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Sample records for cardiac ryanodine receptor

  1. Spatial localization of ryanodine receptors in human cardiac cells.

    Science.gov (United States)

    Vallmitjana, A; Nolla, C; Herraiz-Martínez, A; Hove-Madsen, L; Benítez, R

    2015-08-01

    We present a novel image processing method to determine the location of ryanodine receptors in cardiac cells. A semi-automatic manual validation by an expert has been used in order to establish the performance of the segmentation method. The approach provides high accuracy under different experimental conditions and it is robust to common sources of noise including experimental, molecular and biological fluctuations. PMID:26737732

  2. Structural and functional characterization of the purified cardiac ryanodine receptor-Ca2+ release channel complex.

    Science.gov (United States)

    Anderson, K; Lai, F A; Liu, Q Y; Rousseau, E; Erickson, H P; Meissner, G

    1989-01-15

    Using density gradient centrifugation and [3H]ryanodine as a specific marker, the ryanodine receptor-Ca2+ release channel complex from Chaps-solubilized canine cardiac sarcoplasmic reticulum (SR) has been purified in the form of an approximately 30 S complex, comprised of Mr approximately 400,000 polypeptides. Purification resulted in a specific activity of approximately 450 pmol bound ryanodine/mg of protein, a 60-70% recovery of ryanodine binding activity, and retention of the high affinity ryanodine binding site (KD = 3 nM). Negative stain electron microscopy revealed a 4-fold symmetric, four-leaf clover structure, which could fill a box approximately 30 x 30 nm and was thus morphologically similar to the SR-transverse-tubule, junctionally associated foot structure. The structural, sedimentation, and ryanodine binding data strongly suggest there is one high affinity ryanodine binding site/30 S complex, comprised of four Mr approximately 400,000 subunits. Upon reconstitution into planar lipid bilayers, the purified complex exhibited a Ca2+ conductance (70 pS in 50 mM Ca2+) similar to that of the native cardiac Ca2+ release channel (75 pS). The reconstituted complex was also found to conduct Na+ (550 pS in 500 mM Na+) and often to display complex Na+ subconducting states. The purified channel could be activated by micromolar Ca2+ or millimolar ATP, inhibited by millimolar Mg2+ or micromolar ruthenium red, and modified to a long-lived open subconducting state by ryanodine. The sedimentation, subunit composition, morphological, and ryanodine binding characteristics of the purified cardiac ryanodine receptor-Ca2+ release channel complex were similar to those previously described for the purified ryanodine receptor-Ca2+ release channel complex from fast-twitch skeletal muscle. PMID:2463249

  3. Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels

    OpenAIRE

    Meissner, Gerhard; Pasek, Daniel A.; Yamaguchi, Naohiro; Ramachandran, Srinivas; Dokholyan, Nikolay V.; Tripathy, Ashutosh

    2009-01-01

    The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium release channels contain a single, conserved calmodulin (CaM) binding domain, yet are differentially regulated by CaM. Here, we report that high-affinity [35S]CaM binding to RyR1 is driven by favorable enthalpic and entropic contributions at Ca2+ concentrations from

  4. Surface charge potentiates conduction through the cardiac ryanodine receptor channel

    OpenAIRE

    1994-01-01

    Single channel currents through cardiac sarcoplasmic reticulum (SR) Ca2+ release channels were measured in very low levels of current carrier (e.g., 1 mM Ba2+). The hypothesis that surface charge contributes to these anomalously large single channel currents was tested by changing ionic strength and surface charge density. Channel identity and sidedness was pharmacologically determined. At low ionic strength (20 mM Cs+), Cs+ conduction in the lumen-->myoplasm (L-->M) direction was significant...

  5. CaMKII Regulation of Cardiac Ryanodine Receptors and Inositol Triphosphate Receptors

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    Emmanuel eCamors

    2014-05-01

    Full Text Available Ryanodine receptors (RyRs and inositol triphosphate receptors (InsP3Rs are structurally related intracellular calcium release channels that participate in multiple primary or secondary amplified Ca2+ signals, triggering muscle contraction and oscillatory Ca2+ waves, or activating transcription factors. In the heart, RyRs play an indisputable role in the process of excitation-contraction coupling as the main pathway for Ca2+ release from sarcoplasmic reticulum (SR, and a less prominent role in the process of excitation-transcription coupling. Conversely, InsP3Rs are believed to contribute in subtle ways, only, to contraction of the heart, and in more important ways to regulation of transcription factors. Because uncontrolled activity of either RyRs or InsP3Rs may elicit life-threatening arrhythmogenic and/or remodeling Ca2+ signals, regulation of their activity is of paramount importance for normal cardiac function. Due to their structural similarity, many regulatory factors, accessory proteins, and posttranslational processes are equivalent for RyRs and InsP3Rs. Here we discuss regulation of RyRs and InsP3Rs by CaMKII phosphorylation, but touch on other kinases whenever appropriate. CaMKII is emerging as a powerful modulator of RyR and InsP3R activity but interestingly, some of the complexities and controversies surrounding phosphorylation of RyRs also apply to InsP3Rs, and a clear-cut effect of CaMKII on either channel eludes investigators for now. Nevertheless, some effects of CaMKII on global cellular activity, such as SR Ca2+ leak or force-frequency potentiation, appear clear now, and this constrains the limits of the controversies and permits a more tractable approach to elucidate the effects of phosphorylation at the single channel level.

  6. Cardiac ryanodine receptor in metabolic syndrome: is JTV519 (K201 future therapy?

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    Dincer UD

    2012-04-01

    Full Text Available U Deniz DincerDepartment of Pharmacology, Ufuk University School of Medicine. Mevlana Bulvari, Balgat, Ankara, TurkeyAbstract: Metabolic syndrome is characterized by a combination of obesity, hypertension, insulin resistance, dyslipidemia, and impaired glucose tolerance. This multifaceted syndrome is often accompanied by a hyperdynamic circulatory state characterized by increased blood pressure, total blood volume, cardiac output, and metabolic tissue demand. Experimental, epidemiological, and clinical studies have demonstrated that patients with metabolic syndrome have significantly elevated cardiovascular morbidity and mortality rates. One of the main and frequent complications seen in metabolic syndrome is cardiovascular disease. The primary endpoints of cardiometabolic risk are coronary and peripheral arterial disease, myocardial infarction, congestive heart failure, arrhythmia, and stroke. Alterations in expression and/or functioning of several key proteins involved in regulating and maintaining ionic homeostasis can cause cardiac disturbances. One such group of proteins is known as ryanodine receptors (intracellular calcium release channels, which are the major channels through which Ca2+ ions leave the sarcoplasmic reticulum, leading to cardiac muscle contraction. The economic cost of metabolic syndrome and its associated complications has a significant effect on health care budgets. Improvements in body weight, blood lipid profile, and hyperglycemia can reduce cardiometabolic risk. However, constant hyperadrenergic stimulation still contributes to the burden of disease. Normalization of the hyperdynamic circulatory state with conventional therapies is the most reasonable therapeutic strategy to date. JTV519 (K201 is a newly developed 1,4-benzothiazepine drug with antiarrhythmic and cardioprotective properties. It appears to be very effective in not only preventing but also in reversing the characteristic myocardial changes and preventing

  7. Amphibian ryanodine receptor isoforms are related to those of mammalian skeletal or cardiac muscle.

    Science.gov (United States)

    Lai, F A; Liu, Q Y; Xu, L; el-Hashem, A; Kramarcy, N R; Sealock, R; Meissner, G

    1992-08-01

    The ryanodine receptor (RyR)-Ca2+ release channels of frog skeletal muscle have been purified as 30S protein complexes comprised of two high molecular weight polypeptides. The upper and lower bands of the frog doublet comigrated on sodium dodecyl sulfate polyacylamide gels with the mammalian skeletal and cardiac RyR polypeptides, respectively. Immunoblot analysis showed that a polyclonal antiserum to the rat skeletal RyR preferentially cross-reacted with the upper band, whereas monoclonal antibodies to the canine cardiac RyR preferentially cross-reacted with the lower band of the frog receptor doublet. Immunoprecipitation studies indicated the presence of two homooligomer 30S RyR complexes comprised of either the lower or upper polypeptide band of the frog doublet, and immunocytochemical staining revealed their colocalization in frog gastrocnemius muscle. After planar lipid bilayer reconstitution of the 30S frog RyR, single-channel currents were observed that exhibited a Na+ and Ca2+ conductance and pharmacological characteristics similar to those of the mammalian skeletal and cardiac Ca2+ release channels. These results suggest that amphibian skeletal muscle expresses two distinct RyR isoforms that share epitopes in common with the mammalian skeletal or cardiac RyR. PMID:1325114

  8. 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.

  9. The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis.

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    Tunwell, R E; Wickenden, C; Bertrand, B M; Shevchenko, V I; Walsh, M B; Allen, P D; Lai, F A

    1996-09-01

    Rapid Ca2+ efflux from intracellular stores during cardiac muscle excitation-contraction coupling is mediated by the ryanodine-sensitive calcium-release channel, a large homotetrameric complex present in the sarcoplasmic reticulum. We report here the identification, primary structure and topological analysis of the ryanodine receptor-calcium release channel from human cardiac muscle (hRyR-2). Consistent with sedimentation and immunoblotting studies on the hRyR-2 protein, sequence analysis of ten overlapping cDNA clones reveals an open reading frame of 14901 nucleotides encoding a protein of 4967 amino acid residues with a predicted molecular mass of 564 569 Da for hRyR-2. In-frame insertions corresponding to eight and ten amino acid residues were found in two of the ten cDNAs isolated, suggesting that novel, alternatively spliced transcripts of the hRyR-2 gene might exist. Six hydrophobic stretches, which are present within the hRyR-2 C-terminal 500 amino acids and are conserved in all RyR sequences, may be involved in forming the transmembrane domain that constitutes the Ca(2+)-conducting pathway, in agreement with competitive ELISA studies with a RyR-2-specific antibody. Sequence alignment of hRyR-2 with other RyR isoforms indicates a high level of overall identity within the RyR family, with the exception of two important regions that exhibit substantial variability. Phylogenetic analysis suggests that the RyR-2 isoform diverged from a single ancestral gene before the RyR-1 and RyR-3 isoforms to form a distinct branch of the RyR family tree. PMID:8809036

  10. Posttranslational modifications of cardiac ryanodine receptors: Ca2+ signaling and EC-coupling

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    Niggli, Ernst; Ullrich, Nina D.; Gutierrez, D.; Kyrychenko, Sergii; Poláková, Eva; Shirokova, Natalia

    2012-01-01

    In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca2+ release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca2+-induced Ca2+ release mechanism and contribute a large fraction of the Ca2+ required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca2+ sensitivity. Presently, research in a number of laboratories is focussed on RyR phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by reactive oxygen and nitrogen species (ROS / RNS). Both classes of posttranslational modifications are thought to play important roles in the physiological regulation of channel activity, but are also known to provoke abnormal alterations during various diseases. Only recently it was realized that several types of posttranslational modifications are tightly connected and form synergistic (or antagonistic) feed-back loops resulting in additive and potentially detrimental downstream effects. This review summarizes recent findings on such posttranslational modifications, attempts to bridge molecular with cellular findings, and opens a perspective for future work trying to understand the ramifications of crosstalk in these multiple signaling pathways. Clarifying these complex interactions will be important in the development of novel therapeutic approaches, since this may form the foundation for the implementation of multi-pronged treatment regimes in the future. PMID:22960642

  11. Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death.

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    Marks, A R

    2001-04-01

    Calcium (Ca2+) ions are second messengers in signaling pathways in all types of cells. They regulate muscle contraction, electrical signals which determine the cardiac rhythm and cell growth pathways in the heart. In the past decade cDNA cloning has provided clues as to the molecular structure of the intracellular Ca2+ release channels (ryanodine receptors, RyR, and inositol 1,4,5-trisphosphate receptors, IP3R) on the sarcoplasmic and endoplasmic reticulum (SR/ER) and an understanding of how these molecules regulate Ca2+ homeostasis in the heart is beginning to emerge. The intracellular Ca2+ release channels form a distinct class of ion channels distinguished by their structure, size, and function. Both RyRs and IP3Rs have gigantic cytoplasmic domains that serve as scaffolds for modulatory proteins that regulate the channel pore located in the carboxy terminal 10% of the channel sequence. The channels are tetramers comprised of four RyR or IP3R subunits. RyR2 is required for excitation-contraction (EC) coupling in the heart. Using co-sedimentation and co-immunoprecipitation we have defined a macromolecular complex comprised of RyR2, FKBP12.6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein mAKAP. We have shown that protein kinase A (PKA) phosphorylation of RyR2 dissociates FKBP12.6 and regulates the channel open probability (P(o)). In failing human hearts RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+-induced activation. PMID:11273716

  12. Electron-conformational transformations govern the temperature dependence of the cardiac ryanodine receptor gating

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    Moskvin, A. S.; Iaparov, B. I.; Ryvkin, A. M.; Solovyova, O. E.; Markhasin, V. S.

    2015-07-01

    Temperature influences many aspects of cardiac excitation-contraction coupling, in particular, hypothermia increases the open probability ( P open) of cardiac sarcoplasmic reticulum (SR) Ca2+-release channels (ryanodine-sensitive RyR channels) rising the SR Ca2+ load in mammalian myocytes. However, to the best of our knowledge, no theoretical models are available for that effect. Traditional Markov chain models do not provide a reasonable molecular mechanistic insight on the origin of the temperature effects. Here in the paper we address a simple physically clear electron-conformational model to describe the RyR gating and argue that a synergetic effect of external thermal fluctuation forces (Gaussian-Markovian noise) and internal friction via the temperature stimulation/suppression of the open-close RyR tunneling probability can be considered as a main contributor to temperature effects on the RyR gating. Results of the computer modeling allowed us to successfully reproduce all the temperature effects observed for an isolated RyR gating in vitro under reducing the temperature: increase in P open and mean open time without any significant effect on mean closed

  13. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

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    Rannou, F; Sainte-Beuve, C; Oliviero, P; Do, E; Trouvé, P; Charlemagne, D

    1995-05-01

    The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved. PMID:7473781

  14. Primary structure and properties of helothermine, a peptide toxin that blocks ryanodine receptors.

    OpenAIRE

    Morrissette, J; Krätzschmar, J.; Haendler, B; el-Hayek, R; Mochca-Morales, J; Martin, B M; Patel, J.R.; Moss, R.L.; Schleuning, W. D.; Coronado, R

    1995-01-01

    Helothermine, a protein from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to inhibit [3H]ryanodine binding to cardiac and skeletal sarcoplasmic reticulum, to block cardiac and skeletal ryanodine receptor channels incorporated into planar bilayers, and to block Ca(2+)-induced Ca2+ release triggered by photolysis of nitr-5 in saponin-permeabilized trabeculae from rat ventricle. Cloning of the helothermine cDNA revealed that the protein is composed of 223 amino...

  15. DEFECTIVE REGULATION OF THE RYANODINE RECEPTOR INDUCES HYPERTROPHY IN CARDIOMYOCYTES

    OpenAIRE

    Hamada, Tomoyo; Gangopadhyay, Jaya P.; Mandl, Adel; Erhardt, Peter; Ikemoto, Noriaki

    2009-01-01

    Recent studies on cardiac hypertrophy animal model suggest that inter-domain interactions within the ryanodine receptor (RyR2) become defective concomitant with the development of hypertrophy (e.g. destabilization of the interaction between N-terminal and central domains of RyR2; Circulation 111, 3400–3410, 2005). To determine if destabilization of the inter-domain interaction in fact causes hypertrophy, we introduced DPc10 (a peptide corresponding to the G2460-P2495 region of RyR2, which is ...

  16. 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

  17. Targeting ryanodine receptors for anti-arrhythmic therapy

    Institute of Scientific and Technical Information of China (English)

    Mark D McCAULEY; Xander H T WEHRENS

    2011-01-01

    Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca2+) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca2+ release has been linked to arrhythmogenesis in both the inherited arrhythmia synSeveral classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca2+ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.

  18. Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy

    Science.gov (United States)

    Pedrozo, Zully; Torrealba, Natalia; Fernández, Carolina; Gatica, Damian; Toro, Barbra; Quiroga, Clara; Rodriguez, Andrea E.; Sanchez, Gina; Gillette, Thomas G.; Hill, Joseph A.; Donoso, Paulina; Lavandero, Sergio

    2013-01-01

    Time for primary review: 15 days Aims Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ. These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit autophagy result in Danon disease characterized by hypertrophic cardiomyopathy. The ryanodine receptor type 2 (RyR2) plays a key role in cardiomyocyte excitation–contraction and its dysfunction can lead to cardiac failure. Whether RyR2 is degraded by CMA is unknown. Methods and results To induce CMA, cultured neonatal rat cardiomyocytes were treated with geldanamycin (GA) to promote protein degradation through this pathway. GA increased LAMP-2A levels together with its redistribution and colocalization with Hsc70 in the perinuclear region, changes indicative of CMA activation. The inhibition of lysosomes but not proteasomes prevented the loss of RyR2. The recovery of RyR2 content after incubation with GA by siRNA targeting LAMP-2A suggests that RyR2 is degraded via CMA. In silico analysis also revealed that the RyR2 sequence harbours six KFERQ motifs which are required for the recognition Hsc70 and its degradation via CMA. Our data suggest that presenilins are involved in RyR2 degradation by CMA. Conclusion These findings are consistent with a model in which oxidative damage of the RyR2 targets it for turnover by presenilins and CMA, which could lead to removal of damaged or leaky RyR2 channels. PMID:23404999

  19. The mitochondrial ryanodine receptor in rat heart: a pharmaco-kinetic profile.

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    Altschafl, Beth A; Beutner, Gisela; Sharma, Virendra K; Sheu, Shey-Shing; Valdivia, Héctor H

    2007-07-01

    A protein discovered within inner mitochondrial membranes (IMM), designated as the mitochondrial ryanodine receptor (mRyR), has been recognized recently as a modulator of Ca(2+) fluxes in mitochondria. The present study provides fundamental pharmacological and electrophysiological properties of this mRyR. Rat cardiac IMM fused to lipid bilayers revealed the presence of a mitochondrial channel with gating characteristics similar to those of classical sarcoplasmic reticulum RyR (SR-RyR), but a variety of other mitochondrial channels obstructed clean recordings. Mitochondrial vesicles were thus solubilized and subjected to sucrose sedimentation to obtain mRyR-enriched fractions. Reconstitution of sucrose-purified fractions into lipid bilayers yielded Cs(+)-conducting, Ca(2+)-sensitive, large conductance (500-800 pS) channels with signature properties of SR-RyRs. Cytosolic Ca(2+) increased the bursting frequency and mean open time of the channel. Micromolar concentrations of ryanodine induced the appearance of subconductance states or inhibited channel activity altogether, while Imperatoxin A (IpTx(a)), a specific activator of RyRs, reversibly induced the appearance of distinct subconductance states. Remarkably, the cardiac mRyR displayed a Ca(2+) dependence of [(3)H]ryanodine binding curve similar to skeletal RyR (RyR1), not cardiac RyR (RyR2). Overall, the mRyR displayed elemental attributes that are present in single channel lipid bilayer recordings of SR-RyRs, although some exquisite differences were also noted. These results therefore provide the first direct evidence that a unique RyR occurs in mitochondrial membranes. PMID:17499575

  20. Ryanodine modification of cardiac muscle responses to potassium-free solutions. Evidence for inhibition of sarcoplasmic reticulum calcium release

    OpenAIRE

    1983-01-01

    To test whether ryanodine blocks the release of calcium from the sarcoplasmic reticulum in cardiac muscle, we examined its effects on the aftercontractions and transient depolarizations or transient inward currents developed by guinea pig papillary muscles and voltage-clamped calf cardiac Purkinje fibers in potassium-free solutions. Ryanodine (0.1-1.0 microM) abolished or prevented aftercontractions and transient depolarizations by the papillary muscles without affecting any of the other sequ...

