadin loss and the resulting alterations in CRU structure and protein composition impairs E-C coupling and renders hearts susceptible to ventricular arrhythmias. PMID:19383796

  4. Cardiac Stem Cells: Biology and Clinical Applications

    OpenAIRE

    Goichberg, Polina; Chang, Jerway; Liao, Ronglih; Leri, Annarosa

    2014-01-01

    Significance: Heart disease is the primary cause of death in the industrialized world. Cardiac failure is dictated by an uncompensated reduction in the number of viable and fully functional cardiomyocytes. While current pharmacological therapies alleviate the symptoms associated with cardiac deterioration, heart transplantation remains the only therapy for advanced heart failure. Therefore, there is a pressing need for novel therapeutic modalities. Cell-based therapies involving cardiac stem ...

  5. Cardiac imaging: Current and emerging applications

    OpenAIRE

    Jankharia B; Raut A

    2010-01-01

    Cardiac magnetic resonance imaging (MRI) and computed tomography (CT) scan have made big inroads as modalities used for evaluation of various pathologies of the heart. Cardiac MRI is typically used for perfusion and viability studies as well as to study various cardiomyopathies, valvular diseases and the pericardium. It has been used in the evaluation of congenital heart diseases over the last two decades. Cardiac CT is used mainly for the evaluation of the coronary arteries, typically in the...

  6. Disseminated cysticercosis with pulmonary and cardiac involvement

    OpenAIRE

    Jain Bharat; Sankhe Shilpa; Agrawal Mukta; Naphade Prashant

    2010-01-01

    Pulmonary and cardiac involvement by cysticercosis is extremely rare, and is usually asymptomatic. We report the case of a 19-year-old boy who presented with a history of headache and vomiting and was found to have disseminated cysticercosis with pulmonary and cardiac involvement; the emphasis is on the rare occurrence of pulmonary, cardiac, pancreatic, intraocular, and extradural spinal canal involvement in the same patient. This case demonstrates the extent to which cysticercosis can be dis...

  7. Motivational factors of adherence to cardiac rehabilitation

    OpenAIRE

    Shahsavari, Hooman; Shahriari, Mohsen; Alimohammadi, Nasrollah

    2012-01-01

    Background: Main suggested theories about patients’ adherence to treatment regimens recognize the importance of motivation in positive changes in behaviors. Since cardiac diseases are chronic and common, cardiac rehabilitation as an effective prevention program is crucial in management of these diseases. There is always concern about the patients’ adherence to cardiac rehabilitation. The aim of this study was to describe the motivational factors affecting the patients’ participation and compl...

  8. Cardiac tumours simulating collagen vascular disease.

    OpenAIRE

    Fitzpatrick, A. P.; Lanham, J. G.; Doyle, D V

    1986-01-01

    Cardiac tumours can mimic collagen vascular disease and they are often accompanied by profound systemic upset. Both benign and malignant tumours may present in this way. Three cases of cardiac tumour, two malignant and one benign, are reported with just such a presentation. A review of fifteen similar case reports showed that a spectrum of different collagen vascular diseases was diagnosed and treated before the true diagnosis emerged. In half of these cases the cardiac tumour was only diagno...

  9. Methods in pharmacology: measurement of cardiac output

    OpenAIRE

    Geerts, Bart F; Aarts, Leon P; Jansen, Jos R.

    2011-01-01

    Many methods of cardiac output measurement have been developed, but the number of methods useful for human pharmacological studies is limited. The ‘holy grail’ for the measurement of cardiac output would be a method that is accurate, precise, operator independent, fast responding, non-invasive, continuous, easy to use, cheap and safe. This method does not exist today. In this review on cardiac output methods used in pharmacology, the Fick principle, indicator dilution techniques, arterial pul...

  10. Electrocardiographically Determination of Cardiac Enlargements in Dogs

    OpenAIRE

    Gönül, Remzi; OR, Mehmet Erman; DODURKA, Tamer

    2002-01-01

    In this study, the electrocardiographic parameters necessary to determine cardiac enlargements and to establish and distinguish such complaints from each other in the early stage in dogs with circulatory problems were assessed. The material of the study consisted of 33 dogs 1.5-15 years of age with cardiac enlargements determined from 140 dogs suspected of having cardiac disease based on clinical, radiographic and electrocardiographic analyses. In these dogs, 12 cases of left atrial hypert...

  11. Interdisciplinary preoperative patient education in cardiac surgery.

    OpenAIRE

    De Weert, J.; van Dulmen, S.; Bar, P.; Venus, E.

    2003-01-01

    Patient education in cardiac surgery is complicated by the fact that cardiac surgery patients meet a lot of different health care providers. Little is known about education processes in terms of interdisciplinary tuning. In this study, complete series of consecutive preoperative consultations of 51 cardiac surgery patients with different health care providers (physicians, nurses and health educators) were videotaped. The information exchange between patients and providers was analyzed directl...

  12. Digital subtraction angiography in cardiac diseases

    International Nuclear Information System (INIS)

    DSA was done in 133 examinations of 128 patients during 2 years consist of 9 examination of IV DSA and 124 examination of selective cardiac DSA after cardiac catheterization. Open heart surgery was performed in 90 patients and 12 patients showed discrepancy between pre-and post operative diagnosis, showing a total 86.7% of diagnostic accuracy with DSA. We experienced the significant reduction in dose of contrast media, 30-40% of dose of conventional cardiac angiography. It is concluded that DSA is useful in the evaluation of septal defects, valvular disease and other congenital heart disease. DSA is an accurate simple and safe method in evaluating of cardiac diseases.

  13. Contemporary Breast Radiotherapy and Cardiac Toxicity.

    Science.gov (United States)

    Yeboa, Debra Nana; Evans, Suzanne Buckley

    2016-01-01

    Long-term cardiac effects are an important component of survivorship after breast radiotherapy. The pathophysiology of cardiotoxicity, history of breast radiotherapy, current methods of cardiac avoidance, modern outcomes, context of historical outcomes, quantifying cardiac effects, and future directions are reviewed in this article. Radiation-induced oxidative stress induces proinflammatory cytokines and is a process that potentiates late effects of fibrosis and intimal proliferation in endothelial vasculature. Breast radiation therapy has changed substantially in recent decades. Several modern technologies exist to improve cardiac avoidance such as deep inspiration breath hold, gating, accelerated partial breast irradiation, and use of modern 3-dimensional planning. Modern outcomes may vary notably from historical long-term cardiac outcomes given the differences in cardiac dose with modern techniques. Methods of quantifying radiation-related cardiotoxicity that correlate with future cardiac risks are needed with current data exploring techniques such as measuring computed tomography coronary artery calcium score, single-photon emission computed tomography imaging, and biomarkers. Placing historical data, dosimetric correlations, and relative cardiac risk in context are key when weighing the benefits of radiotherapy in breast cancer control and survival. Estimating present day cardiac risk in the modern treatment era includes challenges in length of follow-up and the use of confounding cardiotoxic agents such as evolving systemic chemotherapy and targeted therapies. Future directions in both multidisciplinary management and advancing technology in radiation oncology may provide further improvements in patient risk reduction and breast cancer survivorship. PMID:26617212

  14. MRI in cardiac sarcoidosis and amyloidosis

    International Nuclear Information System (INIS)

    Sarcoidosis and amyloidosis are both multisystem disorders, which may involve the heart; however, isolated cardiac disease is rare. Diagnosis of cardiac sarcoidosis and amyloidosis is crucial because the patient prognosis is dependent on cardiac involvement and early treatment. Echocardiography is the first line imaging modality in the diagnostic work-up of both diseases, possibly giving hints towards the correct diagnosis. Besides myocardial biopsy and radionuclide studies cardiac magnetic resonance imaging (MRI) is routinely performed in patients suspect of having infiltrative cardiomyopathy. The T1 mapping procedure is currently being evaluated as a new technique for detection and quantification of global myocardial enhancement, as seen in cardiac amyloidosis. Sensitivities and specificities for detection of cardiac sarcoidosis and amyloidosis can be significantly improved by MRI, especially with late gadolinium enhancement (LGE) imaging. In cardiac sarcoidosis the use of LGE is outcome-related while in amyloidosis analysis of T1-mapping may be of prognostic value. If cardiac involvement in sarcoidosis or amyloidosis is suspected cardiac MRI including LGE should be performed for establishing the diagnosis. (orig.)

  15. [Out-of-hospital cardiac arrest].

    Science.gov (United States)

    Virkkunen, Ilkka; Hoppu, Sanna; Kämäräinen, Antti

    2011-01-01

    Cardiac arrest as the first symptom of coronary artery disease is not uncommon. Some of previously healthy people with sudden cardiac arrest may be saved by effective resuscitation and post-resuscitative therapy. The majority of cardiac arrest patients experience the cardiac arrest outside of the hospital, in which case early recognition of lifelessness, commencement of basic life support and entry to professional care without delay are the prerequisites for recovery. After the heart has started beating again, the clinical picture of post-resuscitation syndrome must be recognized and appropriate treatment utilized. PMID:22204143

  16. Cardiac tissue engineering in magnetically actuated scaffolds

    International Nuclear Information System (INIS)

    Cardiac tissue engineering offers new possibilities for the functional and structural restoration of damaged or lost heart tissue by applying cardiac patches created in vitro. Engineering such functional cardiac patches is a complex mission, involving material design on the nano- and microscale as well as the application of biological cues and stimulation patterns to promote cell survival and organization into a functional cardiac tissue. Herein, we present a novel strategy for creating a functional cardiac patch by combining the use of a macroporous alginate scaffold impregnated with magnetically responsive nanoparticles (MNPs) and the application of external magnetic stimulation. Neonatal rat cardiac cells seeded within the magnetically responsive scaffolds and stimulated by an alternating magnetic field of 5 Hz developed into matured myocardial tissue characterized by anisotropically organized striated cardiac fibers, which preserved its features for longer times than non-stimulated constructs. A greater activation of AKT phosphorylation in cardiac cell constructs after applying a short-term (20 min) external magnetic field indicated the efficacy of magnetic stimulation to actuate at a distance and provided a possible mechanism for its action. Our results point to a synergistic effect of magnetic field stimulation together with nanoparticulate features of the scaffold surface as providing the regenerating environment for cardiac cells driving their organization into functionally mature tissue. (paper)

  17. A comparison of genetic findings in sudden cardiac death victims and cardiac patients

    DEFF Research Database (Denmark)

    Hertz, Christin L; Ferrero-Miliani, Laura; Frank-Hansen, Rune;

    2015-01-01

    Sudden cardiac death (SCD) is responsible for a large proportion of non-traumatic, sudden and unexpected deaths in young individuals. Sudden cardiac death is a known manifestation of several inherited cardiac diseases. In post-mortem examinations, about two-thirds of the SCD cases show structural...

  18. [Thoracic lavage and open cardiac massage as treatment of hypothermic cardiac arrest--case report].

    Science.gov (United States)

    Koponen, Timo; Vänni, Ville; Kettunen, Minna; Reinikainen, Matti; Hakala, Tapio

    2016-01-01

    Cardiopulmonary bypass is the treatment of choice for a severely hypothermic patient with cardiac arrest. However, the treatment is not always available. We describe a successful three-and-a-half hour resuscitation of a hypothermic cardiac arrest patient with manual chest compressions followed by open cardiac massage and rewarming with thoracic lavage. PMID:27188092

  19. G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart

    OpenAIRE

    Pang, Jinjiang; Xu, Xiangbin; Getman, Michael R.; Shi, Xi; Belmonte, Stephen L.; Michaloski, Heidi; Mohan, Amy; Blaxall, Burns C.; Berk, Bradford C.

    2011-01-01

    G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multi-function scaffold protein. However, little is known about its physiological role in the heart. Here we sought to identify the cardiac function of GIT1. Global GIT1 knockout (KO) mice were generated and exhibited significant cardiac hypertrophy that progressed to heart failure. Electron microscopy revealed that the hearts of GIT1 KO mice demonstrated significant morphological abnormities in mitochondria, including...

  20. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis

    Science.gov (United States)

    Tse, Gary; Yan, Bryan P.; Chan, Yin W. F.; Tian, Xiao Yu; Huang, Yu

    2016-01-01

    Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodeling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure. PMID:27536244

  1. Imaging features of cardiac myxoma

    International Nuclear Information System (INIS)

    Objective: To study the imaging features of cardiac myxoma and their diagnostic values. Methods: Twenty-two patrents with cardiac myxoma were reviewed retrospectively for the clinical, pathologic, and radiologic findings. Posteroanterior and lateral chest radiographs, American Imatron C-150 XP Electron Beam CT examination, and Germany Siemens 1.5T Magnetom Vision MR scan were performed on every patient. Results: (1) Radiographs of 17 patients with left atrial myxoma showed evidence of mitral valve obstruction in 14(82.3%), radiographs of 5 patients with right atrial myxoma demonstrated right atrium enlargement in 3(60%) respectively. (2) CT scans of 22 myxomas demonstrated 18 (81.8%) lesions were hypoattenuated and 4 (19.1%) were isoattenuated relative to the myocardium. Calcification or ossification was seen in 3 patients. All myxomas apart from massive one were found attaching to the atrial septum. Movie mode could dis- play the movement of myxoma across the atrioventicular valves. (3) MRI studies of 22 myxomas showed 19 (86.3%) heterogeneous signal intensity and 3 (13.7%) homogeneous. They exhibited slight high or homogeneous signal intensity with both T1- and T2-weighted sequences, and low signal intensity with cine gradient recalled echo sequences. Point of attachment was visible in 21 (95.4%) cases. Conclusion: The typical radiograph sign of cardiac myxomas is mitral valve obstruction, CT and MR can demonstrate intracavitary lobular masses attacthing to artrial spetum. The latter two kinds of examinations not only provide accurate assessment of the size, location, and attachment point of these lesions, but also have important qualitative diagnostic advantage. (authors)

  2. EVALUATION OF NEONATAL CARDIAC MURMURS

    Directory of Open Access Journals (Sweden)

    Somaiah

    2014-09-01

    Full Text Available Cardiovascular malformations are the most common cause of congenital malformations, the diagnosis of which requires a close observation in the neonatal period. Early recognition of CHD is important in the neonatal period, as many of them may be fatal if undiagnosed and may require immediate intervention. The objectives of this study are to study the epidemiology of neonatal cardiac murmurs, to identify clinical characteristics which differentiate pathological murmur from functional murmurs and to assess the reliability of clinical evaluation in diagnosing CHD. Method of study included all neonates admitted to the NICU, postnatal ward, attending pediatric OPD or neonatal follow up clinic and were detected to have cardiac murmurs. It was a cross sectional study over a period of 16months. A clinical diagnosis was made based on history and clinical examination. Then Chest X-ray and ECG, Echocardiography was done in all neonates for confirmation of the diagnosis. These neonates were again examined daily till they were in hospital and during the follow-up visit at 6 weeks. The results of 70 neonates in this study conducted over a period of 24 months included the incidence of cardiac murmurs among intramural neonates which was 13.5 for 1000 live births. Most frequent symptom was fast breathing in 10(14.3% cases. VSD was the most common diagnosis clinically in 23 (33% babies. The most frequent Echo diagnosis was acyanotic complex congenital heart disease in 25(36% cases followed by 12(17% cases each of VSD and ASD respectively. Overall in our study 77.1% (54cases of the murmurs were diagnosed correctly and confirmed by Echocardiography The study concluded that it is possible to make clinical diagnosis in many cases of congenital heart diseases, the functional murmurs could be differentiated from those arising from structural heart disease and evaluation of the infants based only on murmurs, few congenital heart diseases can be missed.

  3. Sudden Cardiac Death and Post Cardiac Arrest Syndrome. An Overview

    Directory of Open Access Journals (Sweden)

    Zima Endre

    2015-10-01

    Full Text Available A satisfactory neurologic outcome is the key factor for survival in patients with sudden cardiac death (SCD, however this is highly dependent on the haemodynamic status. Short term cardiopulmonary resuscitation and regained consciousness on the return of spontaneous circulation (ROSC is indicative of a better prognosis. The evaluation and treatment of SCD triggering factors and of underlying acute and chronic diseases will facilitate prevention and lower the risk of cardiac arrest. Long term CPR and a prolonged unconscious status after ROSC, in the Intensive Care Units or Coronary Care Units, indicates the need for specific treatment and supportive therapy including efforts to prevent hyperthermia. The prognosis of these patients is unpredictable within the first seventy two hours, due to unknown responses to therapeutic management and the lack of specific prognostic factors. Patients in these circumstances require the highest level of intensive care and aetiology driven treatment without any delay, independently of their coma state. Current guidelines sugest the use of multiple procedures in arriving at a diagnosis and prognosis of these critical cases.