  1. Fluorescent Probes for Insect Ryanodine Receptors: Candidate Anthranilic Diamides

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2014-04-01

    Full Text Available Diamide insecticides with high efficacy against pests and good environmental safety are broadly applied in crop protection. They act at a poorly-defined site in the very complex ryanodine (Ry receptor (RyR potentially accessible to a fluorescent probe. Two N-propynyl analogs of the major anthranilic diamide insecticides chlorantraniliprole (Chlo and cyantraniliprole (Cyan were accordingly synthesized and converted into two fluorescent ligands by click reaction coupling with 3-azido-7-hydroxy-2H-chromen-2-one. The new diamide analogs and fluorescent ligands were shown to be nearly as potent as Chlo and Cyan in inhibition of [3H]Chlo binding and stimulation of [3H]Ry binding in house fly thoracic muscle RyR. Although the newly synthesized compounds had only moderate activity in insect larvicidal activity assays, their high in vitro potency in a validated insect RyR binding assay encourages further development of fluorescent probes for insect RyRs.

  2. Role of the dysfunctional ryanodine receptor - Na(+)-Ca(2+)exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

    Science.gov (United States)

    Acsai, Károly; Ördög, Balázs; Varró, András; Nánási, Péter P

    2016-05-15

    Abnormal Ca(2+)homeostasis is often associated with chronic cardiovascular diseases, such as hypertension, heart failure or cardiac arrhythmias, and typically contributes to the basic ethiology of the disease. Pharmacological targeting of cardiac Ca(2+)handling has great therapeutic potential offering invaluable options for the prevention, slowing down the progression or suppression of the harmful outcomes like life threatening cardiac arrhythmias. In this review we outline the existing knowledge on the involvement of malfunction of the ryanodine receptor and the Na(+)-Ca(2+)exchanger in disturbances of Ca(2+)homeostasis and discuss important proof of concept pharmacological studies targeting these mechanisms in context of hypertension, heart failure, atrial fibrillation and ventricular arrhythmias. We emphasize the promising results of preclinical studies underpinning the potential benefits of the therapeutic strategies based on ryanodine receptor or Na(+)-Ca(2+)exchanger inhibition. PMID:26970182

  3. Ryanodine receptors as pharmacological targets for heart disease

    Institute of Scientific and Technical Information of China (English)

    Marco SANTONASTASI; Xander H T WEHRENS

    2007-01-01

    Calcium release from intracellular stores plays an important role in the regulationof muscle contraction and electrical signals that determine the heart rhythm. Theryanodine receptor (RyR) is the major calcium (Ca2+) release channel required forexcitation-contraction coupling in the heart. Recent studies have demonstratedthat RyR are macromolecular complexes comprising of 4 pore-forming channelsubunits, each of which is associated with regulatory subunits. Clinical andexperimental studies over the past 5 years have provided compelling evidencethat intracellular Ca2+release channels play a pivotal role in the development ofcardiac arrhythmias and heart failure. Changes in the channel regulation andsubunit composition are believed to cause diastolic calcium leakage from thesarcoplasmic reticulum, which could trigger arrhythmias and weaken cardiaccontractility. Therefore, cardiac RyR have emerged as potential therapeutic tar-gets for the treatment of heart disease. Consequently, there is a strong desire toidentify and/or develop novel pharmacological agents that may target these Ca2+signaling pathways. Pharmacological agents known to modulate RyR in the heart,and their potential application towards the treatment of heart disease are dis-cussed in this review.

  4. Ryanodine receptors are involved in nuclear calcium oscillation in primary pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ji [Urological Surgery Research Institute, Southwest Hospital, Third Military Medical University, Chongqing (China); National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing (China); Chen, Zheng [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing (China); Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI (United States); Yin, Wenxuan; Miao, Lin [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing (China); Zhou, Zhansong, E-mail: Zhouzhansong@sohu.com [Urological Surgery Research Institute, Southwest Hospital, Third Military Medical University, Chongqing (China); Ji, Guangju, E-mail: Gj28@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing (China)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer We found that RyRs are expressed on the nuclear envelope in single primary pancreatic {beta}-cells and isolated nuclei. Black-Right-Pointing-Pointer We showed that the pattern of glucose-induced Ca{sup 2+} oscillation in the nucleus and cytosol was similar. Black-Right-Pointing-Pointer Our results demonstrate that ryanodine-sensitive Ca{sup 2+} stores exist and have function in the pancreatic {beta}-cell nucleus. -- Abstract: Ryanodine receptors (RyRs) are mainly located on the endoplasmic reticulum (ER) and play an important role in regulating glucose-induced cytosolic Ca{sup 2+} oscillation in pancreatic {beta}-cells. However, subcellular locations and functions of RyRs on other cell organelles such as nuclear envelope are not well understood. In order to investigate the role of RyRs in nuclear Ca{sup 2+} oscillation we designed and conducted experiments in intact primary pancreatic {beta}-cells. Immunocytochemistry was used to examine the expression of RYRs on the nuclear envelope. Confocal microscopy was used to evaluate the function of RYRs on the nuclear envelope. We found that RyRs are expressed on the nuclear envelope in single primary pancreatic {beta}-cells and isolated nuclei. Laser scanning confocal microscopy studies indicated that application of glucose to the cells co-incubated with Ca{sup 2+} indicator Fluo-4 AM and cell-permeable nuclear indicator Hoechst 33342 resulted in nuclear Ca{sup 2+} oscillation. The pattern of glucose-induced Ca{sup 2+} oscillation in the nucleus and cytosol was similar. The reduction of Ca{sup 2+} oscillation amplitude by ryanodine was much greater in the nucleus though both the cytosol and the nucleus Ca{sup 2+} amplitude decreased by ryanodine. Our results suggest that functional ryanodine receptors not only exist in endoplasmic reticulum but are also expressed in nuclear envelope of pancreatic {beta}-cells.

  5. Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

    OpenAIRE

    Adasme, Tatiana; Haeger, Paola; Paula-Lima, Andrea C.; Espinoza, Italo; Casas-Alarcón, M. Mercedes; Carrasco, M. Angélica; Hidalgo, Cecilia

    2011-01-01

    Ryanodine receptors (RyR) amplify activity-dependent calcium influx via calcium-induced calcium release. Calcium signals trigger postsynaptic pathways in hippocampal neurons that underlie synaptic plasticity, learning, and memory. Recent evidence supports a role of the RyR2 and RyR3 isoforms in these processes. Along with calcium signals, brain-derived neurotrophic factor (BDNF) is a key signaling molecule for hippocampal synaptic plasticity and spatial memory. Upon binding to specific TrkB r...

  6. Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development

    Directory of Open Access Journals (Sweden)

    Wu Houdini HT

    2011-12-01

    Full Text Available Abstract Background Calcium signals ([Ca2+]i direct many aspects of embryo development but their regulation is not well characterised. Ryanodine receptors (RyRs are a family of intracellular Ca2+ release channels that control the flux of Ca2+ from internal stores into the cytosol. RyRs are primarily known for their role in excitation-contraction coupling in adult striated muscle and ryr gene mutations are implicated in several human diseases. Current evidence suggests that RyRs do not have a major role to play prior to organogenesis but regulate tissue differentiation. Findings The sequences of the five zebrafish ryr genes were confirmed, their evolutionary relationship established and the primary sequences compared to other vertebrates, including humans. RyRs are differentially expressed in slow (ryr1a, fast (ryr3 and both types (ryr1b of developing skeletal muscle. There are two ryr2 genes (ryr2a and ryr2b which are expressed exclusively in developing CNS and cardiac tissue, respectively. In addition, ryr3 and ryr2a mRNA is detectable in the initial stages of development, prior to embryonic axis formation. Conclusions Our work reveals that zebrafish ryr genes are differentially expressed throughout the developing embryo from cleavage onwards. The data suggests that RyR-regulated Ca2+ signals are associated with several aspects of embryonic development, from organogenesis through to the differentiation of the musculoskeletal, cardiovascular and nervous system. These studies will facilitate further work to explore the developmental function of RyRs in each of these tissue types.

  7. Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

    Directory of Open Access Journals (Sweden)

    V.A. Vizotto

    2007-01-01

    Full Text Available We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2, phospholamban (PLB, and ryanodine channel (RYR2 mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 ± 0.48 vs food-restricted group = 4.84 ± 0.33, P < 0.01. The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 ± 0.44 vs food-restricted group = 7.96 ± 0.45, and control = 1.52 ± 0.06 vs food-restricted group = 1.53 ± 0.10, respectively. Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

  8. Structure-function relationships of peptides forming the calcin family of ryanodine receptor ligands.

    Science.gov (United States)

    Xiao, Liang; Gurrola, Georgina B; Zhang, Jing; Valdivia, Carmen R; SanMartin, Mario; Zamudio, Fernando Z; Zhang, Liming; Possani, Lourival D; Valdivia, Héctor H

    2016-05-01

    Calcins are a novel family of scorpion peptides that bind with high affinity to ryanodine receptors (RyRs) and increase their activity by inducing subconductance states. Here, we provide a comprehensive analysis of the structure-function relationships of the eight calcins known to date, based on their primary sequence, three-dimensional modeling, and functional effects on skeletal RyRs (RyR1). Primary sequence alignment and evolutionary analysis show high similarity among all calcins (≥78.8% identity). Other common characteristics include an inhibitor cysteine knot (ICK) motif stabilized by three pairs of disulfide bridges and a dipole moment (DM) formed by positively charged residues clustering on one side of the molecule and neutral and negatively charged residues segregating on the opposite side. [(3)H]Ryanodine binding assays, used as an index of the open probability of RyRs, reveal that all eight calcins activate RyR1 dose-dependently with Kd values spanning approximately three orders of magnitude and in the following rank order: opicalcin1 > opicalcin2 > vejocalcin > hemicalcin > imperacalcin > hadrucalcin > maurocalcin > urocalcin. All calcins significantly augment the bell-shaped [Ca(2+)]-[(3)H]ryanodine binding curve with variable effects on the affinity constants for Ca(2+) activation and inactivation. In single channel recordings, calcins induce the appearance of a subconductance state in RyR1 that has a unique fractional value (∼20% to ∼60% of the full conductance state) but bears no relationship to binding affinity, DM, or capacity to stimulate Ca(2+) release. Except for urocalcin, all calcins at 100 nM concentration stimulate Ca(2+) release and deplete Ca(2+) load from skeletal sarcoplasmic reticulum. The natural variation within the calcin family of peptides offers a diversified set of high-affinity ligands with the capacity to modulate RyRs with high dynamic range and potency. PMID:27114612

  9. Radioligand assay of cardiac calcium release channel and its application in SHR

    International Nuclear Information System (INIS)

    Purpose: To establish the best condition in assaying the calcium release channel (ryanodine receptor) in cardiac sarcoplasmic reticulum (CSR), and analyse the CSR ryanodine receptor in spantanous hypertensive rat (SHR). Methods: 3H-ryanodine was used as a radioligand to analyse the binding in Sprague Dawley rat cardiac homogenate in following conditions: varied protein concentrations, different free calcium concentrations, different incubation time. The effect of sarcoplasmic reticulum purifying process and ryanodine competitive binding were also studied. Using these best conditions, SHR and control group (WKY) CSR ryanodine receptor were studied. Results: 1) There was a positive linear correlation between 3H-ryanodine binding and the homogenate protein concentration. 2) When the free calcium concentration was 30 μmol/L∼1 mmol/L, the 3H-ryanodine binding reached the maximum. While the free calcium concentration was lower than 1 μmol/L, there was no 3H-ryanodine binding. 3) The 3H-ryanodine binding kept increasing during incubation, from 0 to 60 min, and equilibrium reached by 90 min. 4) The ryanodine specifically inhibited 3H-ryanodine binding in cardiac homogenate. 5) During the sarcoplasmic reticulum purifying process, the 3H-ryanodine binding in a unit amount of cardiac homogenate decreased with the centrifugal force and times applied in centrifugation. 6) SHR and WKY CSR ryanodine receptor saturation curve and Scatchard analysis showed this method produced a very high level of specific binding, up to 45 nmol/L ryanodine, which inferred a single class of binding sites. The Bmax value of CSR ryanodine receptor in SHR left ventricle was significantly higher than that in WKY (P3H-ryanodine can be used as a radioligand to analyse the calcium release channel in cardiac homogenate, and ryanodine receptor may play an important role in hypertensive left ventricular remodeling process

  10. Expression of Dihydropyridine and Ryanodine Receptors in Type IIA Fibers of Rat Skeletal Muscle

    International Nuclear Information System (INIS)

    In this study, the fiber type specificity of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs) in different rat limb muscles was investigated. Western blot and histochemical analyses provided for the first time evidence that the expression of both receptors correlates to a specific myosin heavy chain (MHC) composition. We observed a significant (p=0.01) correlation between DHP as well as Ry receptor density and the expression of MHC IIa (correlation factor r=0.674 and r=0.645, respectively) in one slow-twitch, postural muscle (m. soleus), one mixed, fast-twitch muscle (m. gastrocnemius) and two fast-twitch muscles (m. rectus femoris, m. extensor digitorum longus). The highest DHP and Ry receptor density was found in the white part of m. rectus femoris (0.058±0.0060 and 0.057±0.0158 ODu, respectively). As expected, the highest relative percentage of MHC IIa was also found in the white part of m. rectus femoris (70.0±7.77%). Furthermore, histochemical experiments revealed that the IIA fibers stained most strongly for the fluorophore-conjugated receptor blockers. Our data clearly suggest that the expression of DHPRs and RyRs follows a fiber type-specific pattern, indicating an important role for these proteins in the maintenance of an effective Ca2+ cycle in the fast contracting fiber type IIA

  11. Atomic force microscopy study of the rabbit skeletal muscle ryanodine receptors in different functional states

    Institute of Scientific and Technical Information of China (English)

    魏青青; 程晓阳; 陈克樱; 胡钧; 李民乾; 朱培闳

    2002-01-01

    Atomic force microscope was applied to investigate the effect of extrinsic phospholipid on the structure of rabbit skeletal muscle ryanodine receptor/calcium release channel (RyR1). In addition, in the presence of extrinsic phospholipid, the height and elasticity of the RyR1s in different functional states were also measured. The results indicate: (i) most of the RyR1s showed a normal structure only in the presence of extrinsic phospholipid; (ii) treatment of the RyR1s with AMP and Ca2+ together could increase their Young's Modulus but not change their apparent height; (iii) no detectable change in either height or Young's Modulus of the RyR1s appeared, if the RyR1s were treated with other activators or inhibitors.

  12. Redox-sensitive stimulation of type-1 ryanodine receptors by the scorpion toxin maurocalcine. : Redox-sensitive RyR stimulation by Maurocalcine

    OpenAIRE

    Ronjat, Michel; Finkelstein, José Pablo; Llanos, Paola; Montecinos, Luis; Bichraoui, Hicham; De Waard, Michel; Hidalgo, Cecilia; Bull, Ricardo

    2013-01-01

    The scorpion toxin maurocalcine acts as a high affinity agonist of the type-1 ryanodine receptor expressed in skeletal muscle. Here, we investigated the effects of the reducing agent dithiothreitol or the oxidizing reagent thimerosal on type-1 ryanodine receptor stimulation by maurocalcine. Maurocalcine addition to sarcoplasmic reticulum vesicles actively loaded with calcium elicited Ca(2+) release from native vesicles and from vesicles pre-incubated with dithiothreitol; thimerosal addition t...

  13. Complex formation between calsequestrin and the ryanodine receptor in fast- and slow-twitch rabbit skeletal muscle.

    Science.gov (United States)

    Murray, B E; Ohlendieck, K

    1998-06-16

    Linkage between the high-capacity Ca2+-binding protein calsequestrin and the ryanodine receptor is proposed to be essential for proper Ca2+-release during skeletal muscle excitation-contraction coupling. However, no direct biochemical evidence exists showing a connection between these high-molecular-mass complexes in native skeletal muscle membranes. Here, using immunoblot analysis of chemically crosslinked membrane vesicles enriched in triad junctions, we have demonstrated that a very close neighborhood relationship exists between calsequestrin and the ryanodine receptor in both main fiber types. Hence, the luminal Ca2+-reservoir complex appears to be directly coupled to the membrane Ca2+-release complex and oligomerization seems to be of functional importance. PMID:9662440

  14. Molecular cloning, characterisation and mRNA expression of the ryanodine receptor from the peach-potato aphid, Myzus persicae

    OpenAIRE

    Troczka, B.J.; Williams, A J; Bass, C; Williamson, M.S.; Field, L.M.; Davies, T.G.E.