  4. Adiponectin Ameliorates Endotoxin-Induced Acute Cardiac Injury

    Directory of Open Access Journals (Sweden)

    Yoshio Watanabe

    2014-01-01

    Full Text Available Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS- induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10 mg/kg was intraperitoneally injected into wild-type (WT and adiponectin-knockout (APN-KO mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF-α and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF-α and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction.

  5. Cardiac remodeling and physical training post myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Michael; A; Garza; Emily; A; Wason; John; Q; Zhang

    2015-01-01

    After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.

  6. Biologically improved nanofibrous scaffolds for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

  7. Biologically improved nanofibrous scaffolds for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Bhaarathy, V. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Lee Kong Chian School of Medicine, Nanyang Technological University, 138673 (Singapore); Venugopal, J., E-mail: nnijrv@nus.edu.sg [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Gandhimathi, C. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Ponpandian, N.; Mangalaraj, D. [Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Ramakrishna, S. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore)

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

  8. Introduction to noninvasive cardiac mapping.

    Science.gov (United States)

    Bear, Laura; Cuculich, Phillip S; Bernus, Olivier; Efimov, Igor; Dubois, Rémi

    2015-03-01

    From the dawn of the twentieth century, the electrocardiogram (ECG) has revolutionized the way clinical cardiology has been practiced, and it has become the cornerstone of modern medicine today. Driven by clinical and research needs for a more precise understanding of cardiac electrophysiology beyond traditional ECG, inverse solution electrocardiography has been developed, tested, and validated. This article outlines the important progress from ECG development, through more extensive measurement of body surface potentials, and the fundamental leap to solving the inverse problem of electrocardiography, with a focus on mathematical methods and experimental validation. PMID:25784020

  9. Autologous Transfusion in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Radmehr H

    2003-11-01

    Full Text Available Preoperative autologous blood donation is commonly used to reduce exposure to homologous blood transfusions among patients undergoing elective cardiac surgery. The aim of this study was to evaluate the effect of autologous transfusion on patients' hematocryte value, intra and postoperative blood loss, hospitalization time, the development of infective complications and other factors. Materials and Methods: Between June 2001 to April 2002, 208 patients were underwent cardiac surgery in cardiac surgery ward in Imam Khomeini Medical Center. One or more blood units donate from 104 Patients before cardiopulmonary bypass and heparin injection, and transfused to them after CPB and Protamin injection (autologous Group, group 1. 104 patients underwent cardiac surgery routinely (control group, group 2."nResults: Mean of age was 55.9±8.6 in group 1 and 56.6±9.3 in group 2 (P=NS. 73 male and 31 females were in group 1 and 79 males and 25 females were in group 2 (P=NS. Smoking, familial history, hyperlipidemia, diabetes mellitus, renal failure, hypertension, stroke, and history of myocardial infarction was similar in two groups."nSeverity of angina, urgency operation, number vessels disease, duration of cardiopulmonary bypass, duration of aortic cross clamp time, use of internal thoracic artery graft, and number of grafts was similar in both groups. Mean of bleeding post operation was 548 cc in group 1 and 803 cc in-group 2 (P=0.003. Bleeding that need to operation was 1.8% in group 1 and 8.6% in group 2 (P=0.002. Wound infection, mediastinitis, renal failure, ventilatory prolonged, stroke, need to Intra-aortic Balloon Pump (IABP, intraoperative bleeding, and hospital stay was similar in both groups. Mean of extubationt time was 10.2 hours in group 1 and 14.8 hours in group 2 (P=0.001."nConclusion: Preoperative and intra-operative donations are safe and continue to contribute uniquely to blood conservation, providing important options in comprehensive

  10. [Acute cardiac failure in pheochromocytoma.

    DEFF Research Database (Denmark)

    Jønler, Morten; Munk, Kim

    2008-01-01

    Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...... in left ventricular function and elevated myocardial enzymes. No coronary stenoses were found. The myocardium regained nearly normal systolic function in one and a half month. A renal P was laparoscopicaly removed. We discuss the pathophysiology of catecholamine cardiomyopathy. Udgivelsesdato: 2008...

  11. Cardiac leiomyosarcoma, a case report

    DEFF Research Database (Denmark)

    Andersen, Rikke; Kristensen, Bjarne W; Gill, Sabine

    2013-01-01

    In this case report we present the history of a patient admitted with recurrent pulmonary edema. Transesophageal chocardiography showed a tumour in the left atrium, occluding the ostium of the mitral valve and mimicking intermittent mitral stenosis. Cardiac surgery followed by pathological...... examination revealed that the tumour was a leiomyosarcoma. Images from the echocardiography as well as the pathological findings are shown and discussed. The present case report illustrates that atrial tumors comprise also sarcomas, suggesting the use of careful, rapid diagnostic procedures and treatment to...

  12. MR-guided cardiac catheterization

    International Nuclear Information System (INIS)

    Exposing young children to X-rays is a source of concern, since the effect is cumulative and it is important to avoid adding to their lifetime dose. This becomes particularly significant in the case of congenital heart disease, as the patients often need life-long monitoring and successive interventions. Alternative imaging techniques are needed in order to eliminate or limit X-ray exposure. This article demonstrates the feasibility of MR-guided cardiac catheterization using passive device visualization. The procedures are performed in a Philips XMR suite, where all or a substantial part of the catheterization procedure is performed with MR guidance, resulting in significant dose savings. (orig.)

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

    Science.gov (United States)

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

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats. PMID:24905340

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with...

  15. Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

    DEFF Research Database (Denmark)

    Müller, Hanna; Renner, Marcus; Bergmann, Frank;

    2013-01-01

    Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense compo...

  16. Assessment of cardiac sympathetic nerve integrity with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Raffel, David M. E-mail: raffel@umich.edu; Wieland, Donald M

    2001-07-01

    The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation.

  17. Focused Cardiac Ultrasound Diagnosis of Cor Triatriatum Sinistrum in Pediatric Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Thompson Kehrl,

    2015-10-01

    Full Text Available Cardiac arrest in the adolescent population secondary to congenital heart disease (CHD is rare. Focused cardiac ultrasound (FoCUS in the emergency department (ED can yield important clinical information, aid in resuscitative efforts during cardiac arrest and is commonly integrated into the evaluation of patients with pulseless electrical activity (PEA. We report a case of pediatric cardiac arrest in which FoCUS was used to diagnose a critical CHD known as cor triatriatum sinistrum as the likely cause for PEA cardiac arrest and help direct ED resuscitation.

  18. The Cardiac Conduction System: Generation and Conduction of the Cardiac Impulse.

    Science.gov (United States)

    Kennedy, Alan; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond; Moran, Kieran; McLaughlin, James

    2016-09-01

    In this article, the authors outline the key components behind the automated generation of the cardiac impulses and the effect these impulses have on cardiac myocytes. Also, a description of the key components of the normal cardiac conduction system is provided, including the sinoatrial node, the atrioventricular node, the His bundle, the bundle branches, and the Purkinje network. Finally, an outline of how each stage of the cardiac conduction system is represented on the electrocardiogram is described, allowing the reader of the electrocardiogram to translate background information about the normal cardiac conduction system to everyday clinical practice. PMID:27484656

  19. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

    Science.gov (United States)

    Maruyama, Sonomi; Nakamura, Kazuto; Papanicolaou, Kyriakos N; Sano, Soichi; Shimizu, Ippei; Asaumi, Yasuhide; van den Hoff, Maurice J; Ouchi, Noriyuki; Recchia, Fabio A; Walsh, Kenneth

    2016-01-01

    Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1-cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1. PMID:27234440

  20. Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

    Directory of Open Access Journals (Sweden)

    Cher-Ming Liou

    2014-04-01

    Full Text Available To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day. After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse.

  1. Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse.

    Science.gov (United States)

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Ting, Hua; Lee, Shin-Da

    2014-01-01

    To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse. PMID:24722570

  2. Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

    Science.gov (United States)

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Ting, Hua; Lee, Shin-Da

    2014-01-01

    To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse. PMID:24722570

  3. Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging.

    Science.gov (United States)

    Narotsky, David L; Castano, Adam; Weinsaft, Jonathan W; Bokhari, Sabahat; Maurer, Mathew S

    2016-09-01

    Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function. The most common forms of systemic amyloidosis are light-chain and transthyretin-related (ATTR). ATTR can result from an autosomal dominant hereditary transmission of mutated genes in the transthyretin or from a wild-type form of disease (ATTRwt), previously known as senile cardiac amyloidosis. With the aging of the worldwide population, ATTRwt will emerge as the most common type of cardiac amyloidosis that clinicians encounter. Diagnosis of systemic amyloidosis is often delayed, either because of the false assumption that it is a rare disease, or because of misdiagnosis as a result of mistaking it with other conditions. Clinicians must integrate clinical clues from history, physical examination, and common diagnostic tests to raise suspicion for ATTRwt. The historical gold standard for diagnosis of cardiac amyloid is endomyocardial biopsy analysis with pathological distinction of precursor protein type, but this method often results in delayed diagnosis because of the limited availability of expertise to perform and interpret the endomyocardial biopsy specimen. Emerging noninvasive imaging modalities provide easier, accurate screening for ATTRwt. These modalities include advanced echocardiography, using strain imaging and the myocardial contraction fraction; nuclear scintigraphy, which can differentiate between ATTR and light-chain cardiac amyloid; and cardiac magnetic resonance imaging, using extracellular volume measurement, late gadolinium enhancement, and distinct T1 mapping. These novel approaches reveal insights into the prevalence, clinical course, morphological effects, and prognosis of ATTRwt. PMID:27568874

  4. Disruption of Epac1 protects the heart from adenylyl cyclase type 5-mediated cardiac dysfunction.

    Science.gov (United States)

    Cai, Wenqian; Fujita, Takayuki; Hidaka, Yuko; Jin, Huiling; Suita, Kenji; Prajapati, Rajesh; Liang, Chen; Umemura, Masanari; Yokoyama, Utako; Sato, Motohiko; Okumura, Satoshi; Ishikawa, Yoshihiro

    2016-06-17

    Type 5 adenylyl cyclase (AC5) plays an important role in the development of chronic catecholamine stress-induced heart failure and arrhythmia in mice. Epac (exchange protein activated by cAMP), which is directly activated by cAMP independent of protein kinase A, has been recently identified as a novel mediator of cAMP signaling in the heart. However, the role of Epac in AC5-mediated cardiac dysfunction and arrhythmias remains poorly understood. We therefore generated AC5 transgenic mice (AC5TG) with selective disruption of the Epac1 gene (AC5TG-Epac1KO), and compared their phenotypes with those of AC5TG after chronic isoproterenol (ISO) infusion. Decreased cardiac function as well as increased susceptibility to pacing-induced atrial fibrillation (AF) in response to ISO were significantly attenuated in AC5TG-Epac1KO mice, compared to AC5TG mice. Increased cardiac apoptosis and cardiac fibrosis were also concomitantly attenuated in AC5TG-Epac1KO mice compared to AC5TG mice. These findings indicate that Epac1 plays an important role in AC5-mediated cardiac dysfunction and AF susceptibility. PMID:27117748

  5. Cardiac molecular-acclimation mechanisms in response to swimming-induced exercise in Atlantic salmon.

    Directory of Open Access Journals (Sweden)

    Vicente Castro

    Full Text Available Cardiac muscle is a principal target organ for exercise-induced acclimation mechanisms in fish and mammals, given that sustained aerobic exercise training improves cardiac output. Yet, the molecular mechanisms underlying such cardiac acclimation have been scarcely investigated in teleosts. Consequently, we studied mechanisms related to cardiac growth, contractility, vascularization, energy metabolism and myokine production in Atlantic salmon pre-smolts resulting from 10 weeks exercise-training at three different swimming intensities: 0.32 (control, 0.65 (medium intensity and 1.31 (high intensity body lengths s(-1. Cardiac responses were characterized using growth, immunofluorescence and qPCR analysis of a large number of target genes encoding proteins with significant and well-characterized function. The overall stimulatory effect of exercise on cardiac muscle was dependent on training intensity, with changes elicited by high intensity training being of greater magnitude than either medium intensity or control. Higher protein levels of PCNA were indicative of cardiac growth being driven by cardiomyocyte hyperplasia, while elevated cardiac mRNA levels of MEF2C, GATA4 and ACTA1 suggested cardiomyocyte hypertrophy. In addition, up-regulation of EC coupling-related genes suggested that exercised hearts may have improved contractile function, while higher mRNA levels of EPO and VEGF were suggestive of a more efficient oxygen supply network. Furthermore, higher mRNA levels of PPARα, PGC1α and CPT1 all suggested a higher capacity for lipid oxidation, which along with a significant enlargement of mitochondrial size in cardiac myocytes of the compact layer of fish exercised at high intensity, suggested an enhanced energetic support system. Training also elevated transcription of a set of myokines and other gene products related to the inflammatory process, such as TNFα, NFκB, COX2, IL1RA and TNF decoy receptor. This study provides the first

  6. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration.

    Science.gov (United States)

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao

    2016-08-01

    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury. PMID:25480318

  7. Clinical study of cardiac diseases during pregnancy

    Directory of Open Access Journals (Sweden)

    Amitha Vijay Kamat

    2016-03-01

    Conclusions: Cardiac diseases in pregnancy constitute high risk pregnancy and require special attention during antepartum, intrapartum and postpartum period. Rheumatic heart disease was the major contribution of cardiac diseases in pregnancy and is seen to be associated with increased maternal morbidity. [Int J Reprod Contracept Obstet Gynecol 2016; 5(3.000: 855-859

  8. Cardiac hydatid cyst revealed by ventricular tachycardia

    OpenAIRE

    Ibn Elhadj, Zied; Boukhris, Marouane; Kammoun, Ikram; Halima, Afef Ben; Addad, Faouzi; Kachboura, Salem

    2013-01-01

    Hydatid disease is a human parasitic infestation caused by the larval stage of Echinococcus Granulosus. The liver and the lungs are the most common locations. Cardiac involvement is rare and accounts for 0.5–2% of all hydatid disease. We report an unusual presentation of cardiac hydatid cyst revealed by ventricular tachycardia in a patient with a history of cerebral hydatid cyst.

  9. Cardiac arrhythmia classification using autoregressive modeling

    OpenAIRE

    Srinivasan Narayanan; Ge Dingfei; Krishnan Shankar M

    2002-01-01

    Abstract Background Computer-assisted arrhythmia recognition is critical for the management of cardiac disorders. Various techniques have been utilized to classify arrhythmias. Generally, these techniques classify two or three arrhythmias or have significantly large processing times. A simpler autoregressive modeling (AR) technique is proposed to classify normal sinus rhythm (NSR) and various cardiac arrhythmias including atrial premature contraction (APC), premature ventricular contraction (...

  10. Cardiac Diseases in People with Intellectual Disability

    Science.gov (United States)

    van den Akker, M.; Maaskant, M. A.; van der Meijden, R. J. M.

    2006-01-01

    Background: In people with ID there is more morbidity than in the general population, including cardiac diseases. Dutch figures on this subject are scarce. Methods: Descriptive study of the prevalence of cardiac diseases in 436 residential clients in Echt, the Netherlands, and comparisons between men and women, age groups, and level and aetiology…

  11. CARDIAC SIZE IN THE SUPINE CHESTFILM

    NARCIS (Netherlands)

    VANDERJAGT, EJ; SMITS, HJ

    1992-01-01

    The aim of this study was to find a normal value for the cardiac size in the supine position because such a standard is hardly known in the literature. Cardiac size in the erect and supine positions were compared in 165 patients in whom both chest radiographs were performed prior to kidney transplan

  12. The Western Denmark Cardiac Computed Tomography Registry

    DEFF Research Database (Denmark)

    Nielsen, Lene Hüche; Nørgaard, Bjarne Linde; Tilsted, Hans Henrik;

    2015-01-01

    BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We...

  13. Fetal cardiac interventions: clinical and experimental research.

    Science.gov (United States)

    Yuan, Shi-Min; Humuruola, Gulimila

    2016-01-01

    Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID:27279868

  14. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick

    2012-02-03

    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  15. 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...

  16. Cardiac Vagal Regulation and Early Peer Status

    Science.gov (United States)

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.

    2007-01-01

    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  17. Coagulopathy and hemostatic monitoring in cardiac surgery

    DEFF Research Database (Denmark)

    Johansson, Pär I; Sølbeck, Sacha; Genet, Gustav; Stensballe, Jakob; Ostrowski, Sisse R

    2012-01-01

    Cardiac surgery with cardiopulmonary bypass (CPB) causes severe derangements in the hemostatic system, which in turn puts the patient at risks of microvascular bleeding. Excessive transfusion and surgical re-exploration after cardiac surgery are potentially associated with a number of adverse...