    2015-01-01

    The peach potato aphid, Myzus persicae, is one of the most important agricultural pests of temperate climates. It is mainly controlled through the judicious application of insecticides; however, over time, aphids have developed resistance to many insecticidal classes. The recent introduction of synthetic diamide insecticides, with a novel mode of action, potentially offers new tools to control aphid populations. These diamides act on the ryanodine receptor (RyR), a large endoplasmic calcium r...

  15. Selective inhibition of phosphodiesterase 1 relaxes urinary bladder smooth muscle: role for ryanodine receptor-mediated BK channel activation

    OpenAIRE

    Xin, Wenkuan; Soder, Rupal P; Cheng, Qiuping; Eric S. Rovner; Petkov, Georgi V.

    2012-01-01

    The large conductance voltage- and Ca2+-activated K+ (BK) channel is a major regulator of detrusor smooth muscle (DSM) excitability and contractility. Recently, we showed that nonselective phosphodiesterase (PDE) inhibition reduces guinea pig DSM excitability and contractility by increasing BK channel activity. Here, we investigated how DSM excitability and contractility changes upon selective inhibition of PDE type 1 (PDE1) and the underlying cellular mechanism involving ryanodine receptors ...

  16. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia. PMID:27262216

  17. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    International Nuclear Information System (INIS)

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion–reaction equations presented by Izu et al (2001 Biophys. J. 80 103–20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF

  18. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    Science.gov (United States)

    Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

    2010-06-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF.

  19. Disease Mutations in the Ryanodine Receptor Central Region: Crystal Structures of a Phosphorylation Hot Spot Domain

    Energy Technology Data Exchange (ETDEWEB)

    Yuchi, Zhiguang; Lau, Kelvin; Van Petegem, Filip (UBC)

    2015-02-09

    Ryanodine Receptors (RyRs) are huge Ca{sup 2+} release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain salt bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.

  20. Identification of ryanodine receptor isoforms in prostate DU-145, LNCaP, and PWR-1E cells.

    Science.gov (United States)

    Kobylewski, Sarah E; Henderson, Kimberly A; Eckhert, Curtis D

    2012-08-24

    The ryanodine receptor (RyR) is a large, intracellular calcium (Ca(2+)) channel that is associated with several accessory proteins and is an important component of a cell's ability to respond to changes in the environment. Three isoforms of the RyR exist and are well documented for skeletal and cardiac muscle and the brain, but the isoforms in non-excitable cells are poorly understood. The aggressiveness of breast cancers in women has been positively correlated with the expression of the RyR in breast tumor tissue, but it is unknown if this is limited to specific isoforms. Identification and characterization of RyRs in cancer models is important in understanding the role of the RyR channel complex in cancer and as a potential therapeutic target. The objective of this report was to identify the RyR isoforms expressed in widely used prostate cancer cell lines, DU-145 and LNCaP, and the non-tumorigenic prostate cell line, PWR-1E. Oligonucleotide primers specific for each isoform were used in semi-quantitative and real-time PCR to determine the identification and expression levels of the RyR isoforms. RyR1 was expressed in the highest amount in DU-145 tumor cells, expression was 0.48-fold in the non-tumor cell line PWR-1E compared to DU-145 cells, and no expression was observed in LNCaP tumor cells. DU-145 cells had the lowest expression of RyR2. The expression was 26- and 15-fold higher in LNCaP and PWR-1E cells, respectively. RyR3 expression was not observed in any of the cell lines. All cell types released Ca(2+) in response to caffeine showing they had functional RyRs. Total cellular RyR-associated Ca(2+) release is determined by both the number of activated RyRs and its accessory proteins which modulate the receptor. Our results suggest that the correlation between the expression of the RyR and tumor aggression is not related to specific RyR isoforms, but may be related to the activity and number of receptors. PMID:22846571

  1. FRET-based localization of fluorescent protein insertions within the ryanodine receptor type 1.

    Directory of Open Access Journals (Sweden)

    Shweta A Raina

    Full Text Available Fluorescent protein (FP insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET measurements were used to localize green fluorescent protein (GFP insertions within the ryanodine receptor type 1 (RyR1, a large intracellular Ca(2+ release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length His-tagged GFP-RyR1 fusion constructs were created, expressed in human embryonic kidney (HEK-293T cells and then complexed with Cy3NTA, a His-tag specific FRET acceptor. FRET efficiency values measured from each GFP donor to Cy3NTA bound to each His tag acceptor site were converted into intermolecular distances and the positions of each inserted GFP were then triangulated relative to a previously published X-ray crystal structure of a 559 amino acid RyR1 fragment. We observed that the chromophoric centers of fluorescent proteins inserted into RyR1 can be located as far as 45 Å from their insertion sites and that the fused proteins can also be located in internal cavities within RyR1. These findings should prove useful in interpreting structural results obtained in cryo EM maps using fusions of small fluorescent proteins. More accurate point-to-point distance information may be obtained using complementary orthogonal labeling systems that rely on fluorescent probes that bind directly to amino acid side chains.

  2. The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Liu, Jie; Supnet, Charlene; Sun, Suya; Zhang, Hua; Good, Levi; Popugaeva, Elena; Bezprozvanny, Ilya

    2014-01-01

    Dysregulated endoplasmic reticulum (ER) calcium (Ca(2+)) signaling is reported to play an important role in Alzheimer disease (AD) pathogenesis. The role of ER Ca(2+) release channels, the ryanodine receptors (RyanRs), has been extensivelys tudied in AD models and RyanR expression and activity are upregulated in the brains of various familial AD (FAD) models.The objective of this study was to utilize a genetic approach to evaluate the importance of RyanR type 3 (RyanR3) in the context of AD pathology.The expression of RyanR3 was also elevated in hippocampus of APPPS1 mice (Thy1-APPKM670/671NL, Thy1-PS1L166P).In young (≤ 3 mo) APPPS1 mice, the deletion of RyanR3 increased hippocampal neuronal network excitability and accelerated AD pathology, leading to mushroom spine loss and increased amyloid accumulation. In contrast, deletion of RyanR3 in older APPPS1 mice (≥ 6 mo) rescued network excitability and mushroom spine loss, reduced amyloid plaque load and reduced spontaneous seizure occurrence.Our data suggests a dual role for RyanR3 in AD pathology. In young AD neurons, RyanR3 protects AD neurons from synaptic and network dysfunction. In older AD neurons, increased RyanR3 activity contributes to pathology. These results imply that blockade of RyanR3 may be beneficial for those in the later stages of the disease, but RyanR activators may be beneficial when used prior to disease onset or in its initial stages. Caffeine is an activator of RyanRs and our results may help to explain a complex epidemiological connection between coffee consumption in mid-life and risk of AD development in old age. PMID:24476841

  3. Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells.

    Science.gov (United States)

    Stern, Michael D; Maltseva, Larissa A; Juhaszova, Magdalena; Sollott, Steven J; Lakatta, Edward G; Maltsev, Victor A

    2014-05-01

    The sinoatrial node, whose cells (sinoatrial node cells [SANCs]) generate rhythmic action potentials, is the primary pacemaker of the heart. During diastole, calcium released from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) interacts with membrane currents to control the rate of the heartbeat. This "calcium clock" takes the form of stochastic, partially periodic, localized calcium release (LCR) events that propagate, wave-like, for limited distances. The detailed mechanisms controlling the calcium clock are not understood. We constructed a computational model of SANCs, including three-dimensional diffusion and buffering of calcium in the cytosol and SR; explicit, stochastic gating of individual RyRs and L-type calcium channels; and a full complement of voltage- and calcium-dependent membrane currents. We did not include an anatomical submembrane space or inactivation of RyRs, the two heuristic components that have been used in prior models but are not observed experimentally. When RyRs were distributed in discrete clusters separated by >1 µm, only isolated sparks were produced in this model and LCR events did not form. However, immunofluorescent staining of SANCs for RyR revealed the presence of bridging RyR groups between large clusters, forming an irregular network. Incorporation of this architecture into the model led to the generation of propagating LCR events. Partial periodicity emerged from the interaction of LCR events, as observed experimentally. This calcium clock becomes entrained with membrane currents to accelerate the beating rate, which therefore was controlled by the activity of the SERCA pump, RyR sensitivity, and L-type current amplitude, all of which are targets of β-adrenergic-mediated phosphorylation. Unexpectedly, simulations revealed the existence of a pathological mode at high RyR sensitivity to calcium, in which the calcium clock loses synchronization with the membrane, resulting in a paradoxical decrease in beating

  4. Synthesis, Larvicidal Activities and Antifungal Activities of Novel Chlorantraniliprole Derivatives and Their Target in the Ryanodine Receptor

    Directory of Open Access Journals (Sweden)

    Qichao Chen

    2015-03-01

    Full Text Available In order to identify novel chlorantraniliprole derivatives as potential insecticides or fungicides, 25 analogues of chlorantraniliprole were synthesized. The insecticidal activities against oriental armyworm and the antifungal activities against five typical fungi of these derivatives were tested. Compounds 2u, 2x and 2y exhibited good activities against oriental armyworm, especially compounds 2u and 2x which showed higher larvicidal activities than indoxacarb. Moreover, all of the tested compounds exhibited activities against five typical fungi. The Ki values of all synthesized compounds were calculated using AutoDock4. The relationship between the Ki values and the results of insecticidal activities against oriental armyworm further indicated that the membrane-spanning domain protein of the ryanodine receptor might contain chlorantraniliprole binding sites.

  5. RNAi suppression of the ryanodine receptor gene results in decreased susceptibility to chlorantraniliprole in Colorado potato beetle Leptinotarsa decemlineata.

    Science.gov (United States)

    Wan, Pin-Jun; Guo, Wei-Yan; Yang, Yao; Lü, Feng-Gong; Lu, Wei-Ping; Li, Guo-Qing

    2014-04-01

    Leptinotarsadecemlineata is the most important pest in potato and causes serious yield loss each year. Chlorantraniliprole acts on insect ryanodine receptors (RyRs) and is among the most active compounds against L. decemlineata. Here we cloned and characterized a 15,792-bp full-length LdRyR cDNA that encoded a 5128-amino acid protein. LdRyR shares 85-92% amino acid similarities with other insect RyR homologues, and 59-61% similarities with those from Caenorhabditis elegans and Homo sapiens. All hallmarks of the RyR proteins are conserved in LdRyR. LdRyR has a MIR domain, two RIH domains, three SPRY domains, four copies of RyR domain and a RIH-associated domain in the N-terminus, and it possesses two consensus calcium ion-binding EF-hand motifs and six predicted transmembrane helices in the C-terminus. Temporal, spatial and tissue-specific expression patterns of LdRyR were evaluated. LdRyR expression level was increased constantly from egg to wandering stages, dropped in pupal stage and was increased again in the adult stage. It was widely expressed in the head, thorax and abdomen of day 3 fourth-instar larvae. Moreover, it was ubiquitously expressed in all inspected tissues including epidermis, foregut, midgut, ileum, rectum, fat body, ventral ganglia and Malpighian tubules in day 3 fourth-instar larvae. Dietary introduction of double-stranded RNA of LdRyR significantly reduced the mRNA levels of the target gene in the larvae and adults, respectively, and significantly decreased chlorantraniliprole-induced mortalities. Thus, our results suggested that LdRyR encoded a functional ryanodine receptor in L. decemlineata. PMID:24607641

  6. Homeostatic and stimulus-induced coupling of the L-type Ca2+ channel to the ryanodine receptor in the hippocampal neuron in slices

    OpenAIRE

    Berrout, Jonathan; Isokawa, Masako

    2009-01-01

    Activity-dependent increase in cytosolic calcium ([Ca2+]i) is a prerequisite for many neuronal functions. We previously reported a strong direct depolarization, independent of glutamate receptors, effectively caused a release of Ca2+ from ryanodine sensitive stores and induced the synthesis of endogenous cannabinoids (eCBs) and eCB-mediated responses. However, the cellular mechanism that initiated the depolarization-induced Ca2+ release is not completely understood. In the present study, we o...

  7. Molecular cloning, characterisation and mRNA expression of the ryanodine receptor from the peach-potato aphid, Myzus persicae.

    Science.gov (United States)

    Troczka, B J; Williams, A J; Bass, C; Williamson, M S; Field, L M; Davies, T G E

    2015-02-10

    The peach potato aphid, Myzus persicae, is one of the most important agricultural pests of temperate climates. It is mainly controlled through the judicious application of insecticides; however, over time, aphids have developed resistance to many insecticidal classes. The recent introduction of synthetic diamide insecticides, with a novel mode of action, potentially offers new tools to control aphid populations. These diamides act on the ryanodine receptor (RyR), a large endoplasmic calcium release channel. In this study we have cloned cDNAs encoding the complete open reading frame of the RyR from M. persicae. The open reading frame is 15,306 base pairs long and encodes a protein of 5101 amino acids. The aphid RyR shares many of the features of other insect and vertebrate RyRs, including a highly conserved transmembrane region. However, unlike the other RyRs characterised to date, the M. persicae channel does not display alternative splicing at any stage of its developmental cycle, so it cannot generate functional variants of the channel. PMID:25447916

  8. A structural model of the pore-forming region of the skeletal muscle ryanodine receptor (RyR1.

    Directory of Open Access Journals (Sweden)

    Srinivas Ramachandran

    2009-04-01

    Full Text Available Ryanodine receptors (RyRs are ion channels that regulate muscle contraction by releasing calcium ions from intracellular stores into the cytoplasm. Mutations in skeletal muscle RyR (RyR1 give rise to congenital diseases such as central core disease. The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level. Here, we report a structural model of the pore-forming region of RyR1. Molecular dynamics simulations show high ion binding to putative pore residues D4899, E4900, D4938, and D4945, which are experimentally known to be critical for channel conductance and selectivity. We also observe preferential localization of Ca(2+ over K(+ in the selectivity filter of RyR1. Simulations of RyR1-D4899Q mutant show a loss of preference to Ca(2+ in the selectivity filter as seen experimentally. Electrophysiological experiments on a central core disease mutant, RyR1-G4898R, show constitutively open channels that conduct K(+ but not Ca(2+. Our simulations with G4898R likewise show a decrease in the preference of Ca(2+ over K(+ in the selectivity filter. Together, the computational and experimental results shed light on ion conductance and selectivity of RyR1 at an atomistic level.

  9. Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein Oligomerization: The Ryanodine Receptor Case Study.

    Science.gov (United States)

    Stanczyk, Paulina J; Lai, F Anthony; Zissimopoulos, Spyros

    2016-01-01

    Oligomerization is often a structural requirement for proteins to accomplish their specific cellular function. For instance, tetramerization of the ryanodine receptor (RyR) is necessary for the formation of a functional Ca(2+) release channel pore. Here, we describe detailed protocols for the assessment of protein self-association, including yeast two-hybrid (Y2H), co-immunoprecipitation (co-IP) and chemical cross-linking assays. In the Y2H system, protein self-interaction is detected by β-galactosidase assay in yeast co-expressing GAL4 bait and target fusions of the test protein. Protein self-interaction is further assessed by co-IP using HA- and cMyc-tagged fusions of the test protein co-expressed in mammalian HEK293 cells. The precise stoichiometry of the protein homo-oligomer is examined by cross-linking and SDS-PAGE analysis following expression in HEK293 cells. Using these different but complementary techniques, we have consistently observed the self-association of the RyR N-terminal domain and demonstrated its intrinsic ability to form tetramers. These methods can be applied to protein-protein interaction and homo-oligomerization studies of other mammalian integral membrane proteins. PMID:27500320

  10. Homeostatic and stimulus-induced coupling of the L-type Ca2+ channel to the ryanodine receptor in the hippocampal neuron in slices

    Science.gov (United States)

    Berrout, Jonathan; Isokawa, Masako

    2009-01-01

    Activity-dependent increase in cytosolic calcium ([Ca2+]i) is a prerequisite for many neuronal functions. We previously reported a strong direct depolarization, independent of glutamate receptors, effectively caused a release of Ca2+ from ryanodine sensitive stores and induced the synthesis of endogenous cannabinoids (eCBs) and eCB-mediated responses. However, the cellular mechanism that initiated the depolarization-induced Ca2+ release is not completely understood. In the present study, we optically recorded [Ca2+]i from CA1 pyramidal neurons in the hippocampal slice and directly monitored miniature Ca2+ activities and depolarization-induced Ca2+ signals in order to determine the source(s) and properties of [Ca2+]i-dynamics that could lead to a release of Ca2+ from the ryanodine receptor. In the absence of depolarizing stimuli, spontaneously-occurring miniature Ca2+ events were detected from a group of hippocampal neurons. This miniature Ca2+ event persisted in the nominal Ca2+-containing artificial cerebrospinal fluid (ACSF), and increased in frequency in response to the bath-application of caffeine and KCl. In contrast, nimodipine, the antagonist of the L-type Ca2+ channel (LTCC), a high concentration of ryanodine, the antagonist of the ryanodine receptor (RyR), and thapsigargin (TG) reduced the occurrence of the miniature Ca2+ events. When a brief puff-application of KCl was given locally to the soma of individual neurons in the presence of glutamate receptor antagonists, these neurons generated a transient increase in the [Ca2+]i in the dendrosomal region. This [Ca2+]i-transient was sensitive to nimodipine, TG, and ryanodine suggesting that the [Ca2+]i-transient was caused primarily by the LTCC-mediated Ca2+-influx and a release of Ca2+ from RyR. We observed little contribution from N-or P/Q-type Ca2+ channels. The coupling between LTCC and RyR was direct and independent of synaptic activities. Immunohistochemical study revealed a cellular localization of LTCC

  11. Molecular cloning, characterization and expression profiling of a ryanodine receptor gene in Asian corn borer, Ostrinia furnacalis (Guenee.