  18. Athletes at Risk for Sudden Cardiac Death

    Science.gov (United States)

    Subasic, Kim

    2010-01-01

    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to…

  19. Conditional shape models for cardiac motion estimation

    DEFF Research Database (Denmark)

    Metz, C.T.; Baka, N.; Kirisli, H.A.;

    2010-01-01

    We propose a conditional statistical shape model to predict patient specific cardiac motion from the 3D end-diastolic CTA scan. The model is built from 4D CTA sequences by combining atlas based segmentation and 4D registration. Cardiac motion estimation is, for example, relevant in the dynamic al...

  20. Preoperative respiratory physical therapy in cardiac surgery

    NARCIS (Netherlands)

    Hulzebos, H.J.

    2006-01-01

    Cardiac surgery is one of the most common surgical procedures and accounts for more resources expended in cardiovascular medicine than any other single procedure. Because cardiac surgery involves sternal incision and cardiopulmonary bypass, patients usually have a restricted respiratory function in

  1. Cardiac MRI of the athlete's heart

    NARCIS (Netherlands)

    Prakken, N.H.J.

    2010-01-01

    The increase in pre-participation cardiovascular screening using the Lausanne protocol will ultimately lead to an increased use of cardiac MRI and MDCT in the cardiovascular work-up of athletes. The role of cardiac MRI is well established in the evaluation of cardiomyopathies, myocarditis, aortic st

  2. Hemodynamics driven cardiac valve morphogenesis.

    Science.gov (United States)

    Steed, Emily; Boselli, Francesco; Vermot, Julien

    2016-07-01

    Mechanical forces are instrumental to cardiovascular development and physiology. The heart beats approximately 2.6 billion times in a human lifetime and heart valves ensure that these contractions result in an efficient, unidirectional flow of the blood. Composed of endocardial cells (EdCs) and extracellular matrix (ECM), cardiac valves are among the most mechanically challenged structures of the body both during and after their development. Understanding how hemodynamic forces modulate cardiovascular function and morphogenesis is key to unraveling the relationship between normal and pathological cardiovascular development and physiology. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood. Here we review recent discoveries in the mechanobiology of cardiac valve development and introduce the latest technologies being developed in the zebrafish, including live cell imaging and optical technologies, as well as modeling approaches that are currently transforming this field. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26608609

  3. Cardiac Rehabilitation in Older Adults.

    Science.gov (United States)

    Schopfer, David W; Forman, Daniel E

    2016-09-01

    The biology of aging and the pathophysiology of cardiovascular disease (CVD) overlap, with the effect that CVD is endemic in the growing population of older adults. Moreover, CVD in older adults is usually complicated by age-related complexities, including multimorbidity, polypharmacy, frailty, and other intricacies that add to the risks of ambiguous symptoms, deconditioning, iatrogenesis, falls, disability, and other challenges. Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with cardiovascular conditions. Although CR was originally designed primarily as an exercise training program for younger adults after a myocardial infarction or coronary artery bypass surgery, it has evolved as a comprehensive lifestyle program (promoting physical activity as well as education, diet, risk reduction, and adherence) for a broader range of CVD (coronary heart disease, heart failure, and valvular heart disease). It provides a valuable opportunity to address and moderate many of the challenges pertinent for the large and growing population of older adults with CVD. Cardiac rehabilitation promotes physical function (cardiorespiratory fitness as well as strength and balance) that helps overcome disease and deconditioning as well as related vulnerabilities such as disability, frailty, and falls. Similarly, CR facilitates education, monitoring, and guidance to reduce iatrogenesis and promote adherence. Furthermore, CR fosters cognition, socialization, and independence in older patients. Yet despite all its conceptual benefits, CR is significantly underused in older populations. This review discusses benefits and the paradoxical underuse of CR, as well as evolving models of care that may achieve greater application and efficacy. PMID:27297002

  4. Lipid partitioning during cardiac stress.

    Science.gov (United States)

    Kolwicz, Stephen C

    2016-10-01

    It is well documented that fatty acids serve as the primary fuel substrate for the contracting myocardium. However, extensive research has identified significant changes in the myocardial oxidation of fatty acids during acute or chronic cardiac stress. As a result, the redistribution or partitioning of fatty acids due to metabolic derangements could have biological implications. Fatty acids can be stored as triacylglycerols, serve as critical components for biosynthesis of phospholipid membranes, and form the potent signaling molecules, diacylglycerol and ceramides. Therefore, the contribution of lipid metabolism to health and disease is more intricate than a balance of uptake and oxidation. In this review, the available data regarding alterations that occur in endogenous cardiac lipid pathways during the pathological stressors of ischemia-reperfusion and pathological hypertrophy/heart failure are highlighted. In addition, changes in endogenous lipids observed in exercise training models are presented for comparison. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:27040509

  5. Cardiac cachexia: hic et nunc

    Science.gov (United States)

    Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram

    2016-01-01

    Abstract Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

  6. Cardiac cachexia: hic et nunc.

    Science.gov (United States)

    Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram; Lainscak, Mitja

    2016-06-01

    Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

  7. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation–contraction coupling, and cardiac arrhythmias

    OpenAIRE

    Chopra, Nagesh; Yang, Tao; Asghari, Parisa; Moore, Edwin D.; Huke, Sabine; Akin, Brandy; Cattolica, Robert A.; Perez, Claudio F.; Hlaing, Thinn; Knollmann-Ritschel, Barbara E. C.; Jones, Larry R.; Pessah, Isaac N; Allen, Paul D.; Franzini-Armstrong, Clara; Knollmann, Björn C.

    2009-01-01

    Heart muscle excitation–contraction (E-C) coupling is governed by Ca2+ release units (CRUs) whereby Ca2+ influx via L-type Ca2+ channels (Cav1.2) triggers Ca2+ release from juxtaposed Ca2+ release channels (RyR2) located in junctional sarcoplasmic reticulum (jSR). Although studies suggest that the jSR protein triadin anchors cardiac calsequestrin (Casq2) to RyR2, its contribution to E-C coupling remains unclear. Here, we identify the role of triadin using mice with ablation of the Trdn gene (...

  8. [Rhythm disorders and cardiac crypto-malformations].

    Science.gov (United States)

    Davy, J M; Raczka, F; Cung, T T; Combes, N; Bortone, A; Gaty, D

    2005-12-01

    Faced with a cardiac arrhythmia occuring in an apparently healthy heart, it is necessary to perform an anatomical investigation to detect any unsuspected anomalies. Congenital cardiopathy must certainly be excluded, as this is often responsible for rhythm disorders and/or cardiac conduction defects. Similarly, any acquired conditions, cardiomyopathy, or cardiac tumour must be sought. However, the possibility should always be considered of a minimal congenital malformation, which could be repsonsible for: any type of cardiac arrhythmia: rhythm disorder or conduction defect at the atrial, junctional or ventricular level, with a benign or serious prognosis. Unexpected therapeutic difficulties during radiofrequency ablation procedures or at implantation of pacemakers or defibrillators. Together with rhythm studies, the investigation of choice is high quality imaging, either the classic left or right angiography or the more modern cardiac CT or intracardiac mapping. PMID:16433240

  9. Causes of sudden cardiac death in athletes

    Directory of Open Access Journals (Sweden)

    Popović Dejana

    2007-01-01

    Full Text Available Introduction Sudden cardiac death in athletes is a growing problem, despite the huge existing knowledge in medicine and sports. Effects of vigorous physical activity In response to vigorous physical activity, the body undergoes profound morphologic and functional changes. These changes are usually healthy, but sometimes may gravitate to some cardiac diseases. But still, most sudden cardiac deaths are due to previous unknown diseases. Causes of sudden cardiac death The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. Other reasons are congenital coronary artery anomalies, myocarditis, dilatative cardiomyopathy, arrhythmogenic cardiomyopathy of the right ventricle, sarcoidosis, mitral valve prolapse, aortic valve stenosis, atherosclerosis, long QT syndrome, and blunt impact to the chest. Conclusion Bearing in mind the above mentioned, more frequent physical examinations of athletes are recommended.

  10. Direct Tissue Evaluation via Immunofluorescence: in the Diagnosis of Hereditary Transthyretin Cardiac Amyloidosis

    OpenAIRE

    Fradley, Michael G.; Thakuria, Joseph V.; Collins, A. Bernard; Moore, Stephanie A.; Stone, James R.

    2012-01-01

    Multiple precursor proteins have been shown to cause cardiac amyloidosis. The most common forms are due either to immunoglobulin light chains or to transthyretin proteins (either wild-type or mutant forms). Correct subclassification of the amyloid is paramount because treatment differs in accordance with the type of amyloidosis. Indirect diagnostic methods, including serologic analysis, can lead to misdiagnosis. Definitive diagnosis often requires analysis of amyloid in the tissue. We present...

  11. Cardiac electrical stunning is a common feature of cardiac arrhythmias.

    Science.gov (United States)

    Li, Guangping; Liu, Tong; Liu, Enzhao

    2006-01-01

    There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias. PMID:16759818

  12. Inclusion body myositis, muscle blood vessel and cardiac amyloidosis, and transthyretin Val122Ile allele.

    Science.gov (United States)

    Askanas, V; Engel, W K; Alvarez, R B; Frangione, B; Ghiso, J; Vidal, R

    2000-04-01

    Typical of sporadic inclusion body myositis muscle biopsies are vacuolated muscle fibers containing intracellular amyloid deposits and accumulations of "Alzheimer-characteristic" proteins. There is no muscle blood vessel or cardiac amyloidosis. We report on a 70-year-old African-American man homozygous for the transthyretin Val122Ile allele who has both sporadic inclusion body myositis and cardiac amyloidosis. His unique pathological features included transthyretin immunoreactivity in prominent muscle blood vessel amyloid and congophilic amyloid deposits within vacuolated muscle fibers. PMID:10762172

  13. A mighty small heart: the cardiac proteome of adult Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Anthony Cammarato

    Full Text Available Drosophila melanogaster is emerging as a powerful model system for the study of cardiac disease. Establishing peptide and protein maps of the Drosophila heart is central to implementation of protein network studies that will allow us to assess the hallmarks of Drosophila heart pathogenesis and gauge the degree of conservation with human disease mechanisms on a systems level. Using a gel-LC-MS/MS approach, we identified 1228 protein clusters from 145 dissected adult fly hearts. Contractile, cytostructural and mitochondrial proteins were most abundant consistent with electron micrographs of the Drosophila cardiac tube. Functional/Ontological enrichment analysis further showed that proteins involved in glycolysis, Ca(2+-binding, redox, and G-protein signaling, among other processes, are also over-represented. Comparison with a mouse heart proteome revealed conservation at the level of molecular function, biological processes and cellular components. The subsisting peptidome encompassed 5169 distinct heart-associated peptides, of which 1293 (25% had not been identified in a recent Drosophila peptide compendium. PeptideClassifier analysis was further used to map peptides to specific gene-models. 1872 peptides provide valuable information about protein isoform groups whereas a further 3112 uniquely identify specific protein isoforms and may be used as a heart-associated peptide resource for quantitative proteomic approaches based on multiple-reaction monitoring. In summary, identification of excitation-contraction protein landmarks, orthologues of proteins associated with cardiovascular defects, and conservation of protein ontologies, provides testimony to the heart-like character of the Drosophila cardiac tube and to the utility of proteomics as a complement to the power of genetics in this growing model of human heart disease.

  14. Current perspectives on cardiac amyloidosis

    OpenAIRE

    Guan, Jian; Mishra, Shikha; Falk, Rodney H.; Liao, Ronglih

    2011-01-01

    Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either...

  15. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, N. V.; Saner, H.; Pedersen, S. S.;

    2015-01-01

    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health- related quality...... of life (HRQoL) and prognosis in patients with establishedCHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system....... Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening...

  16. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, Nana; Saner, Hugo; Pedersen, Susanne S.;

    2015-01-01

    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality...... of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system....... Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening...

  17. Cardiac Rehabilitation: Improving Function and Reducing Risk.

    Science.gov (United States)

    Servey, Jessica T; Stephens, Mark

    2016-07-01

    Cardiac rehabilitation is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. The overall goals focus on improving daily function and reducing cardiovascular risk factors. Cardiac rehabilitation includes interventions aimed at lowering blood pressure and improving lipid and diabetes mellitus control, with tobacco cessation, behavioral counseling, and graded physical activity. The physical activity component typically involves 36 sessions over 12 weeks, during which patients participate in supervised exercise under cardiac monitoring. There are also intensive programs that include up to 72 sessions lasting up to 18 weeks, although these programs are not widely available. Additional components of cardiac rehabilitation include counseling on nutrition, screening for and managing depression, and assuring up-to-date immunizations. Cardiac rehabilitation is covered by Medicare and recommended for patients following myocardial infarction, bypass surgery, and stent placement, and for patients with heart failure, stable angina, and several other conditions. Despite proven benefits in mortality rates, depression, functional capacity, and medication adherence, rates of referral for cardiac rehabilitation are suboptimal. Groups less likely to be referred are older adults, women, patients who do not speak English, and persons living in areas where cardiac rehabilitation is not locally available. Additionally, primary care physicians refer patients less often than cardiologists and cardiothoracic surgeons. PMID:27386722

  18. A mechanical simulator of cardiac wall kinematics.

    Science.gov (United States)

    Cutrì, Elena; Bagnoli, Paola; Marcelli, Emanuela; Biondi, Federico; Cercenelli, Laura; Costantino, Maria Laura; Plicchi, Gianni; Fumero, Roberto

    2010-01-01

    Aim of this study is to develop a mechanical simulator (MS) reproducing cardiac wall kinematics [i.e., radial (R), longitudinal (L) and rotational (RT) motions] to test piezoelectric gyroscopic sensors (GS) that are able to measure cardiac torsion that has proved to be a sensitive index of cardiac performance. The MS consists of three brushless motors controlled by a dedicated software either separately or simultaneously reproducing the three main cardiac wall movements (R, L, RT) obtained by implementing different physiologic or pathologic velocity profiles derived from in vivo data. GS accuracy (max % error) was experimentally tested by connecting it to the MS driven in velocity in different working conditions [i.e., cardiac period (515-1030 ms), RT angle (4-16 degrees), GS axis inclination (0-90 degrees) with respect to the cardiac rotation axis]. The MS reproduced the tested velocity profiles well. The GS showed high accuracy in measuring both physiologic and pathologic RT velocity profiles, whereas they proved insensitive to R and L motions. GS axis inclination influenced measurements; however, it was possible to correct this taking the inclination angle cosine into account. The MS proved to be a useful tool to study cardiac wall kinematics and test GS reliability with a view to in vivo application. PMID:20404720

  19. MRS: a noninvasive window into cardiac metabolism.

    Science.gov (United States)

    van Ewijk, Petronella A; Schrauwen-Hinderling, Vera B; Bekkers, Sebastiaan C A M; Glatz, Jan F C; Wildberger, Joachim E; Kooi, M Eline

    2015-07-01

    A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS. PMID:26010681

  20. Evolutionary origin of cardiac malformations.

    Science.gov (United States)

    Taussig, H B

    1988-10-01

    The author has proposed in previous publications that isolated cardiac malformations have an evolutionary origin. This is partly supported by the fact that isolated cardiac malformations found in humans occur also in other placental mammals as well as in birds. External gross examination of the heart in just over 5,000 birds was carried out during a 3 year period. Anomalies included one instance of duplicate hearts, two specimens in which no heart could be identified and in a fourth, a yellow-rumped warbler, the heart lay in the neck outside of the thoracic cavity. Published reports of similar occurrences of an ectopically placed heart concern birds, cattle and humans. The fact that various species of both placental mammals and birds show evidence of heritability for heart defects, and that these species cannot interbreed, combined with the fact that birds and mammals have many similar malformations, points to either a common external causative factor or a common origin. Genes that code the malformed heart must be transmitted with that part of the genetic makeup common to all birds and mammals. Malformations caused by teratogens produce widespread organ injury to a potentially normal embryo whereas the evolutionary malformation is an organ-specific anomaly in an otherwise normal mammal or bird and occurs in widely separated species. The implications of this theory are important for parents of children with an isolated congenital heart defect who may have ingested one or another drug or chemical or have been exposed to toxins or infectious agents before or after conception of the affected offspring. PMID:3047192

  1. Cardiac imaging: Current and emerging applications

    Directory of Open Access Journals (Sweden)

    Jankharia B

    2010-01-01

    Full Text Available Cardiac magnetic resonance imaging (MRI and computed tomography (CT scan have made big inroads as modalities used for evaluation of various pathologies of the heart. Cardiac MRI is typically used for perfusion and viability studies as well as to study various cardiomyopathies, valvular diseases and the pericardium. It has been used in the evaluation of congenital heart diseases over the last two decades. Cardiac CT is used mainly for the evaluation of the coronary arteries, typically in the setting of "to rule out coronary artery disease".