    Directory of Open Access Journals (Sweden)

    Li Cui

    Full Text Available Ryanodine receptor (RyR Ca(2+ release channel is the target of diamide insecticides, which show selective insecticidal activity against lepidopterous insects. To study the molecular mechanisms underlying the species-specific action of diamide insecticides, we have cloned and characterized the entire cDNA sequence of RyR from Ostrinia furnacalis (named as OfRyR. The OfRyR mRNA has an Open Reading Frame of 15324 bp nucleotides and encodes a 5108 amino acid polypeptide that displays 79-97% identity with other insects RyR proteins and shows the greatest identity with Cnaphalocrocis medinalis RyR (97%. Quantitative real-time PCR showed that the OfRyR was expressed at the lowest level in egg and the highest level in adult. The relative expression level of OfRyR in first, third and fifth-instar larva were 1.28, 1.19 and 1.99 times of that in egg. Moreover, two alternative splicing sites were identified in the OfRyR gene. One pair of mutually exclusive exons (a/b were present in the central part of the predicted SPRY domain, and an optional exon (c was located between the third and fourth RyR domains. Diagnostic PCR demonstrated that exons a and b existed in all developmental stages of OfRyR cDNA, but exon c was not detected in the egg cDNA. And the usage frequencies of these exons showed a significant difference between different developmental stages. These results provided the crucial basis for the functional expression of OfRyR and for the discovery of compound with potentially selective insect activtity.

  12. Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise.

    Science.gov (United States)

    Place, Nicolas; Ivarsson, Niklas; Venckunas, Tomas; Neyroud, Daria; Brazaitis, Marius; Cheng, Arthur J; Ochala, Julien; Kamandulis, Sigitas; Girard, Sebastien; Volungevičius, Gintautas; Paužas, Henrikas; Mekideche, Abdelhafid; Kayser, Bengt; Martinez-Redondo, Vicente; Ruas, Jorge L; Bruton, Joseph; Truffert, Andre; Lanner, Johanna T; Skurvydas, Albertas; Westerblad, Håkan

    2015-12-15

    High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT consisting of 30-s bouts of all-out cycling with 4-min rest in between bouts (≤3 min total exercise time). Skeletal muscle biopsies taken 24 h after the HIIT exercise showed an extensive fragmentation of the sarcoplasmic reticulum (SR) Ca(2+) release channel, the ryanodine receptor type 1 (RyR1). The HIIT exercise also caused a prolonged force depression and triggered major changes in the expression of genes related to endurance exercise. Subsequent experiments on elite endurance athletes performing the same HIIT exercise showed no RyR1 fragmentation or prolonged changes in the expression of endurance-related genes. Finally, mechanistic experiments performed on isolated mouse muscles exposed to HIIT-mimicking stimulation showed reactive oxygen/nitrogen species (ROS)-dependent RyR1 fragmentation, calpain activation, increased SR Ca(2+) leak at rest, and depressed force production due to impaired SR Ca(2+) release upon stimulation. In conclusion, HIIT exercise induces a ROS-dependent RyR1 fragmentation in muscles of recreationally active subjects, and the resulting changes in muscle fiber Ca(2+)-handling trigger muscular adaptations. However, the same HIIT exercise does not cause RyR1 fragmentation in muscles of elite endurance athletes, which may explain why HIIT is less effective in this group. PMID:26575622

  13. Voltage-dependent Ca2+ channels, not ryanodine receptors, activate Ca2+-dependent BK potassium channels in human retinal pigment epithelial cells

    OpenAIRE

    Wimmers, Sönke; Halsband, Claire; Seyler, Sebastian; Milenkovic, Vladimir; Strauß, Olaf

    2008-01-01

    Purpose In different tissues the activation of large conductance Ca2+-activated (BK) potassium channels has been shown to be coupled to voltage-gated Ca2+ channels as well as ryanodine receptors. As activation of BK channels leads to hyperpolarization of the cell, these channels provide a negative feedback mechanism for Ca2+-induced functions. Many cellular functions of the retinal pigment epithelium (RPE) are coupled to changes in [Ca2+]i. The aim of this study was to identify which Ca2+-ent...

  14. Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts.

    Science.gov (United States)

    Cooper, Leroy L; Li, Weiyan; Lu, Yichun; Centracchio, Jason; Terentyeva, Radmila; Koren, Gideon; Terentyev, Dmitry

    2013-12-01

    Ageing is associated with a blunted response to sympathetic stimulation and an increased risk of arrhythmia and sudden cardiac death. Aberrant calcium (Ca(2+)) handling is an important contributor to the electrical and contractile dysfunction associated with ageing. Yet, the specific molecular mechanisms underlying abnormal Ca(2+) handling in ageing heart remain poorly understood. In this study, we used ventricular myocytes isolated from young (5-9 months) and old (4-6 years) rabbit hearts to test the hypothesis that changes in Ca(2+) homeostasis are caused by post-translational modification of ryanodine receptors (RyRs) by mitochondria-derived reactive oxygen species (ROS) generated in the ageing heart. Changes in parameters of Ca(2+) handling were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) Ca(2+) dynamics in intact and permeabilized ventricular myocytes using confocal microscopy. We also measured age-related changes in ROS production and mitochondria membrane potential using a ROS-sensitive dye and a mitochondrial voltage-sensitive fluorescent indicator, respectively. In permeablized myocytes, ageing did not change SERCA activity and spark frequency but decreased spark amplitude and SR Ca(2+) load suggesting increased RyR activity. Treatment with the antioxidant dithiothreitol reduced RyR-mediated SR Ca(2+) leak in permeabilized myocytes from old rabbit hearts to the level comparable to young. Moreover, myocytes from old rabbits had more depolarized mitochondria membrane potential and increased rate of ROS production. Under β-adrenergic stimulation, Ca(2+) transient amplitude, SR Ca(2+) load, and latency of pro-arrhythmic spontaneous Ca(2+) waves (SCWs) were decreased while RyR-mediated SR Ca(2+) leak was increased in cardiomyocytes from old rabbits. Additionally, with β-adrenergic stimulation, scavenging of mitochondrial ROS in myocytes from old rabbit hearts restored redox status of RyRs, which reduced SR Ca(2+) leak, ablated most

  15. Involvement of nitric oxide in iodine deficiency-induced microvascular remodeling in the thyroid gland: role of nitric oxide synthase 3 and ryanodine receptors.

    Science.gov (United States)

    Craps, J; Wilvers, C; Joris, V; De Jongh, B; Vanderstraeten, J; Lobysheva, I; Balligand, J-L; Sonveaux, P; Gilon, P; Many, M-C; Gérard, A-C; Colin, I M

    2015-02-01

    Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca(2+)) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca(2+) is involved in this pathway as intracellular Ca(2+) flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes. PMID:25406019

  16. Membrane depolarization increases ryanodine sensitivity to Ca2+ release to the cytosol in L6 skeletal muscle cells: Implications for excitation-contraction coupling.

    Science.gov (United States)

    Pitake, Saumitra; Ochs, Raymond S

    2016-04-01

    The dihydropyridine receptor in the plasma membrane and the ryanodine receptor in the sarcoplasmic reticulum are known to physically interact in the process of excitation-contraction coupling. However, the mechanism for subsequent Ca(2+) release through the ryanodine receptor is unknown. Our lab has previously presented evidence that the dihydropyridine receptor and ryanodine receptor combine as a channel for the entry of Ca(2+) under resting conditions, known as store operated calcium entry. Here, we provide evidence that depolarization during excitation-contraction coupling causes the dihydropyridine receptor to disengage from the ryanodine receptor. The newly freed ryanodine receptor can then transport Ca(2+) from the sarcoplasmic reticulum to the cytosol. Experimentally, this should more greatly expose the ryanodine receptor to exogenous ryanodine. To examine this hypothesis, we titrated L6 skeletal muscle cells with ryanodine in resting and excited (depolarized) states. When L6 muscle cells were depolarized with high potassium or exposed to the dihydropyridine receptor agonist BAYK-8644, known to induce dihydropyridine receptor movement within the membrane, ryanodine sensitivity was enhanced. However, ryanodine sensitivity was unaffected when Ca(2+) was elevated without depolarization by the ryanodine receptor agonist chloromethylcresol, or by increasing Ca(2+) concentration in the media. Ca(2+) entry currents (from the extracellular space) during excitation were strongly inhibited by ryanodine, but Ca(2+) entry currents in the resting state were not. We conclude that excitation releases the ryanodine receptor from occlusion by the dihydropyridine receptor, enabling Ca(2+) release from the ryanodine receptor to the cytosol. PMID:26643865

  17. Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel

    Energy Technology Data Exchange (ETDEWEB)

    Boschek, Curt B; Jones, Terry E; Squier, Thomas C; Bigelow, Diana J

    2007-08-01

    Calmodulin (CaM) regulates calcium release from intracellular stores in skeletal muscle through its association with the ryanodine receptor (RyR1) calcium release channel, where CaM association enhances channel opening at resting calcium levels and its closing at micromolar calcium levels associated with muscle contraction. A high-affinity CaM-binding sequence (RyRp) has been identified in RyR1, which corresponds to a 30-residue sequence (i.e., K3614 – N3643) located within the central portion of the primary sequence. However, it is currently unclear whether the identified CaM-binding sequence a) senses calcium over the physiological range of calcium-concentrations associated with RyR1 regulation or b) plays a structural role unrelated to the calcium-dependent modulation of RyR1 function. Therefore, we have measured the calcium-dependent activation of the individual domains of CaM in association with RyRp and their relationship to the CaM-dependent regulation of RyR1. These measurements utilize an engineered CaM, permitting the site-specific incorporation of N-(1-pyrene) maleimide at either T34C (PyN-CaM) or T110C (PyC-CaM) in the N- and C-domains, respectively. Consistent with prior measurements, we observe a high-affinity association between both apo- and calcium-activated CaM and RyRp. Upon association with RyRp, fluorescence changes in PyN-CaM or PyC-CaM permit the measurement of the calcium-activation of these individual domains. Fluorescence changes upon calcium-activation of PyC-CaM in association with RyRp are indicative of high-affinity calcium-dependent activation of the C-terminal domain of CaM bound to RyRp at resting calcium levels and the activation of the N-terminal domain at levels of calcium associated cellular activation. In comparison, occupancy of calcium-binding sites in the N-domain of CaM mirrors the calcium-dependence of RyR1 inhibition observed at activating calcium levels, where [Ca]1/2 = 4.3 0.4 μM, suggesting a direct regulation of Ry

  18. Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sebastian Gehlert

    Full Text Available BACKGROUND: While ryanodine receptor 1 (RyR1 critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³ results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. PURPOSE: Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers. METHODS: 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques. RESULTS: While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01 post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05. pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01 in type I and II myofibers and in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and

  19. Ryanodine receptor mutations presenting as idiopathic ventricular fibrillation: a report on two novel familial compound mutations, c.6224T>C and c.13781A>G, with the clinical presentation of idiopathic ventricular fibrillation.

    Science.gov (United States)

    Paech, Christian; Gebauer, Roman Antonin; Karstedt, Jens; Marschall, Christoph; Bollmann, Andreas; Husser, Daniela

    2014-12-01

    Idiopathic ventricular fibrillation (IVF) is a rare genetically determined disease causing unexpected cardiac death in otherwise healthy individuals. This study identified two novel, functional heterozygous mutations in the ryanodine receptor 2 (RyR2) gene in a family with IVF. In the presented case all the patients received a thorough diagnostic workup to exclude structural heart disease. Blood was drawn from the patients, and genetic testing was performed including amplification and sequencing of splice locations in two exons of the RyR2 gene. The mutations were detected in five symptomatic family members. The genetic status of the five affected family members remains unclear. No clinically affected patient is without mutation. At this writing, one family member with confirmed mutation is asymptomatic. The differentiation between catecholaminergic polymorphic ventricular tachycardia (CPVT) and IVF remains a difficult issue, mainly based on clinical characteristics and gross genetic classification. In our case, the family history, exercise testing, and epinephrine stress testing do not suggest an association of arrhythmia and adrenergic triggers, which makes CPVT rather unlikely despite the fact that genetic testing showed RyR2 mutations. Currently, knowledge concerning the functional meaning of genetic mutations is growing. Future exploration of these functional aspects might give further impetus to allocation of these patients to a specific diagnosis. PMID:24950728

  20. ARRHYTHMOGENIC CALMODULIN MUTATIONS AFFECT THE ACTIVATION AND TERMINATION OF CARDIAC RYANODINE RECEPTOR MEDIATED CA2+ RELEASE

    DEFF Research Database (Denmark)

    Søndergaard, Mads Toft; Chazin, Walter J.; Chen, Wayne S.R.;

    . Taken together, all CaM mutations induced an excessive fractional Ca2+ release from internal Ca2+ stores. Interestingly, we demonstrate that the presence of the RyR2 CaMBD decrease the WT CaM C-lobe apparent KD for Ca2+ binding >80 fold to 30 nM. This suggests that Ca2+ binding to the C-lobe of Ca......M would be nearly saturated at diastolic Ca2+ concentrations (~100 nM), and that the C-lobe of CaM would constitutively anchor to RyR2 in a Ca2+ bound state throughout the ECC cycle. Conversely, the N-lobe of CaM seems poised to be sensing changes in physiological Ca2+ with an apparent KD of ~800 nM in...... the presence of RyR2 CaMBD. The D95V, N97S and D129G mutations lowered the affinity of Ca2+ binding of the C-lobe of CaM, to apparent KDs of ~ 140, 150, and 4000 nM, respectively, consistent with the critical role of these residues in Ca2+ binding to the C-lobe. Thus, we suggest that these mutations...

  1. Mass spectrometric analysis and mutagenesis predict involvement of multiple cysteines in redox regulation of the skeletal muscle ryanodine receptor ion channel complex

    Directory of Open Access Journals (Sweden)

    Evgeniy V Petrotchenko

    2011-01-01

    Full Text Available Evgeniy V Petrotchenko1,2,4, Naohiro Yamaguchi1,3,4, Daniel A Pasek1, Christoph H Borchers1,2, Gerhard Meissner11Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA; 2University of Victoria, Genome BC Proteomics Centre, Victoria, British Columbia, Canada; 3Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA 4Contributed equally to the workAbstract: The tetrameric skeletal muscle ryanodine receptor ion channel complex (RyR1 contains a large number of free cysteines that are potential targets for redox-active molecules. Here, we report the mass spectrometric analysis of free thiols in RyR1 using the lipophilic, thiol-specific probe monobromobimane (MBB. In the presence of reduced glutathione, MBB labeled 14 cysteines per RyR1 subunit in tryptic peptides in five of five experiments. Forty-six additional MBB-labeled cysteines per RyR1 subunit were detected with lower frequency in tryptic peptides, bringing the total number of MBB-labeled cysteines to 60 per RyR1 subunit. A combination of fluorescence detection and mass spectrometry of RyR1, labeled in the presence of reduced and oxidized glutathione, identified two redox-sensitive cysteines (C1040 and C1303. Regulation of RyR activity by reduced and oxidized glutathione was investigated in skeletal muscle mutant RyR1s in which 18 cysteines were substituted with serine or alanine, using a [3H]ryanodine ligand binding assay. Three single-site RyR1 mutants (C1781S, C2436S, and C2606S and two multisite mutants with five and seven substituted cysteines exhibited a reduced redox response compared with wild-type RyR1. The results suggest that multiple cysteines determine the redox state and activity of RyR1.Keywords: mass spectrometry, mutagenesis, ryanodine receptor, redox modification of cysteines

  2. 阿诺碱受体及其亚型2调控因子研究进展%Evolution in Research of Ryanodine Receptors and Its Subtype 2 Regulators

    Institute of Scientific and Technical Information of China (English)

    李玉明; 姬广聚

    2011-01-01

    阿诺碱受体(RyR)是心肌细胞等可兴奋细胞中重要的Ca(2+)释放受体,在维持细胞的兴奋性和生理功能方面起重要作用.研究发现,RyR存在3个亚型,每个亚型都是由4个单体组成的四聚体,后者构成Ca(2+)释放通道.RyR的结构中有调控因子的结合位点,一些内源性调控因子可影响RyR的构型和Ca(2+)释放.结合作者的研究,就RyR的结构功能、RyR2的一些重要内源性调控因子及其调控机制做一简要综述.%Ryanodine receptors (RyR), as intracellular Ca2+ release channels, mediate Ca2+ release from intracellular stores in the sarcoplasmic reticulum and play essential roles in some excitable cells such as cardiac and skeletal cells. Cyclic adenosine diphosphate ribose (cADPR) and FK 506 binding proteins(FKBP) are tightly associated with RyR in these cells. A summary on latest research progress in RyR and some channel modulators for RyR2 was given based on authors' research.

  3. Cardiac Muscarinic Receptor Overexpression in Sudden Infant Death Syndrome

    OpenAIRE

    Livolsi, Angelo; Niederhoffer, Nathalie; Dali-Youcef, Nassim; Rambaud, Caroline; Olexa, Catherine; Mokni, Walid; Gies, Jean-Pierre; Bousquet, Pascal

    2010-01-01

    Background Sudden infant death syndrome (SIDS) remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims. The cardiac level of expression of muscarinic receptors, as well as acety...

  4. PET imaging of human cardiac opioid receptors

    International Nuclear Information System (INIS)

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image μ and δ opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65±8 years old) underwent PET scanning of the chest with [11C]carfentanil ([11C]CFN) and [11C]-N-methyl-naltrindole ([11C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [11C]CFN or [11C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [11C]CFN and [11C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37±0.91 with [11C]CFN and 3.86±0.60 with [11C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [11C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [11C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  5. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  6. Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle

    OpenAIRE

    1993-01-01

    The effects of ruthenium red and the related compounds tetraamine palladium (4APd) and tetraamine platinum (4APt) were studied on the ryanodine activated Ca2+ release channel reconstituted in planar bilayers with the immunoaffinity purified ryanodine receptor. Ruthenium red, applied at submicromolar concentrations to the myoplasmic side (cis), induced an all-or-none flickery block of the ryanodine activated channel. The blocking effect was strongly voltage dependent, as large positive potenti...

  7. AT2 Receptors Targeting Cardiac Protection Post-Myocardial Infarction

    DEFF Research Database (Denmark)

    Kaschina, Elena; Lauer, Dilyara; Schmerler, Patrick; Unger, Thomas; Steckelings, Ulrike Muscha

    2014-01-01

    The angiotensin AT2-receptor mediates tissue protective actions. Its regenerative potential has been tested in multiple disease models including models of myocardial infarction. These studies used different experimental approaches in order to detect AT2-receptor-related effects such as AT2-receptor...... deficiency or overexpression, treatment with an AT1-receptor blocker leading to indirect stimulation of the unopposed AT2-receptor, or studies using AT2-receptor agonists. It is a common finding in these studies that the AT2-receptor improves cardiac function in the early phase post-MI, and that this effect...... is preserved over periods of up to four months. Depending on the experimental protocol, the AT2R also attenuates post-MI left ventricular remodeling or protects the heart from early left ventricular thinning and rupture. In combination with AT1-receptor blockade or deficiency, post-MI cardiac...