  2. Cardiac Amyloidosis Presenting With Cardiogenic Shock.

    Science.gov (United States)

    Afzal, Ashwad; Brener, Sorin J; Narula, Navneet; Worku, Berhane; Gulkarov, Iosif

    2016-01-01

    Cardiac amyloidosis is an infiltrative disorder of the myocardium. It is the result of one of 4 types of amyloidosis: primary systemic (immunoglobulin light chain), secondary, familial (hereditary), or senile. Cardiac amyloidosis ultimately causes congestive heart failure due to irreversible restrictive cardiomyopathy. Because of the rapid progression of the disease, early recognition and determination of underlying etiology are important for tailored therapy. Current interventions range from conservative heart failure management to autologous stem cell and heart transplantation. We present a case of cardiac amyloidosis accompanying undiagnosed multiple myeloma to illustrate the rapid progression of the disease and the complexities of diagnosing and treating this disorder. PMID:26177555

  3. More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair.

    Science.gov (United States)

    Kishore, Raj; Khan, Mohsin

    2016-01-22

    Stem cell therapy provides immense hope for regenerating the pathological heart, yet has been marred by issues surrounding the effectiveness, unclear mechanisms, and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been used with varied success. Cell-free components, such as exosomes enriched in proteins, messenger RNAs, and miRs characteristic of parental stem cells, represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively used to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes, including their potential benefits and limitations to develop a potentially viable therapy for cardiovascular problems. PMID:26838317

  4. [Drug with a high metabolic activity, cocarnit, in the treatment of diabetic cardiac autonomic neuropathy].

    Science.gov (United States)

    Popov, S V; Melekhovets', O K; Demikhova, N V; Vynnychenko, L B

    2012-01-01

    Left ventricular diastolic dysfunction in patients with diabetes is formed in the absence of atherosclerotic changes as a consequence of diabetic cardiac autonomic neuropathy in the early stages of diabetes. Progression of autonomic cardiac neuropathy in cardio-vascular type is associated with the violation of energy supply of cells, protein synthesis, electrolyte exchange, the exchange of trace elements, oxidation reduction processes, oxygen-transport function of blood, so that metabolic therapy is carried out to optimize the processes of formation and energy costs. The drug cocarnit activates processes of aerobic oxidation of glucose, as well as providing regulatory influence on the oxidation of fatty acids. Applying of cocarnit in complex therapy in patients with diabetic cardiac autonomic neuropathy found improvement of left ventricular diastolic function, and positive dynamics in the efferent activity balance of the sympathetic and parasympathetic control of heart rate variability, which provides the regression of clinical symptoms. PMID:23356142

  5. The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation

    International Nuclear Information System (INIS)

    Prelamin A processing is unique amongst mammalian proteins and results in the production of a farnesylated and carboxymethylated peptide. We examined the effect of pathogenic LMNA mutations on prelamin A processing, and of the covalently modified peptide on cardiac and skeletal myoblast differentiation. Here we report a mutation associated with dilated cardiomyopathy prevents prelamin A peptide production. In addition, topical application of the covalently modified C-terminal peptide to proliferating skeletal and cardiac myoblasts induced myotube and striated tissue formation, respectively. Western blot analysis revealed that skeletal and cardiac myoblasts are the first cell lines examined to contain unprocessed prelamin A, and immunostaining of peptide-treated cells revealed a previously unidentified role for prelamin A in cytoskeleton formation and intercellular organization. These results demonstrate a direct role for prelamin A in myoblast differentiation and indicate the prelamin A peptide may have therapeutic potential

  6. Cardiac carcinoid: tricuspid delayed hyperenhancement on cardiac 64-slice multidetector CT and magnetic resonance imaging.

    LENUS (Irish Health Repository)

    Martos, R

    2012-02-01

    INTRODUCTION: Carcinoid heart disease is a rare condition in adults. Its diagnosis can be easily missed in a patient presenting to a primary care setting. We revised the advantages of using coronary multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (MRI) in diagnosing this condition. MATERIALS AND METHODS: We studied a 65-year-old patient with carcinoid heart disease and right heart failure using transthoracic Doppler-echocardiogram, cardiac MDCT and MRI. Cardiac echocardiogram revealed marked thickening and retraction of the tricuspid leaflets with dilated right atrium and ventricle. Cardiac MDCT and MRI demonstrated fixation and retraction of the tricuspid leaflets with delayed contrast hyperenhancement of the tricuspid annulus. CONCLUSION: This case demonstrates fascinating imaging findings of cardiac carcinoid disease and highlights the increasing utility of contrast-enhanced MRI and cardiac MDCT in the diagnosis of this interesting condition.

  7. 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

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

    International Nuclear Information System (INIS)

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

  9. Inhibition of CaMKII does not attenuate cardiac hypertrophy in mice with dysfunctional ryanodine receptor.

    Directory of Open Access Journals (Sweden)

    Asima Chakraborty

    Full Text Available In cardiac muscle, the release of calcium ions from the sarcoplasmic reticulum through ryanodine receptor ion channels (RyR2s leads to muscle contraction. RyR2 is negatively regulated by calmodulin (CaM and by phosphorylation of Ca2+/CaM-dependent protein kinase II (CaMKII. Substitution of three amino acid residues in the CaM binding domain of RyR2 (RyR2-W3587A/L3591D/F3603A, RyR2ADA impairs inhibition of RyR2 by CaM and results in cardiac hypertrophy and early death of mice carrying the RyR2ADA mutation. To test the cellular function of CaMKII in cardiac hypertrophy, mutant mice were crossed with mice expressing the CaMKII inhibitory AC3-I peptide or the control AC3-C peptide in the myocardium. Inhibition of CaMKII by AC3-I modestly reduced CaMKII-dependent phosphorylation of RyR2 at Ser-2815 and markedly reduced CaMKII-dependent phosphorylation of SERCA2a regulatory subunit phospholamban at Thr-17. However the average life span and heart-to-body weight ratio of Ryr2ADA/ADA mice expressing the inhibitory peptide were not altered compared to control mice. In Ryr2ADA/ADA homozygous mice, AC3-I did not alter cardiac morphology, enhance cardiac function, improve sarcoplasmic reticulum Ca2+ handling, or suppress the expression of genes implicated in cardiac remodeling. The results suggest that CaMKII was not required for the rapid development of cardiac hypertrophy in Ryr2ADA/ADA mice.

  10. Assembly of a functional 3D primary cardiac construct using magnetic levitation

    Directory of Open Access Journals (Sweden)

    Matthew Hogan

    2016-07-01

    Full Text Available Easily assembled organotypic co-cultures have long been sought in medical research. In vitro tissue constructs with faithful representation of in vivo tissue characteristics are highly desirable for screening and characteristic assessment of a variety of tissue types. Cardiac tissue analogs are particularly sought after due to the phenotypic degradation and difficulty of culture of primary cardiac myocytes. This study utilized magnetic nanoparticles and primary cardiac myocytes in order to levitate and culture multicellular cardiac aggregates (MCAs. Cells were isolated from 2 day old Sprague Dawley rat hearts and subsequently two groups were incubated with either C1: 33 µL nanoshell/million cells or C2: 50 µL nanoshell/million cells. Varying numbers of cells for each concentration were cultured in a magnetic field in a 24 well plate and observed over a period of 12 days. Constructs generally formed spherical structures. Masson’s trichrome staining of a construct shows the presence of extracellular matrix protein, indicating the presence of functional fibroblasts. Many constructs exhibited noticeable contraction after 4 days of culture and continued contracting noticeably past day 9 of culture. Noticeable contractility indicates the presence of functional primary cardiac myocytes in culture. Phenotypic conservation of cardiac cells was ascertained using IHC staining by α-actinin and collagen. CD31 and fibrinogen were probed in order to assess localization of fibroblasts and endothelial cells. The study verifies a protocol for the use of magnetic levitation in order to rapidly assemble 3D cardiac like tissue with phenotypic and functional stability.