  8. 17beta-estradiol rapidly mobilizes intracellular calcium from ryanodine-receptor-gated stores via a PKC-PKA-Erk-dependent pathway in the human eccrine sweat gland cell line NCL-SG3.

    LENUS (Irish Health Repository)

    Muchekehu, Ruth W

    2008-09-01

    We describe a novel rapid non-genomic effect of 17beta-estradiol (E2) on intracellular Ca2+ ([Ca2+]i) signalling in the eccrine sweat gland epithelial cell line NCL-SG3. E2 had no observable effect on basal [Ca2+]i, however exposure of cells to E2 in the presence of the microsomal Ca2+ ATPase pump inhibitor, thapsigargin, produced a secondary, sustained increase in [Ca2+]i compared to thapsigargin treatment alone, where cells responded with a transient single spike-like increase in [Ca2+]i. The E2-induced increase in [Ca2+]i was not dependent on the presence of extracellular calcium and was completely abolished by ryanodine (100 microM). The estrogen receptor antagonist ICI 182,780 (1 microM) prevented the E2-induced effects suggesting a role for the estrogen receptor in the release of [Ca2+]i from ryanodine-receptor-gated stores. The E2-induced effect on [Ca2+]i could also be prevented by the protein kinase C delta (PKCdelta)-specific inhibitor rottlerin (10 microM), the protein kinase A (PKA) inhibitor Rp-adenosine 3\\

  9. Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene

    NARCIS (Netherlands)

    E. Nof; B. Belhassen; M. Arad; Z.A. Bhuiyan; C. Antzelevitch; R. Rosso; R. Fogelman; D. Luria; D. El-Ani; M.M.A.M. Mannens; S. Viskin; M. Eldar; A.A.M. Wilde; M. Glikson

    2011-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phen

  10. Effect of Zn2+ ions on ryanodine binding to sarcoplasmic reticulum of striated muscles in the presence of pyrithione

    Institute of Scientific and Technical Information of China (English)

    Hong XIE; Ke-ying CHEN; Pei-hong ZHU

    2004-01-01

    AIM: To explore whether the differential effects of Zn2+ on ryanodine binding to the sarcoplasmic reticulum (SR)of skeletal and cardiac muscles resulted from different permeability of the SR to Zn2+. METHODS: [3H]ryanodine binding assays were performed to examine the effect of Zn2+ on ryanodine binding to the SR in the presence of pyrithione sodium (PyNa), a specific Zn2+ ionophore. RESULTS: As a control, PyNa up to 50 μmol/L did not induce any effect on ryanodine binding to the SR of cardiac muscle. But PyNa 1-100 μmol/L increased ryanodine binding in skeletal muscle with maximum binding (222.2 %+20.9 % of the control) and inhibited ryanodine binding to 50 % of the control at about 500 μrnol/L. In the presence of PyNa 10 and 50 μmol/L the dose-dependence of the effect of Zn2+ in cardiac muscle was still monophasic and not changed by PyNa, while the biphasic effect of Zn2+in skeletal muscle became monophasic. CONCLUSION: Different permeability of the SR to Zn2+ may account for the differential effects of Zn2+on ryanodine binding in skeletal and cardiac muscles. PyNa is not a strictly specific Zn2+ ionophore.

  11. 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

  12. 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

  13. Expression and reconstitution of the bioluminescent Ca(2+) reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes.

    Science.gov (United States)

    Chan, Harvey Y S; Cheung, Man Chun; Gao, Yi; Miller, Andrew L; Webb, Sarah E

    2016-08-01

    In order to develop a novel method of visualizing possible Ca(2+) signaling during the early differentiation of hESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca(2+) reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca(2+) signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca(2+) transients (generated by release from intracellular stores) were detected in 1-12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or CaCl2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor (IP3R) agonist, small Ca(2+) transients were generated from day 1 onward. That ATP was inducing Ca(2+) release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor (RyR) agonist, a minimal Ca(2+) response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation. PMID:27430888

  14. Positive allosteric action of eburnamonine on cardiac muscarinic acetylcholine receptors.

    Science.gov (United States)

    Proska, J; Tucek, S

    1996-06-01

    It was discovered recently that alcuronium and strychnine (which is a precursor of alcuronium) allosterically increase the affinity of cardiac muscarinic receptors for the antagonist, N-methylscopolamine. We have now investigated the effects of l-eburnamonine and vincamine, which are both closely related to strychnine. In experiments on rat heart atria, l-eburnamonine was found to increase the binding of [3H]N-methylscopolamine with Ehlert's cooperativity coefficient alpha = 0.35, which indicates that the strength of its allosteric action is close to that of alcuronium and strychnine (alpha = 0.31 and 0.44, respectively). However, the affinity of l-eburnamonine for the cardiac muscarinic receptors is lower than the affinities of alcuronium and strychnine (KAR = 22.6 microM, 0.15 microM, and 3.4 microM, respectively). In spite of its extremely close similarity to l-eburnamonine, vincamine has a negative allosteric effect on the binding of [3H]N-methylscopolamine (alpha = 4.1; KAR = 22.8 microM). It is likely that a systematic investigation of the allosteric effects of the analogues of strychnine will not only yield new allosteric effectors on muscarinic receptors, but also clarify the structural features responsible for the direction (positive or negative) of their allosteric effect. PMID:8813554

  15. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice

    OpenAIRE

    Yousif Nasser; Al-amran Fadhil G

    2011-01-01

    Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p.)...

  16. APJ acts as a dual receptor in cardiac hypertrophy.

    Science.gov (United States)

    Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E; Purcell, Nicole H; Catalucci, Daniele; Akasaka, Takeshi; Bueno, Orlando F; Vlasuk, George P; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H; Ashley, Euan; Mercola, Mark; Brown, Joan Heller; Ruiz-Lozano, Pilar

    2012-08-16

    Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy. PMID:22810587

  17. Selective estrogen receptor modulators promising for cardiac syndrome X

    Directory of Open Access Journals (Sweden)

    Chen Y

    2010-01-01

    Full Text Available Cardiac syndrome X (CSX is defined as a typical anginal-like chest pain with a transient ischemic electrocardiogram, but without abnormal coronary angiography. It is usually accepted that endothelial dysfunction, inflammation, oxidative stress and estrogen deficiency are the main reasons of CSX. There are some methods to treat CSX including statins, b blocker, angiotensin converting enzyme inhibitors, nitrates, estrogen, and so on. The estrogen replacement therapy (ERT, in particular, has been reported by many researchers to significantly reduce the frequency of chest pain after administration of estrogen, which has been explained as estrogen acting on its receptor to improve the endothelial function. However, it has been suggested that ERT must not be used for coronary heart disease due to its adverse effects. However, some selective estrogen receptor modulators (SERMs can inhibit inflammatory response as well as oxidative stress, and improve the endothelial function, to reduce the occurrence of chest pain. Here, we hypothesize that SERMs may be the beneficial selection for patients with CSX.

  18. 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

  19. Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice

    OpenAIRE

    1985-01-01

    Administration of the monoclonal antibody M7/20, which binds to the murine interleukin-2 (IL) receptor, significantly prolongs cardiac allograft survival in two H-2-incompatible strain combinations of inbred mice. The results support the important role of the IL-2 receptor in the mechanism of graft rejection, and suggest its suitability as a target for immunosuppressive therapy.

  20. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    OpenAIRE

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

  1. Changes in Negative Charge at the Luminal Mouth of the Pore Alter Ion Handling and Gating in the Cardiac Ryanodine-Receptor

    OpenAIRE

    Mead-Savery, Fiona C.; Wang, Ruiwu; Tanna-Topan, Bhavna; Chen, S. R. Wayne; Welch, William; Williams, Alan J.

    2009-01-01

    We have tested the hypothesis that a high density of negative charge at the luminal mouth of the RyR2 pore plays a pivotal role in the high cation conductance and limited selectivity observed in this channel by introducing into each monomer a double point mutation to neutralize acidic residues in this region of the mouse RyR2 channel. The resultant channel, ED4832AA, is capable of functioning as a calcium-release channel in situ. Consistent with our hypothesis, the ED4832AA mutation altered t...

  2. UniProt search blastx result: AK288850 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288850 J090075H22 Q92736|RYR2_HUMAN Ryanodine receptor 2 (Cardiac muscle -type ryanodine recept ... or) (RyR2) (RYR-2) (Cardiac muscle ... ryanodine receptor-calcium release channel) (hRYR- ...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system...... also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system in...

  4. Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-induced Cardiac Hypertrophy.

    Science.gov (United States)

    Grune, Jana; Benz, Verena; Brix, Sarah; Salatzki, Janek; Blumrich, Annelie; Höft, Beata; Klopfleisch, Robert; Foryst-Ludwig, Anna; Kolkhof, Peter; Kintscher, Ulrich

    2016-05-01

    Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg·kg·d), EPL (200 mg·kg·d) or vehicle (VEH). First, we analyzed cardiac gene expression 4 weeks after TAC using a pathway-focused quantitative polymerase chain reaction array. FIN caused a distinct cardiac gene expression profile compared to VEH and EPL, including differential expression of BNP (brain natriuretic peptide) and Tnnt2 (troponin T type 2). FIN treatment led to a significant reduction of TAC-induced left ventricular (LV) wall thickening assessed by echocardiography. In accordance, FIN-treated mice showed a significant lower increase of calculated left ventricular mass compared with VEH- and EPL-treated mice (FIN: 28.4 ± 3.7 mg; EPL: 38.4 ± 4.3 mg; VEH: 39.3 ± 3.1 mg; P < 0.05). These data show beneficial effects of nonsteroidal MR antagonism by FIN on left ventricular mass development in pressure overload associated with a distinct cardiac gene expression profile. PMID:26859196

  5. Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase

    OpenAIRE

    Dong, MQ; Sun, HY; Tang, Q.; Tse, HF; Lau, CP; Li, GR

    2010-01-01

    The aim of the present study was to investigate whether/how the recombinant human cardiac I Ks could be regulated by epidermal growth factor receptor kinase in HEK 293 cells stably expressing hKCNQ1/hKCNE1 genes using the approaches of perforated patch clamp technique, immunoprecipitation and Western blot analysis. It was found that the broad spectrum isoflavone tyrosine kinase inhibitor genistein and the selective epidermal growth factor receptor kinase inhibitor tyrphostin AG556 suppressed ...

  6. Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis

    Directory of Open Access Journals (Sweden)

    Ralph Lohner

    2013-01-01

    Full Text Available Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9 in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP in C57BL/6 wild-type (WT and TLR9-deficient (TLR9-D mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.

  7. APJ ACTS AS A DUAL RECEPTOR IN CARDIAC HYPERTROPHY

    OpenAIRE

    Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Metzler, Scott; Wei, Ke; Wang, Jianming; Woods, Chris E.; Purcell, Nicole H.; Catalucci, Daniele; Akasaka, Takashi; Bueno, Orlando F.; Vlasuk, George P.; Kaliman, Perla; Bodmer, Rolf; Smith, Layton H.

    2012-01-01

    Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues 1 . Here we report that genetic loss of APJ confers resistance to chronic pressure overload by dramatically reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to s...

  8. Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.

    Science.gov (United States)

    Xavier-Neto, José; Sousa Costa, Ângela M; Figueira, Ana Carolina M; Caiaffa, Carlo Donato; Amaral, Fabio Neves do; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R; Castillo, Hozana Andrade

    2015-02-01

    Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development. PMID:25134739

  9. 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

  10. Cardiac mast cells regulate myocyte ANP release via histamine H2 receptor in beating rabbit atria.

    Science.gov (United States)

    Li, Dan; Wen, Jin Fu; Jin, Jing Yu; Quan, He Xiu; Cho, Kyung Woo

    2009-06-01

    It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H(2) receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell-cardiomyocyte communication via the histamine-ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy. PMID:19328828

  11. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Aparici, C.M.; Martin, J.C.; Tembl, A.; Flotats, A.; Estorch, M.; Catafau, A.M.; Berna, L.; Carrio, I. [Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Narula, J.; Puig, M.; Camprecios, M.; Ballester, M. [Cardiology Department, Sant Pau Hospital, Barcelona (Spain)

    2000-12-01

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. {sup 111}In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  12. Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy

    International Nuclear Information System (INIS)

    The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the

  13. SIGNALLING THROUGH RETINOIC ACID RECEPTORS IN CARDIAC DEVELOPMENT: DOING THE RIGHT THINGS AT THE RIGHT TIMES

    Science.gov (United States)

    Xavier-Neto, José; Costa, Ângela M. Sousa; Figueira, Ana Carolina M.; Caiaffa, Carlo Donato; do Amaral, Fabio Neves; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R.; Castillo, Hozana Andrade

    2015-01-01

    Retinoic acid (RA) is a terpenoid that is synthesized from Vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinic and experimental data provide uncontested evidence for the pleiotropic roles of RA signalling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signalling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signalling is exquisitely regulated according to specific phases of cardiac development and that RA signalling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signalling by RA receptors (RARs) in early phases of heart development. PMID:25134739

  14. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.

    Science.gov (United States)

    Yang, Shaolong; Hu, Shunhua; Choudhry, Mashkoor A; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2007-03-01

    Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely

  15. The effects of Vigna unguiculata on cardiac oxidative stress and aorta estrogen receptor-β expression of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Etik Khusniyati

    2014-12-01

    Conclusions: V. unguiculata is an alternative therapy in decreasing cardiac oxidative stress in ovariectomized rats. Besides, high dose of V. unguiculata also able to increase aorta estrogen receptor-β expression in ovariectomized rats.

  16. Glucocorticoid-Induced Hypertension and Cardiac Injury: Effects of Mineralocorticoid and Glucocorticoid Receptor Antagonism

    Directory of Open Access Journals (Sweden)

    KOHZO NAGATA

    2013-02-01

    Full Text Available Glucocorticoids are widely administered for the treatment of various disorders, although their long-term use results in adverse effects associated with glucocorticoid excess. We investigated the pathophysiological roles of glucocorticoid receptors (GRs and mineralocorticoid receptors (MRs in the cardiac changes induced by exogenous corticosterone in rats. Corticosterone or vehicle was injected twice daily in rats from 8 to 12 weeks of age. The effects of the GR antagonist RU 486, the MR antagonist spironolactone, or both agents on corticosterone action were also determined. Corticosterone induced hypertension, left ventricular (LV fibrosis, and LV diastolic dysfunction. Neither RU 486 nor spironolactone affected corticosteroneinduced hypertension, whereas spironolactone, but not RU 486, attenuated the effects of corticosterone on LV fibrosis and diastolic function. Corticosterone also increased cardiac oxidative stress and inflammation in a manner sensitive to spironolactone but not to RU 486. The corticosterone-induced LV atrophy was not affected by either RU 486 or spironolactone. Our results implicate MRs in the cardiac fibrosis and diastolic dysfunction, but not MRs or GRs in the cardiac atrophy, induced by corticosterone. Neither MRs nor GRs appear to contribute to corticosterone-induced hypertension.

  17. Cardiac gene expression data and in silico analysis provide novel insights into human and mouse taste receptor gene regulation.

    Science.gov (United States)

    Foster, Simon R; Porrello, Enzo R; Stefani, Maurizio; Smith, Nicola J; Molenaar, Peter; dos Remedios, Cristobal G; Thomas, Walter G; Ramialison, Mirana

    2015-10-01

    G protein-coupled receptors are the principal mediators of the sweet, umami, bitter, and fat taste qualities in mammals. Intriguingly, the taste receptors are also expressed outside of the oral cavity, including in the gut, airways, brain, and heart, where they have additional functions and contribute to disease. However, there is little known about the mechanisms governing the transcriptional regulation of taste receptor genes. Following our recent delineation of taste receptors in the heart, we investigated the genomic loci encoding for taste receptors to gain insight into the regulatory mechanisms that drive their expression in the heart. Gene expression analyses of healthy and diseased human and mouse hearts showed coordinated expression for a subset of chromosomally clustered taste receptors. This chromosomal clustering mirrored the cardiac expression profile, suggesting that a common gene regulatory block may control the taste receptor locus. We identified unique domains with strong regulatory potential in the vicinity of taste receptor genes. We also performed de novo motif enrichment in the proximal promoter regions and found several overrepresented DNA motifs in cardiac taste receptor gene promoters corresponding to ubiquitous and cardiac-specific transcription factor binding sites. Thus, combining cardiac gene expression data with bioinformatic analyses, this study has provided insights into the noncoding regulatory landscape for taste GPCRs. These findings also have broader relevance for the study of taste GPCRs outside of the classical gustatory system, where understanding the mechanisms controlling the expression of these receptors may have implications for future therapeutic development. PMID:25986534

  18. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin induced cardiac injury in mice

    Directory of Open Access Journals (Sweden)

    Yousif Nasser

    2011-10-01

    Full Text Available Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin induced cardiac toxicity. Toll-like receptors (TLRs are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p., left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+ and HeJ mutant (TLR4-/- treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α, Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN, in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p -/-; p -/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1, so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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. Angiotensin II type 1 receptor signalling regulates microRNA differentially in cardiac fibroblasts and myocytes

    DEFF Research Database (Denmark)

    Jeppesen, Pia Lindgren; Christensen, Gitte Lund; Schneider, Mikael; Nossent, Anne Yaël; Jensen, Hasse Brønnum; Andersen, Ditte Caroline; Eskildsen, Tilde; Gammeltoft, Steen; Hansen, Jakob Lerche; Sheikh, Søren Paludan

    2011-01-01

    Background and purpose: The Angiotensin II type 1 receptor (AT(1) R) is a key regulator of blood pressure and cardiac contractility and is profoundly involved in development of cardiac disease. Since several microRNAs (miRNAs) have been implicated in cardiac disease, we asked whether miRNAs might...... be regulated by AT(1) R signals in a Gaq/11 dependent or -independent manner. Experimental approach: We performed a global miRNA array analysis of angiotensin II (Ang II) mediated miRNA regulation in HEK293N cells over-expressing the AT(1) R and focused on separating the role of Gaq/11 -dependent and...... -independent pathways. MiRNA regulation was verified with quantitative PCR in both HEK293N cells and primary cardiac myocytes and fibroblasts. Key results: Our studies revealed five miRNAs (miR-29b, -129-3p, -132, -132* and -212) that were upregulated by Ang II in HEK293N cells. In contrast, the biased Ang II...

  2. Expressions of cardiac sympathetic norepinephrine transporter and β1-adrenergic receptor decreased in aged rats

    Institute of Scientific and Technical Information of China (English)

    He LI; Xiao-qing MA; Fan YE; Jing ZHANG; Xin ZHOU; Zhi-hong WANG; Yu-ming LI; Guo-yuan ZHANG

    2009-01-01

    Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovas-cular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine (NE) transporter (NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleff and maintains the sensitivity of the β-adrenergic receptor (β-AR). In the present study, we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and leff ventricular myocardium in 2- and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA, NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%, 26%, and 43%, respectively, in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.

  3. INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN-1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET-1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET-1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET-1 levels increased significantly on week 2 and week 4 of pressure overload. ET-1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41% (P<0.01) and 65% (P< 0.01) in sarcolemma in H-2 week and H-4 week groups, but was decreased by 24% (P< 0.01) and 21% (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33% (P< 0.01) and 57% (P< 0.01) in group H-2 week and H-4 week, respectively. ? Conclusion. ET-1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.

  4. INTRACELLULAR REDISTRIBUTION OF CARDIAC ENDOTHELIN-1 RECEPTOR IN RAT DURING MYOCARDIAL HYPERTROPHYA

    Institute of Scientific and Technical Information of China (English)

    王晓红; 齐永芬; 杨军; 佟利家; 庞永正; 唐朝枢

    2001-01-01

    Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET-1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominalaorta of rats, and ET-1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET-1 levels increased significantly on week 2 and week 4 ofpressure overload. ET-1 binding studies showed that during myocardial hypertrophy, the maximum binding capaci-ty (Bmax) was increased by 41% ( P < 0. 01) and 65% ( P < 0. 01) in sarcolemma in H-2 week and H-4 weekgroups, but was decreased by 24% (P <0.01) and 21% (P <0.01) in light vesicles. The sum of Bmax ofsarcolemmal and light vesicle fractions was increased by 33% ( P < 0. 01 ) and 57% ( P < 0.01 ) in group H-2 week and H-4 week, respectively. Conclusion. ET-1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.

  5. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    International Nuclear Information System (INIS)

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22phox, p47phox, p67phox, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H2O2. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen formation

  6. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

  7. 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

  8. Membrane Localization, Caveolin-3 Association and Rapid Actions of Vitamin D Receptor in Cardiac Myocytes

    OpenAIRE

    Zhao, Guisheng; Simpson, Robert U.

    2009-01-01

    The active form of vitamin D, 1alpha, 25-Dihydroxyvitamin D3 (1, 25(OH)2D3), mediates both genomic and rapid non-genomic actions in heart cells. We have previously shown that the vitamin D receptor (VDR) is located in the t-tubular structure of cardiomyocytes. Here we show that VDR specifically interacts with Caveolin-3 in the t-tubules and sarcolemma of adult rat cardiac myocytes. Co-Immunoprecipitation studies using VDR antibodies revealed that Caveolin-3 specifically co-precipitates with t...

  9. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

    OpenAIRE

    Fu, Liang-Wu; Longhurst, John C.

    2013-01-01

    Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischem...

  10. The Cardiac Ventricular 5-HT4 Receptor Is Functional in Late Foetal Development and Is Reactivated in Heart Failure

    OpenAIRE

    Brattelid, Trond; Qvigstad, Eirik; Moltzau, Lise R; Bekkevold, Silje V. S.; Sandnes, Dagny L; Birkeland, Jon Arne K.; Skomedal, Tor; Osnes, Jan-Bjørn; Sjaastad, Ivar; Levy, Finn Olav

    2012-01-01

    A positive inotropic responsiveness to serotonin, mediated by 5-HT4 and 5-HT2A receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expe...

  11. Ah Receptor Signaling Controls the Expression of Cardiac Development and Homeostasis Genes.

    Science.gov (United States)

    Carreira, Vinicius S; Fan, Yunxia; Wang, Qing; Zhang, Xiang; Kurita, Hisaka; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-10-01

    Congenital heart disease (CHD) is the most common congenital abnormality and one of the leading causes of newborn death throughout the world. Despite much emerging scientific information, the precise etiology of this disease remains elusive. Here, we show that the aryl hydrocarbon receptor (AHR) regulates the expression of crucial cardiogenesis genes and that interference with endogenous AHR functions, either by gene ablation or by agonist exposure during early development, causes overlapping structural and functional cardiac abnormalities that lead to altered fetal heart physiology, including higher heart rates, right and left ventricle dilation, higher stroke volume, and reduced ejection fraction. With striking similarity between AHR knockout (Ahr(-/-)) and agonist-exposed wild type (Ahr(+/+)) embryos, in utero disruption of endogenous AHR functions converge into dysregulation of molecular mechanisms needed for attainment and maintenance of cardiac differentiation, including the pivotal signals regulated by the cardiogenic transcription factor NKH2.5, energy balance via oxidative phosphorylation and TCA cycle and global mitochondrial function and homeostasis. Our findings suggest that AHR signaling in the developing mammalian heart is central to the regulation of pathways crucial for cellular metabolism, cardiogenesis, and cardiac function, which are potential targets of environmental factors associated with CHD. PMID:26139165

  12. (Prorenin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function.

    Directory of Open Access Journals (Sweden)

    Anne-Mari Moilanen

    Full Text Available BACKGROUND: Activation of the renin-angiotensin-system (RAS plays a key pathophysiological role in heart failure in patients with hypertension and myocardial infarction. However, the function of (prorenin receptor ((PRR is not yet solved. We determined here the direct functional and structural effects of (PRR in the heart. METHODOLOGY/PRINCIPAL FINDINGS: (PRR was overexpressed by using adenovirus-mediated gene delivery in normal adult rat hearts up to 2 weeks. (PRR gene delivery into the anterior wall of the left ventricle decreased ejection fraction (P<0.01, fractional shortening (P<0.01, and intraventricular septum diastolic and systolic thickness, associated with approximately 2-fold increase in left ventricular (PRR protein levels at 2 weeks. To test whether the worsening of cardiac function and structure by (PRR gene overexpression was mediated by angiotensin II (Ang II, we infused an AT(1 receptor blocker losartan via osmotic minipumps. Remarkably, cardiac function deteriorated in losartan-treated (PRR overexpressing animals as well. Intramyocardial (PRR gene delivery also resulted in Ang II-independent activation of extracellular-signal-regulated kinase1/2 phosphorylation and myocardial fibrosis, and the expression of transforming growth factor-β1 and connective tissue growth factor genes. In contrast, activation of heat shock protein 27 phosphorylation and apoptotic cell death by (PRR gene delivery was Ang II-dependent. Finally, (PRR overexpression significantly increased direct protein-protein interaction between (PRR and promyelocytic zinc-finger protein. CONCLUSIONS/SIGNIFICANCE: These results indicate for the first time that (PRR triggers distinct Ang II-independent myocardial fibrosis and deterioration of cardiac function in normal adult heart and identify (PRR as a novel therapeutic target to optimize RAS blockade in failing hearts.

  13. EXTERNALIZATION AND INTERNALIZATION OF CARDIAC ENDOTHELIN RECEPTORS DURING DIFFERENT PHASES OF SEPSIS IN RAT

    Institute of Scientific and Technical Information of China (English)

    王晓红; 杨军; 董林旺; 庞永政; 苏静怡; 唐朝枢; 刘乃奎

    2001-01-01

    Objective. To study the redistribution of endothelin-1 (ET-1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]-ET1 binding. Marker enzyme activities, protein yield, and dry-to-wet weight ratio of cardiac membranes were measured. Results. Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]-ET1 binding study showed that during early stage of sepsis, the Bmax of ET1 receptors was increased by 30% in sarcolemma but decreased by 19% in light vesicles, while during late stage of sepsis, the Bmax was decreased by 24% in sarcolemma but increased by 38% in light vesicles.The total binding of sarcolemma and light vesicles was increased by 25% during early stage of sepsis but decreased by 17% during late stage of sepsis. Conclusions. These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.

  14. Angiotensin II (AT1) Receptor Blockade Reduces Vascular Tissue Factor in Angiotensin II-Induced Cardiac Vasculopathy

    OpenAIRE

    Dominik N Müller; Mervaala, Eero M A; Dechend, Ralf; Fiebeler, Anette; Park, Joon-Keun; Schmidt, Folke; Theuer, Jürgen; Breu, Volker; Mackman, Nigel; Luther, Thomas; Schneider, Wolfgang; Gulba, Dietrich; Ganten, Detlev; Haller, Hermann; Luft, Friedrich C.

    2000-01-01

    Tissue factor (TF), a main initiator of clotting, is up-regulated in vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II receptor AT1 receptor blockade inhibits TF expression in a model of ANG II-induced cardiac vasculopathy. Furthermore, we explored the mechanisms by examining transcription factor activation and analyzing the TF promoter. Untreated transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) feature hypertension and severe left...

  15. Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

    Science.gov (United States)

    Wagner, Kay-Dietrich; Vukolic, Ana; Baudouy, Delphine; Michiels, Jean-François

    2016-01-01

    Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease. PMID:27057154

  16. Association between Angiotensin II Type 1 Receptor Polymorphism and Sudden Cardiac Death in Myocardial Infarction

    Science.gov (United States)

    Kruzliak, Peter; Kovacova, Gabriela; Pechanova, Olga; Balogh, Stefan

    2013-01-01

    Objective. The renin-angiotensin system is involved in the pathogenesis of coronary artery disease and myocardial infarction (MI). Angiotensin II (Ang II) has many adverse effects such as vasoconstriction and vascular remodeling, and these actions are mediated by the angiotensin II type 1 receptor (AT1R). Patients and Methods. A total of 1376 patients were recruited from January 2010 to April 2012. The study group consisted of 749 patients with ACS (317 females and 432 males) and of 627 healthy controls. Results. The ACS patients demonstrated a lower proportion of AA genotypes and AC genotypes but higher proportions of CC genotypes than the control population. The AT1R CC genotype conferred a 2.76-fold higher risk of MI compared with the genotype AC and AA. In addition, the CC genotype was also associated with a 4.08 times higher risk of left anterior descending artery infarction and a 3.07 times higher risk of anterior wall infarction. We also found that the CC genotype was independently associated with sudden cardiac death. In Summary. This study demonstrated that the AT1R CC genotype is an independent risk factor for ACS incidence, and this genotype is associated with a greater ACS severity and greater risk of sudden cardiac death. PMID:24167376

  17. Protection by 6-aminonicotinamide against oxidative stress in cardiac cells

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Sigurdardottir, Kristin Sigridur; Treiman, Marek

    2006-01-01

    Oxidative stress at the time of reperfusion is a major aspect of ischemia-reperfusion injury in heart as well as in other organs. There is a continuing interest in development of pharmacological approaches to alleviate this injury. 6-Aminonicotinamide (6AN) has been shown to diminish myocardial...... necrosis following global ischemia in an isolated rat heart, apparently by limiting the oxidative injury component. We therefore explored the antioxidative potential of 6AN in a model using H9C2(2-1) rat cardiac myoblasts exposed to H2O2 stress. Dependent on the specific protocol, 6AN pretreatment for 6...... protective effect of 6AN was associated with a decrease in total cell content of the reduced glutathione (GSH) by 15-44%, indicative of an oxidative shift in the GSH/GSSG system redox potential. We propose that this redox shift caused an increased Ca2+ leak through ryanodine receptors, reflecting their known...

  18. Differences in affinity of cardiac beta-adrenergic receptors for [3H]dihydroalprenolol

    International Nuclear Information System (INIS)

    We performed quantitative light microscopic autoradiography of [3H]dihydroalprenolol (DHA) binding to frozen sections of canine myocardium to test the hypothesis that there are differences in the density or affinity of beta-adrenergic receptors on various tissue compartments. In one study, with concentrations of [3H]DHA from 0.34 to 5.1 nM, specific binding to cardiac myocytes was saturable, whereas nonspecific binding was linear with ligand concentration. Arterioles had more specific grain counts than muscle cells (P less than 0.0001), and Scatchard analysis showed that the arterioles had a much higher affinity for [3H]DHA than myocytes. In a second study with lower concentrations of [3H]DHA (0.19-1.98 nM), binding to the arterioles saturated, whereas binding to the cardiac myocytes did not. Specific binding to arterioles was significantly higher (P less than 0.0001) than binding to myocytes at all concentrations of [3H]DHA. The dissociation constants for the subendocardial and subepicardial myocytes were 1.57 and 1.71 nM, respectively, while the dissociation constant for the arterioles was 0.26 nM. The maximum number of binding sites was 911 grains/0.9 X 10(-2) mm2 for subepicardial myocytes, 936 for subendocardial myocytes, and 986 for arterioles. The large nerves accompanying an epicardial artery also demonstrated specific [3H]DHA binding. Thus this study has demonstrated major differences in the distribution and affinity of beta-adrenergic receptors, which may help to explain various physiological responses to beta-adrenergic stimulation

  19. Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

    Science.gov (United States)

    Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

    1984-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

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

    Science.gov (United States)

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

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

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

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

  2. Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation.

    Science.gov (United States)

    Drowley, Lauren; Koonce, Chad; Peel, Samantha; Jonebring, Anna; Plowright, Alleyn T; Kattman, Steven J; Andersson, Henrik; Anson, Blake; Swanson, Bradley J; Wang, Qing-Dong; Brolen, Gabriella

    2016-02-01

    Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-β type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic

  3. Effects of Peroxisome Proliferator-Activated Receptor-δ Agonist on Cardiac Healing after Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Jeong Rang Park

    Full Text Available Peroxisome proliferator-activated receptor-delta (PPAR-δ-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect.

  4. Suppression of calcium‑sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy.

    Science.gov (United States)

    Liu, Lei; Wang, Chao; Lin, Yan; Xi, Yuhui; Li, Hong; Shi, Sa; Li, Hongzhu; Zhang, Weihua; Zhao, Yajun; Tian, Ye; Xu, Changqing; Wang, Lina

    2016-07-01

    The calcium-sensing receptor (CaSR) releases intracellular calcium ([Ca2+]i) by accumulating inositol phosphate. Changes in [Ca2+]i initiate myocardial hypertrophy. Furthermore, autophagy associated with [Ca2+]i. Autophagy has previously been demonstrated to participate in the hypertrophic process. The current study investigated whether suppression of CaSR affects the hypertrophic response via modulating autophagy. Isoproterenol (ISO) was used to induce cardiac hypertrophy in Wistar rats. Hypertrophic status was determined by echocardiographic assessment, hematoxylin and eosin, and Masson's staining. The protein expression levels of CaSR and autophagy level were observed. Changes of hypertrophy and autophagy indicators were observed following intravenous injection of a CaSR inhibitor. An ISO‑induced cardiomyocyte hypertrophy model was established and used determine the involvement of GdCl3. [Ca2+]i was determined using Fluo‑4/AM dye followed by confocal microscopy. The expression levels of various active proteins were analyzed by western blotting. The size of the heart, expression levels of CaSR and autophagy level were markedly increased in hypertrophic myocardium. In addition, the present study demonstrated that the indicators of hypertrophy and autophagy were effectively suppressed by CaSR inhibitor. Furthermore, similar effects were demonstrated in neonatal rat hypertrophic cardiomyocytes treated with ISO. It was also observed that CaSR regulates the Ca2+/calmodulin‑dependent protein kinase kinase β (CaMKKβ)‑AMP‑activated protein kinase (AMPK)‑mammalian target of rapamycin (mTOR) signaling pathway induced by ISO in cardiomyocytes. Furthermore, the AMPK inhibition significantly reduced the autophagy level following CaSR stimulation (P<0.05). The results of the present demonstrated that inhibition of CaSR may ameliorate cardiac hypertrophy induced by ISO and the effect may be associated with the inhibition of autophagy and suppression of the Ca

  5. Prevention by NMDA receptor antagonists of the centrally-evoked increases of cardiac inotropic responses in rabbits.

    OpenAIRE

    Monassier, L.; Tibiriça, E.; Roegel, J. C.; Mettauer, B.; Feldman, J.; Bousquet, P.

    1994-01-01

    1. The purpose of this study was to investigate further the role of the excitatory amino acid (EAA) system of neurotransmission, particularly of the NMDA receptor, in the central regulation of cardiac function. 2. Electrical stimulation of the paraventricular nucleus of the hypothalamus (PVN) in pentobarbitone anaesthetized rabbits induced a cardiovascular response mainly characterized by a positive inotropic effect, hypertension and a marked increase in the myocardial oxygen demand index. 3....