  11. Differentiation of cardiac thrombus from cardiac tumor combining cardiac MRI and 18F-FDG-PET/CT Imaging.

    Science.gov (United States)

    Rinuncini, Massimo; Zuin, Marco; Scaranello, Fiorenzo; Fejzo, Majlinda; Rampin, Lucia; Rubello, Domenico; Faggian, Giuseppe; Roncon, Loris

    2016-06-01

    Radiological differentiation of an unknown cardiac masse is often a challenging issue. 18F-FDG-PET/CT imaging was performed to evaluate a left ventricle mass visualized on transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) in a patient with an history of ischemic heart disease. The metabolically inert area on the PET/CT, corresponding to the relatively homogenous hypodensity in the LV, was thought to represent an old organized LV thrombus. Histopathological examination confirmed the imaging diagnosis. PMID:27038712

  12. IS CONSANGUINEOUS MARRIAGE RESPONSIBLE FOR CONGENITAL CARDIAC AND EXTRA-CARDIAC ANOMALIES?

    OpenAIRE

    Nutan Nalini; Sudha

    2016-01-01

    BACKGROUND This article is about the stillbirth in which we found significant numbers of cardiac as well as extracardiac defects, in combination or separately. In this article, we would like to emphasize the anomalies found in consanguineous marriages. AIM To correlate the prevalence of cardiac as well as extracardiac anomalies in consanguineous marriages. Especially, here we would like to focus on the cardiac lesions. MATERIAL AND METHOD The study was ca...

  13. MicroRNA-9 regulates cardiac fibrosis by targeting PDGFR-β in rats.

    Science.gov (United States)

    Wang, Lei; Ma, LiKun; Fan, Hai; Yang, Zhe; Li, LongWei; Wang, HanZhang

    2016-06-01

    The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix (ECM) are the main pathological characteristics of cardiac fibrosis. In recent years, microRNAs (miRNAs) have been found to be a new kind of regulator in cardiac fibrosis. The purpose of this study was to investigate the role of microRNA-9 (miR-9) in the process of cardiac fibrosis and its mechanism. Treatment of cultured neonatal rat CFs with PDGF-BB or serum suppressed the expression of miR-9. Overexpression of miR-9 obviously inhibited neonatal rat CFs proliferation and collagen production as detected by MTT assays, qRT-PCR, and western blotting. The effects of miR-9 in CFs were abrogated by co-transfection with miR-9 inhibitors. Overexpression of miR-9 reduced the mRNA and protein levels of PDGFR-βand its downstream protein, extracellular signal-regulated kinase (ERK) 1/2. Silencing PDGFR-βby small interfering RNA mimicked the anti-fibrotic action of miR-9, whereas overexpression of PGDFR-β canceled the effect of miR-9 in cultured CFs. Dual-luciferase reporter assays showed that PDGFR-βwas a direct target of miR-9. Overexpression of miR-9 inhibited cardiac fibrosis by targeting PDGFR-β, indicating that miR-9 might play a role in the treatment of cardiac fibrosis. PMID:26896308

  14. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    Science.gov (United States)

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. PMID:25120320

  15. Microengineered in vitro model of cardiac fibrosis through modulating myofibroblast mechanotransduction.

    Science.gov (United States)

    Zhao, Hui; Li, Xiaokang; Zhao, Shan; Zeng, Yang; Zhao, Long; Ding, Haiyan; Sun, Wei; Du, Yanan

    2014-12-01

    Cardiac fibrosis greatly impairs normal heart function post infarction and there is no effective anti-fibrotic drug developed at present. The current therapies for cardiac infarction mainly take effect by eliminating occlusion in coronary artery by thrombolysis drugs, vascular stent grafting or heart bypass operation, which are capable to provide sufficient blood flow for intact myocardium yet showed subtle efficacy in ameliorating fibrosis condition. The advances of in vitro cell/tissue models open new avenues for drug assessment due to the low cost, good controllability and availability as well as the convenience for operation as compared to the animal models. To our knowledge, no proper biomimetic in vitro cardiac fibrosis model has been reported yet. Here we engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts, and the fibrogenesis was recapitulated by patterning the substrate rigidity which mimicked the mechanical heterogeneity of myocardium post-infarction. Various biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK) pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility of applying this platform in screening anti-fibrosis drugs. PMID:25378063

  16. Microengineered in vitro model of cardiac fibrosis through modulating myofibroblast mechanotransduction

    International Nuclear Information System (INIS)

    Cardiac fibrosis greatly impairs normal heart function post infarction and there is no effective anti-fibrotic drug developed at present. The current therapies for cardiac infarction mainly take effect by eliminating occlusion in coronary artery by thrombolysis drugs, vascular stent grafting or heart bypass operation, which are capable to provide sufficient blood flow for intact myocardium yet showed subtle efficacy in ameliorating fibrosis condition. The advances of in vitro cell/tissue models open new avenues for drug assessment due to the low cost, good controllability and availability as well as the convenience for operation as compared to the animal models. To our knowledge, no proper biomimetic in vitro cardiac fibrosis model has been reported yet. Here we engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts, and the fibrogenesis was recapitulated by patterning the substrate rigidity which mimicked the mechanical heterogeneity of myocardium post-infarction. Various biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK) pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility of applying this platform in screening anti-fibrosis drugs. (paper)

  17. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function

    OpenAIRE

    Mayfield, Audrey E.; Tilokee, Everad L.; Latham, Nicholas; McNeill, Brian; Lam, Bu-Khanh; Ruel, Marc; Suuronen, Erik J; Courtman, David W.; Stewart, Duncan J.; Davis, Darryl R.

    2013-01-01

    Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the...

  18. Quantification in non-invasive cardiac imaging: CT and MR

    OpenAIRE

    Rossi, Alexia

    2013-01-01

    markdownabstract__Abstract__ The diagnosis and management of cardiac disease require a precise assessment of morphological and functional cardiac parameters. This thesis is divided in three parts. Part I emphasizes the role of cardiac computed tomography (CT) in the diagnosis of patients with ischemic heart disease. Part 2 describes the role of cardiac magnetic resonance (CMR) and cardiac CT in the diagnosis, interventional planning, and follow-up of patients with aortic valve stenosis. Part ...

  19. Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

    OpenAIRE

    José Manuel Calderón-Montaño; Estefanía Burgos-Morón; Manuel Luis Orta; Dolores Maldonado-Navas; Irene García-Domínguez; Miguel López-Lázaro

    2014-01-01

    Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typ...

  20. Assembly of the Cardiac Intercalated Disk during Pre- and Postnatal Development of the Human Heart

    Science.gov (United States)

    Vreeker, Arnold; van Stuijvenberg, Leonie; Hund, Thomas J.; Mohler, Peter J.; Nikkels, Peter G. J.; van Veen, Toon A. B.

    2014-01-01

    Background In cardiac muscle, the intercalated disk (ID) at the longitudinal cell-edges of cardiomyocytes provides as a macromolecular infrastructure that integrates mechanical and electrical coupling within the heart. Pathophysiological disturbance in composition of this complex is well known to trigger cardiac arrhythmias and pump failure. The mechanisms underlying assembly of this important cellular domain in human heart is currently unknown. Methods We collected 18 specimens from individuals that died from non-cardiovascular causes. Age of the specimens ranged from a gestational age of 15 weeks through 11 years postnatal. Immunohistochemical labeling was performed against proteins comprising desmosomes, adherens junctions, the cardiac sodium channel and gap junctions to visualize spatiotemporal alterations in subcellular location of the proteins. Results Changes in spatiotemporal localization of the adherens junction proteins (N-cadherin and ZO-1) and desmosomal proteins (plakoglobin, desmoplakin and plakophilin-2) were identical in all subsequent ages studied. After an initial period of diffuse and lateral labelling, all proteins were fully localized in the ID at approximately 1 year after birth. Nav1.5 that composes the cardiac sodium channel and the gap junction protein Cx43 follow a similar pattern but their arrival in the ID is detected at (much) later stages (two years for Nav1.5 and seven years for Cx43, respectively). Conclusion Our data on developmental maturation of the ID in human heart indicate that generation of the mechanical junctions at the ID precedes that of the electrical junctions with a significant difference in time. In addition arrival of the electrical junctions (Nav1.5 and Cx43) is not uniform since sodium channels localize much earlier than gap junction channels. PMID:24733085