  6. Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4

    Science.gov (United States)

    Maqbool, Azhar; Spary, Emma J; Manfield, Iain W; Ruhmann, Michaela; Zuliani-Alvarez, Lorena; Gamboa-Esteves, Filomena O; Porter, Karen E; Drinkhill, Mark J; Midwood, Kim S; Turner, Neil A

    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 (CMF). METHODS: CMF were isolated and cultured from patients undergoing coronary artery bypass grafting. Cultured cells were treated with either TNC (0.1 μmol/L, 24 h) or a recombinant protein corresponding to different domains of the TNC protein; fibrinogen-like globe (FBG) and fibronectin type III-like repeats (TNIII 5-7) (both 1 μmol/L, 24 h). The expression of the pro-inflammatory cytokines; interleukin (IL)-6, IL-1β, TNFα and the matrix metalloproteinases; MMPs (MMP1, 2, 3, 9, 10, MT1-MMP) was assessed using real time RT-PCR and western blot analysis. RESULTS: TNC increased both IL-6 and MMP3 (P < 0.01) mRNA levels in cultured human CMF but had no significant effect on the other markers studied. The increase in IL-6 mRNA expression was mirrored by an increase in protein secretion as assessed by enzyme-linked immunosorbant assay (P < 0.01). Treating CMF with the recombinant protein FBG increased IL-6 mRNA and protein (P < 0.01) whereas the recombinant protein TNIII 5-7 had no effect. Neither FBG nor TNIII 5-7 had any significant effect on MMP3 expression. The expression of toll-like receptor 4 (TLR4) in human CMF was confirmed by real time RT-PCR, western blot and immunohistochemistry. Pre-incubation of cells with TLR4 neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mRNA and protein expression. CONCLUSION: TNC up-regulates IL-6 expression in human CMF, an effect mediated through the FBG domain of TNC and via the TLR4 receptor. PMID:27231521

  7. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  8. 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

  9. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice

    Science.gov (United States)

    Trentin-Sonoda, Mayra; da Silva, Rogério Cirino; Kmit, Fernanda Vieira; Abrahão, Mariana Vieira; Monnerat Cahli, Gustavo; Brasil, Guilherme Visconde; Muzi-Filho, Humberto; Silva, Paulo André; Tovar-Moll, Fernanda Freire; Vieyra, Adalberto; Medei, Emiliano; Carneiro-Ramos, Marcela Sorelli

    2015-01-01

    We investigated whether the pathways linked to Toll-like receptors 2 and 4 (TLRs) are involved in renal ischemia-reperfusion (I/R)-induced cardiac hypertrophy. Wild type (WT) C57BL/6J, TLR2-/- and TLR4-/- mice were subjected to left kidney ischemia for 60 min followed by reperfusion for 5, 8, 12 and 15 days. Proton density magnetic resonance showed alterations in the injured kidney from WT mice, together with signs of parenchymal edema and higher levels of vimentin mRNA, accompanied by: (i) small, but significant, increase in serum urea after 24 h, (ii) 100% increase in serum creatinine at 24 h. A serum peak of inflammatory cytokines occurred after 5 days of reperfusion. Heart weight/body weight and heart weight/tibia length ratios increased after 12 and 15 days of reperfusion, respectively. Cardiac hypertrophy markers, B-type natriuretic peptide (BNP) and α-actin, left ventricle mass, cardiac wall thickness and myocyte width increased after 15 days of reperfusion, together with longer QTc and action potential duration. Cardiac TLRs, MyD88, HSP60 and HSP70 mRNA levels also increased. After 15 days of reperfusion, absence of TLRs prevented cardiac hypertrophy, as reflected by similar values of left ventricular cardiac mass and heart weight/body weight ratio compared to the transgenic Sham. Renal tissular injury also ameliorated in both knockout mice, as revealed by the comparison of their vimentin mRNA levels with those found in the WT on the same day after I/R. The I/R TLR2-/- group had TNF-α, IFN-γ and IL-1β levels similar to the non-I/R group, whereas the TLR4-/- group conserved the p-NF-κB/NF- κB ratio contrasting with that found in TLR2-/-. We conclude: (i) TLRs are involved in renal I/R-induced cardiac hypertrophy; (ii) absence of TLRs prevents I/R-induced cardiac hypertrophy, despite renal lesions seeming to evolve towards those of chronic disease; (iii) TLR2 and TLR4 selectively regulate the systemic inflammatory profile and NF- κB activation. PMID

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

    International Nuclear Information System (INIS)

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

  11. Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy

    Science.gov (United States)

    Cai, Yin; Tang, Eva Hoi Ching; Ma, Haichun

    2016-01-01

    Prostaglandin E2 (PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2 are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac-specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects. PMID:27190998

  12. TWEAK-Fn14 cytokine-receptor axis: a new player of myocardial remodeling and cardiac failure

    Directory of Open Access Journals (Sweden)

    Tatyana eNovoyatleva

    2014-02-01

    Full Text Available Tumor necrosis factor (TNF has been firmly established as a pathogenic factor in heart failure, a significant socio-economic burden. In this review we will explore the role of other members of the TNF/TNF receptor superfamily (TNFSF/TNFRSF in cardiovascular diseases (CVDs focusing on TWEAK and its receptor Fn14, new players in myocardial remodeling and heart failure. The TWEAK/Fn14 pathway controls a variety of cellular activities such as proliferation, differentiation and apoptosis and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with CVDs. Furthermore, it has recently been shown that the TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy and that deletion of Fn14 receptor protects from right heart fibrosis and dysfunction. We discuss the potential use of the TWEAK/Fn14 axis as biomarker for CVDs as well as therapeutic target for future treatment of human heart failure based on supporting data from animal models and in vitro studies. Collectively, existing data strongly suggest the TWEAK/Fn14 axis as a potential new therapeutic target for achieving cardiac protection in patients with CVDs.

  13. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    Directory of Open Access Journals (Sweden)

    Daniela L Buscariollo

    Full Text Available Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg or vehicle (0.09% NaCl i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  14. Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism.

    Science.gov (United States)

    Sassoon, Daniel J; Goodwill, Adam G; Noblet, Jillian N; Conteh, Abass M; Herring, B Paul; McClintick, Jeanette N; Tune, Johnathan D; Mather, Kieren J

    2016-07-01

    This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca(2+) binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion. PMID:27234258

  15. 5-HT1A/7 receptor agonist excites cardiac vagal neurons via inhibition of both GABAergic and glycinergic inputs

    Institute of Scientific and Technical Information of China (English)

    Yong-hua CHEN; Li-li HOU; Ji-jiang WANG

    2008-01-01

    Aim: To study the synaptic mechanisms involved in the 5-hydroxytryptaminel AF/7 (5-HT1A/7) receptor-mediated reflex control of cardiac vagal preganglionic neurons (CVPN). Methods: CVPN were retrogradely labeled and identified in brain stem slices of newborn rats, and their synaptic activity was examined using whole-cell patch-clamp. Results: 8-Hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), an agonist of 5-HT1A/7 receptors, had no effect on the glutamatergic inputs of CVPN. In contrast, it significantly decreased the frequency and the amplitude of both the GABAergic and the glycinergic spontaneous inhibitory postsynaptic currents (slPSC). 8-OH-DPAT also caused significant amplitude decrease of the GABAergic currents evoked by stimulation of the nucleus tractus solitarius. Both the fre-quency inhibition and the amplitude inhibition of the GABAergic and the glycinergic sIPSC by 8-OH-DPAT had dose-dependent tendencies and could be reversed by WAY-100635, an antagonist of 5-HT1A/7 receptors. In the pre-exist-ence of tetrodotoxin, 8-OH-DPAT had no effect on the GABAergic or the glycinergic miniature inhibitory postsynaptic currents, and had no effect on the GABAergic or the glycinergic currents evoked by exogenous GABA or glycine. Conclusion:The 5-HT1A/7 receptor agonist excites CVPN indirectly via the inhibition of both the GABAergic and glycinergic inputs. These findings have at least in part re-vealed the synaptic mechanisms involved in the 5-HT1A/7 receptor-mediated reflex control of cardiac vagal nerves in intact animals.

  16. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice

    OpenAIRE

    Trentin-Sonoda, Mayra; da Silva, Rogério Cirino; Kmit, Fernanda Vieira; Abrahão, Mariana Vieira; Monnerat Cahli, Gustavo; Brasil, Guilherme Visconde; Muzi-Filho, Humberto; Silva, Paulo André; Tovar-Moll, Fernanda Freire; Vieyra, Adalberto; Medei, Emiliano; Carneiro-Ramos, Marcela Sorelli

    2015-01-01

    We investigated whether the pathways linked to Toll-like receptors 2 and 4 (TLRs) are involved in renal ischemia-reperfusion (I/R)-induced cardiac hypertrophy. Wild type (WT) C57BL/6J, TLR2-/- and TLR4-/- mice were subjected to left kidney ischemia for 60 min followed by reperfusion for 5, 8, 12 and 15 days. Proton density magnetic resonance showed alterations in the injured kidney from WT mice, together with signs of parenchymal edema and higher levels of vimentin mRNA, accompanied by: (i) s...

  17. Histamine induces postprandian tachycardia through a direct effect on cardiac H2-receptors in pythons

    DEFF Research Database (Denmark)

    Jensen, Nini Skovgaard; Møller, Kate; Gesser, Hans; Wang, Tobias

    2009-01-01

    snakes histamine caused a systemic vasodilatation and a marked increase in heart rate and cardiac output mediated through a direct effect on H2-receptors. Our study strongly indicates that histamine regulates heart rate during the initial phase of digestion in pythons. This study describes a novel...... doubling of intrinsic heart rate. The H2-antagonist did not affect heart rate of fasting snakes, but decreased heart rate by 15-20 min-1 at 24h into digestion, while it had no effects at 48h. Thus, the histaminergic tone on the heart rose from none to 30% at 24h, but vanished after 48h. In anesthetised...

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

    Directory of Open Access Journals (Sweden)

    Maria D. Avila

    2011-01-01

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

  19. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease.

    Science.gov (United States)

    Hernandez, Ciria C; Nascimento, Jose H; Chaves, Elen A; Costa, Patricia C; Masuda, Masako O; Kurtenbach, Eleonora; Campos DE Carvalho, Antonio C; Gimenez, Luis E

    2008-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M(2)-muscarinic acetylcholine receptors (M(2)AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M(2)AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M(2)AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [(3)H]-N-methyl scopolamine ([(3)H]-NMS) in allosterism binding assays. A peptide corresponding to the M(2)AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [(3)H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [(3)H]-NMS dissociation right shifted from an IC(50) of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 x 10(- 8), 1.33 x 10(- 7), and 2.0 x 10(- 7) mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M(2)AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  20. Autoantibodies Enhance Agonist Action and Binding to Cardiac Muscarinic Receptors in Chronic Chagas’ Disease

    Science.gov (United States)

    Hernández, Ciria C.; Nascimento, José H.; Chaves, Elen A.; Costa, Patrícia C.; Masuda, Masako O.; Kurtenbach, Eleonora; Campos de Carvalho, Antônio C.; Giménez, Luis E.

    2009-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M2-muscarinic acetylcholine receptors (M2AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M2AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M2AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [3H]-N-methyl scopolamine ([3H]-NMS) in allosterism binding assays. A peptide corresponding to the M2AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [3H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [3H]-NMS dissociation right shifted from an IC50 of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 × 10−8, 1.33 × 10−7, and 2.0 × 10−7 mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M2AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  1. Cardiac hypertrophy, arrhythmogenicity and the new myocardial phenotype. II. The cellular adaptational process.

    Science.gov (United States)

    Swynghedauw, B; Chevalier, B; Charlemagne, D; Mansier, P; Carré, F

    1997-07-01

    Ventricular fibrosis is not the only structural determinant of arrhythmias in left ventricular hypertrophy. In an experimental model of compensatory cardiac hypertrophy (CCH) the degree of cardiac hypertrophy is also independently linked to ventricular arrhythmias. Cardiac hypertrophy reflects the level of adaptation, and matches the adaptational modifications of the myocardial phenotype. We suggest that these modifications have detrimental aspects. The increased action potential (AP) and QT duration and the prolonged calcium transient both favour spontaneous calcium oscillations, and both are potentially arrhythmogenic and linked to phenotypic changes in membrane proteins. To date, only two ionic currents have been studied in detail: Ito is depressed (likely the main determinant in AP durations), and If, the pacemaker current, is induced in the overloaded ventricular myocytes. In rat CCH, the two components of the sarcoplasmic reticulum, namely Ca(2+)-ATPase and ryanodine receptors, are down-regulated in parallel. Nevertheless, while the inward calcium current is unchanged, the functionally linked duo composed of the Na+/Ca2+ exchanged and (Na+, K+)-ATPase, is less active. Such an imbalance may explain the prolonged calcium transient. The changes in heart rate variability provide information about the state of the autonomic nervous system and has prognostic value even in CCH. Transgenic studies have demonstrated that the myocardial adrenergic and muscarinic receptor content is also a determining factor. During CCH, several phenotypic membrane changes participate in the slowing of contraction velocity and are thus adaptational. They also have a detrimental counterpart and, together with fibrosis, favour arrhythmias. PMID:9302342

  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. Protective effect of prostacyclin against pre-cardiac edema caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin and a thromboxane receptor agonist in developing zebrafish.

    Science.gov (United States)

    Nijoukubo, Daisuke; Tanaka, Yasuaki; Okuno, Yuki; Yin, Guojun; Kitazawa, Takio; Peterson, Richard E; Kubota, Akira; Teraoka, Hiroki

    2016-08-01

    The role of prostaglandin pathways has been suggested in some toxicological responses to dioxins. Cyclooxygenase type 2b (COX2b), thromboxane synthase, and the thromboxane receptor (TP) pathway have been implicated in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced pre-cardiac edema in developing zebrafish at 55 h post fertilization (hpf). Pre-cardiac edema refers to edema located in a small cavity between the heart and body wall of zebrafish eleutheroembryos. In the present study, we assessed the role of prostacyclin, which counteracts some biological effects of thromboxane, in TCDD-induced pre-cardiac edema. Pre-cardiac edema induced by TCDD exposure (0.5 and 1 ppb) beginning at 24 hpf was markedly inhibited by exposure to beraprost (5 and 10 μM), a prostacyclin receptor (IP) agonist, beginning at 33 hpf. The preventive effect of beraprost was reduced by exposure to CAY10441 (10 μM), an IP antagonist starting at 33 hpf. Knockdowns of the IP receptor (IP-KD) with two different morpholinos caused edema by themselves and enhanced pre-cardiac edema caused by the low concentration of TCDD (0.5 ppb). On the other hand, short exposure beginning at 48 hpf to U46619 (7.5-30 μM), a thromboxane receptor agonist caused pre-cardiac edema, which was inhibited by exposure beginning at 48 hpf to both ICI-192,605 (24 μM), a TP antagonist, and beraprost. Expression of prostacyclin synthase was increased from fertilization, plateaued by 48 hpf, and was maintained until at least 96 hpf. Overall, the results demonstrate a preventive effect of prostacyclin on TCDD-induced pre-cardiac edema in developing zebrafish. PMID:27174823

  4. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    International Nuclear Information System (INIS)

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

  5. SIGNALLING THROUGH RETINOIC ACID RECEPTORS IN CARDIAC DEVELOPMENT: DOING THE RIGHT THINGS AT THE RIGHT TIMES

    OpenAIRE

    Xavier-Neto, José; Costa, Ângela M. Sousa; Figueira, Ana Carolina M.; Caiaffa, Carlo Donato; do Amaral, Fabio Neves; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R.; Castillo, Hozana Andrade

    2014-01-01

    Retinoic acid (RA) is a terpenoid that is synthesized from Vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinic and experimental data provide uncontested evidence for the pleiotropic roles of RA signalling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of thes...

  6. Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet.

    Science.gov (United States)

    Han, Jie; Zhang, Song; Ye, Ping; Liu, Yong-Xue; Qin, Yan-Wen; Miao, Dong-Mei

    2016-05-01

    Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT. PMID:26828321

  7. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    Science.gov (United States)

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. PMID:27101299

  8. G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

    DEFF Research Database (Denmark)

    Rokamp, Kim Z; Staalsø, Jonatan M; Gartmann, Martin;

    2013-01-01

    Variation in genes encoding the ß2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q¿ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with ß2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q¿ has not been ...

  9. Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb in rat cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Matsui Hiroki

    2012-12-01

    Full Text Available Abstract Background Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob and the leptin receptor (ob-R in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes. Results Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR. We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII, endothelin-1 (ET-1, or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb gene were significantly increased 4 weeks after banding, but expression of the short form of the leptin receptor (ob-Ra was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress. Conclusions We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.

  10. Inhibition by the tetramine disulphide, benextramine, of cardiac chronotropic histamine H2-receptor-mediated effects.

    OpenAIRE

    Belleau, B.; Benfey, B. G.; Benfey, T. J.; Melchiorre, C.

    1982-01-01

    1 Benextramine (N,N1-bis[o-methoxybenzylamino)-n-hexyl]cystamine), which irreversibly blocks alpha-adrenoceptors and does not inhibit the H1-receptor-mediated contractile effect of histamine on guinea-pig isolated ileum, also did not inhibit the H1-receptor-mediated inotropic effect of histamine on guinea-pig isolated atrium. 2 Benextramine irreversibly inhibited the H2-receptor-mediated chronotropic effect of histamine on guinea-pig isolated atrium. 3 Since its combination with the competiti...

  11. Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac dysfunction in Dahl salt-hypertensive rats in a blood pressure independent manner.

    Directory of Open Access Journals (Sweden)

    Mohammed A Samad

    Full Text Available Proteinuria is a hallmark of chronic kidney disease (CKD and cardiovascular disease (CVD, and a good predictor of clinical outcome. Selective endothelin A (ETA receptor antagonist used with renin-angiotensin system (RAS inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS diet or normal diet (ND for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP, thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition.

  12. Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac dysfunction in Dahl salt-hypertensive rats in a blood pressure independent manner.

    Science.gov (United States)

    Samad, Mohammed A; Kim, Ui Kyoung; Kang, Joshua J; Ke, Qingen; Kang, Peter M

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition. PMID:25775254

  13. Role of adenosine A2A receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control

    International Nuclear Information System (INIS)

    Baroreflex dysfunction contributes to increased cardiovascular risk in cigarette smokers. Given the importance of adenosinergic pathways in baroreflex control, the hypothesis was tested that defective central adenosinergic modulation of cardiac autonomic activity mediates the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1-16 μg/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious rats; slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (25 and 100 μg/kg i.v.) dose-dependently reduced BRSSNP in contrast to no effect on BRSPE. BRSSNP was also attenuated after intracisternal (i.c.) administration of nicotine. Similar reductions in BRSSNP were observed in rats pretreated with atropine or propranolol. The combined treatment with nicotine and atropine produced additive inhibitory effects on BRS, an effect that was not demonstrated upon concurrent exposure to nicotine and propranolol. BRSSNP was reduced in preparations treated with i.c. 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A2A antagonist), or VUF5574 (A3 antagonist). In contrast, BRSSNP was preserved after blockade of A1 (DPCPX) or A2B (alloxazine) receptors or inhibition of adenosine uptake by dipyridamole. CSC or 8-PT abrogated the BRSSNP depressant effect of nicotine whereas other adenosinergic antagonists were without effect. Together, nicotine preferentially impairs reflex tachycardia via disruption of adenosine A2A receptor-mediated facilitation of reflex cardiac sympathoexcitation. Clinically, the attenuation by nicotine of compensatory sympathoexcitation may be detrimental in conditions such as hypothalamic defense response, posture changes, and ventricular rhythms. - Research highlights: → The role of central adenosinergic sites in the nicotine

  14. Recent progress of adrenergic receptors on cardiac hypertrophy%肾上腺素能受体与心肌肥大的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄丹(综述); 毛建文; 李春梅(审校)

    2015-01-01

    心肌肥大是一种较缓慢而有力的代偿形式,然而它不是无限度的,心肌肥大最终将引起心室功能异常而导致心力衰竭,这往往是心血管疾病患者的主要死因之一。肾上腺素能受体(adrenergic receptor,AR)是介导儿茶酚胺作用的一类组织受体,研究表明AR与心肌肥大和心力衰竭的发生密切相关。因此,本文就几种AR与心肌肥大近年的研究进展进行综述,以便更好的了解心肌肥大的发生机理。%Cardiac hypertrophy is a relatively slow but powerful compensatory pattern. However, it is not unlimited, excessive cardiac hypertrophy will eventually cause ventricular dysfunction leading to heart failure, which is one of the main causes of death in patients with cardiovascular disease. Adrenergic receptor is a kind of receptors which mediate the effect of catecholamine. Studies have shown that there is a close relationship between adrenergic receptors and cardiac hypertrophy. Here, we reviewed the advance of study on relationship between adrenergic receptors and cardiac hypertrophy, in recent years. It will help us to better understand the mechanism of cardiac hypertrophy.

  15. Greater adenosine A2A receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C]TMSX PET study

    International Nuclear Information System (INIS)

    We examined the densities of adenosine A2A receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A2A receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A2A receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6±0.3 vs. 3.1±0.4 ml g-1; triceps brachii muscle, 1.7±0.3 vs. 1.2±0.2 ml g-1, respectively). These results indicate that the densities of adenosine A2A receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men

  16. Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II-infused rats.

    Science.gov (United States)

    Minas, Jacqueline N; Thorwald, Max A; Conte, Debra; Vázquez-Medina, Jose-Pablo; Nishiyama, Akira; Ortiz, Rudy M

    2015-11-01

    Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II-dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague-Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II-induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II-mediated increase in plasma and heart aldosterone 2.3- and 1.8-fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1-mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4-hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress-associated cardiovascular damage in Ang II-dependent hypertension. PMID:26234762

  17. Regulation of ryanodine receptor RyR2 by protein-protein interactions: prediction of a PKA binding site on the N-terminal domain of RyR2 and its relation to disease causing mutations [v1; ref status: indexed, http://f1000r.es/4tw

    Directory of Open Access Journals (Sweden)

    Belinda Nazan Walpoth

    2015-01-01

    Full Text Available Protein-protein interactions are the key processes responsible for signaling and function in complex networks. Determining the correct binding partners and predicting the ligand binding sites in the absence of experimental data require predictive models. Hybrid models that combine quantitative atomistic calculations with statistical thermodynamics formulations are valuable tools for bioinformatics predictions. We present a hybrid prediction and analysis model for determining putative binding partners and interpreting the resulting correlations in the yet functionally uncharacterized interactions of the ryanodine RyR2 N-terminal domain. Using extensive docking calculations and libraries of hexameric peptides generated from regulator proteins of the RyR2 channel, we show that the residues 318-323 of protein kinase A, PKA, have a very high affinity for the N-terminal of RyR2. Using a coarse grained Elastic Net Model, we show that the binding site lies at the end of a pathway of evolutionarily conserved residues in RyR2. The two disease causing mutations are also on this path. The program for the prediction of the energetically responsive residues by the Elastic Net Model is freely available on request from the corresponding author.

  18. α1A-Adrenergic receptor prevents cardiac ischemic damage through PKCδ/GLUT1/4-mediated glucose uptake.

    Science.gov (United States)

    Shi, Ting; Papay, Robert S; Perez, Dianne M

    2016-06-01

    While α1-adrenergic receptors (ARs) have been previously shown to limit ischemic cardiac damage, the mechanisms remain unclear. Most previous studies utilized low oxygen conditions in addition to ischemic buffers with glucose deficiencies, but we discovered profound differences if the two conditions are separated. We assessed both mouse neonatal and adult myocytes and HL-1 cells in a series of assays assessing ischemic damage under hypoxic or low glucose conditions. We found that α1-AR stimulation protected against increased lactate dehydrogenase release or Annexin V(+) apoptosis under conditions that were due to low glucose concentration not to hypoxia. The α1-AR antagonist prazosin or nonselective protein kinase C (PKC) inhibitors blocked the protective effect. α1-AR stimulation increased (3)H-deoxyglucose uptake that was blocked with either an inhibitor to glucose transporter 1 or 4 (GLUT1 or GLUT4) or small interfering RNA (siRNA) against PKCδ. GLUT1/4 inhibition also blocked α1-AR-mediated protection from apoptosis. The PKC inhibitor rottlerin or siRNA against PKCδ blocked α1-AR stimulated GLUT1 or GLUT4 plasma membrane translocation. α1-AR stimulation increased plasma membrane concentration of either GLUT1 or GLUT4 in a time-dependent fashion. Transgenic mice overexpressing the α1A-AR but not α1B-AR mice displayed increased glucose uptake and increased GLUT1 and GLUT4 plasma membrane translocation in the adult heart while α1A-AR but not α1B-AR knockout mice displayed lowered glucose uptake and GLUT translocation. Our results suggest that α1-AR activation is anti-apoptotic and protective during cardiac ischemia due to glucose deprivation and not hypoxia by enhancing glucose uptake into the heart via PKCδ-mediated GLUT translocation that may be specific to the α1A-AR subtype. PMID:26832303

  19. Antioxidant/oxidant status and cardiac function in bradykinin B(1)- and B(2)-receptor null mice.

    Science.gov (United States)

    Delemasure, S; Blaes, N; Richard, C; Couture, R; Bader, M; Dutartre, P; Girolami, J-P; Connat, J-L; Rochette, L

    2013-01-01

    Kinin-vasoactive peptides activate two G-protein-coupled receptors (R), B(1)R (inducible) and B(2)R (constitutive). Their complex role in cardiovascular diseases could be related to differential actions on oxidative stress. This study investigated impacts of B(1)R or B(2)R gene deletion in mice on the cardiac function and plasma antioxidant and oxidant status. Echocardiography-Doppler was performed in B(1)R (B(1)R(-/-)) and B(2)R (B(2)R(-/-)) deficient and wild type (WT) adult male mice. No functional alteration was observed in B(2)R(-/-) hearts. B(1)R(-/-) mice had significantly lowered fractional shortening and increased isovolumetric contraction time. The diastolic E and A waves velocity ratio was similar in all mice groups. Thus B(1)R(-/-) mice provide a model of moderate systolic dysfunction, whereas B(2)R(-/-) mice displayed a normal cardiac phenotype. Plasma antioxidant capacity (ORAC) was significantly decreased in both B(1)R(-/-) and B(2)R(-/-) mice whereas the vitamin C levels were decreased in B(2)R(-/-) mice only. Plasma ascorbyl free radical was significantly higher in B(1)R(-/-) compared to WT and B(2)R(-/-) mice. Therefore, the oxidative stress index, ascorbyl free radical to vitamin C ratio, was increased in both B(1)R(-/-) and B(2)R(-/-) mice. Hence, B(1)R and B(2)R deficiency are associated with increased oxidative stress, but there is a differential imbalance between free radical production and antioxidant defense. The interrelationship between the differential B(1)R and B(2)R roles in oxidative stress and cardiovascular diseases remain to be investigated. PMID:24020815

  20. Liganded Peroxisome Proliferator-Activated Receptors (PPARs) Preserve Nuclear Histone Deacetylase 5 Levels in Endothelin-Treated Sprague-Dawley Rat Cardiac Myocytes

    OpenAIRE

    Zhang, Haining; Shao, Zongjun; Alibin, Caroline P.; Acosta, Crystal; Anderson, Hope D

    2014-01-01

    Ligand activation of peroxisome proliferator-activated receptors (PPARs) prevents cardiac myocyte hypertrophy, and we previously reported that diacylglycerol kinase zeta (DGKζ) is critically involved. DGKζ is an intracellular lipid kinase that catalyzes phosphorylation of diacylglycerol; by attenuating DAG signaling, DGKζ suppresses protein kinase C (PKC) and G-protein signaling. Here, we investigated how PPAR-DGKζ signaling blocks activation of the hypertrophic gene program. We focused on ex...

  1. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

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

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains obs...... obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component...

  2. Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with β-receptor blockade.

    Science.gov (United States)

    Watanabe, Heitaro; Iwanaga, Yoshitaka; Miyaji, Yuki; Yamamoto, Hiromi; Miyazaki, Shunichi

    2016-04-01

    Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and β1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of β-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection. PMID:26631854

  3. Coxsackie and adenovirus receptor (CAR) is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia

    Science.gov (United States)

    Marsman, Roos F.J.; Bezzina, Connie R.; Freiberg, Fabian; Verkerk, Arie O.; Adriaens, Michiel E.; Podliesna, Svitlana; Chen, Chen; Purfürst, Bettina; Spallek, Bastian; Koopmann, Tamara T.; Baczko, Istvan; dos Remedios, Cristobal G.; George, Alfred L.; Bishopric, Nanette H.; Lodder, Elisabeth M.; de Bakker, Jacques M.T.; Fischer, Robert; Coronel, Ruben; Wilde, Arthur A.M.; Gotthardt, Michael; Remme, Carol Ann

    2014-01-01

    Objectives To investigate the modulatory effect of the Coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Background A heritable component in risk for ventricular fibrillation (VF) during myocardial infarction (MI) has been well established. A recent genome-wide association study (GWAS) for VF during acute MI has led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the coxsackie and adenovirus receptor (CAR), a cell adhesion molecule predominantly located at intercalated discs of the cardiomyocyte. Methods The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed CAR haploinsufficient mice (CAR+/−). Results In human left ventricular samples, the risk allele at the chr21q21 GWAS locus was associated with lower CXADR mRNA levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced VF. Hearts from CAR+/− mice displayed ventricular conduction slowing in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia following LAD ligation. Connexin43 expression and distribution was unaffected, but CAR+/− hearts displayed increased arrhythmia susceptibility upon pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR+/− myocytes showed reduced sodium current magnitude specifically at the intercalated disc. Moreover, CAR co-precipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. Conclusion We identify CAR as a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk

  4. Effect of chronic metoprolol and coronary occlusion (CO) on cardiac beta receptor density in cats

    International Nuclear Information System (INIS)

    The effect of metoprolol (M) on beta receptor density (BRD) was examined. M (5 mg/kg, p.o., b.i.d.) was given for 2 and 8 wks prior to CO of the left anterior descending artery (LAD) at its origin. BRD, determined by binding of 3H-dihydroalprenol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal LAD distribution, LV = 2 distal LAD distribution, LV3 = posterior left ventricle, RV = right ventricle, and S = septum. A 2 factor ANOVA followed by simple effect and Newman-Keuls post hoc tests revealed that M produced no effect in BRD in LA, RA, LV2, or S. M increased BRD in LV1, LV3, and RV after 2 wk when compared to no M. In addition, BRD in LV3 and RV were also greater at 2 wk than after 8 wk M. The data indicate that there are regional differences in the beta adrenergic receptor densities among the areas of the heart and within the left ventricle. Chronic dosing with M produced increased BRD in only some of the areas of the heart. These differences may be related to functional differences in the various areas of the heart after CO

  5. Effect of chronic metoprolol and coronary occlusion (CO) on cardiac beta receptor density in cats

    Energy Technology Data Exchange (ETDEWEB)

    Lathers, C.M.; Spivey, W.H.; Levin, R.M.

    1986-03-05

    The effect of metoprolol (M) on beta receptor density (BRD) was examined. M (5 mg/kg, p.o., b.i.d.) was given for 2 and 8 wks prior to CO of the left anterior descending artery (LAD) at its origin. BRD, determined by binding of /sup 3/H-dihydroalprenol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal LAD distribution, LV = 2 distal LAD distribution, LV3 = posterior left ventricle, RV = right ventricle, and S = septum. A 2 factor ANOVA followed by simple effect and Newman-Keuls post hoc tests revealed that M produced no effect in BRD in LA, RA, LV2, or S. M increased BRD in LV1, LV3, and RV after 2 wk when compared to no M. In addition, BRD in LV3 and RV were also greater at 2 wk than after 8 wk M. The data indicate that there are regional differences in the beta adrenergic receptor densities among the areas of the heart and within the left ventricle. Chronic dosing with M produced increased BRD in only some of the areas of the heart. These differences may be related to functional differences in the various areas of the heart after CO.

  6. EFFECT OF ELECTROACUPUNCTURE ON MYOCARDIAL ISCHEMIA INDUCED CHANGES OF CARDIAC SYMPATHETIC ACTIVITY AND INVOLVEMENT OF SPINIAL δ-OPIOID,NMDA-AND NON-NMDA RECEPTORS IN THE RABBIT

    Institute of Scientific and Technical Information of China (English)

    刘俊岭; 高永辉; 陈淑萍

    2003-01-01

    Aim: To observe the effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) induced changes of cardiac sympathetic discharges and the effects of some related receptors in the spinal cord. Methods: A total of 53 rabbits anesthetized with mixture solution of 25% urethane (420 mg/kg) and 1.5% chloralose (50 mg/kg)were used in this study. AMI was induced by occlusion of the ventricular branch of the left coronary artery. Discharges of the left cardiac sympathetic nerve were recorded by using a bipolar platinum electrode. Bilateral "Ximen"(PC 40)and "Kongzhui"(LU 6) were stimulated electrically by using an EA therapeutic apparatus or an electrical stimulator.DPDPE δ-opiate receptor agonist, 20 nmol, 10 μL, n= 8), Naltrindole Hydrochloride (δ-opiate receptor antagonist, 20nmol, 10 μL, n=8), DAP5 (NMDA receptor antagonist, 5 nmol, 10 μL, n=9) and CNQX (non-NMDA receptor antagonist, 5 nmol, 10 μL, n=8) were respectively injected into the thoracic subarachnoid space of the spinal cord in different groups, followed by observing their effects on changes of sympathetic activity evoked by EA of the abovementioned acupoints. Results: ① After AMI, sympathetic discharges increased (200.56± 79.89%) in 10 cases and decreased (- 59.34 ±7.06% ) in other 9 cases in comparison with their individual basal values. After EA of "Ximen" (PC 4)and "Kongzhui" (Lu 6), AMI-induced increase and decrease changes of the sympathetic activity were suppressed significantly, but the effect of EA of LU-6 was weaker than that of EA of PC-4.②Following EA of PC-4 and LU-6, sympathetic discharges increased significantly in 2 and 4 cases, decreased apparently in 7 and 3 cases, and had no striking changes in 1 and 3 cases respectively. The mean reaction threshold of sympathetic activity after EA of PC-4 and LU-6were 2.1 ± 0.65 mA and 3.28± 1.13 mA separately.③ After pre-treatment with DPDPE, the reaction threshold of the cardiac sympathetic activity to EA of PC-4 elevated

  7. Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death.

    Science.gov (United States)

    Aiba, Isamu; Wehrens, Xander H T; Noebels, Jeffrey L

    2016-08-16

    Cardiorespiratory failure is the most common cause of sudden unexplained death in epilepsy (SUDEP). Genetic autopsies have detected "leaky" gain-of-function mutations in the ryanodine receptor-2 (RyR2) gene in both SUDEP and sudden cardiac death cases linked to catecholaminergic polymorphic ventricular tachycardia that feature lethal cardiac arrhythmias without structural abnormality. Here we find that a human leaky RyR2 mutation, R176Q (RQ), alters neurotransmitter release probability in mice and significantly lowers the threshold for spreading depolarization (SD) in dorsal medulla, leading to cardiorespiratory collapse. Rare episodes of sinus bradycardia, spontaneous seizure, and sudden death were detected in RQ/+ mutant mice in vivo; however, when provoked, cortical seizures frequently led to apneas, brainstem SD, cardiorespiratory failure, and death. In vitro studies revealed that the RQ mutation selectively strengthened excitatory, but not inhibitory, synapses and facilitated SD in both the neocortex as well as brainstem dorsal medulla autonomic microcircuits. These data link defects in neuronal intracellular calcium homeostasis to the vulnerability of central autonomic brainstem pathways to hypoxic stress and implicate brainstem SD as a previously unrecognized site and mechanism contributing to premature death in individuals with leaky RYR2 mutations. PMID:27482086

  8. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    International Nuclear Information System (INIS)

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence

  9. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L., E-mail: laorden@um.es

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  10. Temperature and species-specific effects on ß3-adrenergic receptor cardiac regulation in two freshwater teleosts: Channel catfish (Ictalurus punctatus) and common carp (Cyprinus carpio).

    Science.gov (United States)

    Petersen, L H; Burleson, M L; Huggett, D B

    2015-07-01

    β₃-adrenergic receptors (AR) are important in teleost cardiovascular regulation. To date, it is unknown whether temperature acclimation changes ß₃-AR functionality and consequently the involvement of this AR subtype in teleost cardiac regulation. Common carp (Cyprinus carpio) were acclimated at 12 °C or 23 °C (minimum 3 weeks) after which cardiovascular variables (cardiac output (Q), stroke volume (Sv) and heart rate (fH)) were measured upon injection of the ß₃-AR agonist, BRL(37344), and antagonist, SR(59230A). In both 12 °C and 23 °C acclimated carp, BRL(37344) induced significant increases in fH and Q whereas Sv was significantly decreased. While temperature did not affect the change (increase vs. decrease) in cardiac variables, the magnitude and on-set of responses differed. For instance, fH, Sv and Q responded significantly faster to ß₃-AR stimulation in 23 °C carp. In contrast, maximum responses of fH and Q were significantly higher in 23 °C carp whereas the maximum response of Sv was significantly greater in 12 °C carp. These findings suggest that temperature acclimation induced changes in β₃-AR receptor functionality (e.g. density and/or affinity). Stimulation of β₃-ARs in 23 °C acclimated channel catfish (Ictalurus punctatus) caused significant increases in fH, Sv and Q. The increase in Sv was opposite to the decrease observed in 23 °C acclimated common carp. SR(59230A) induced significant decreases in Sv and Q but had no effect in carp (23 °C). Results suggest species diversity in the density and affinity or structure of ß₃-ARs which may explain the different cardiac responses to ß₃-AR ligands. PMID:25882086

  11. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  12. Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    K. Peraza-Cruces

    2008-09-01

    Full Text Available The pathogenesis of chagasic cardiomyopathy is not completely understood, but it has been correlated with parasympathetic denervation (neurogenic theory and inflammatory activity (immunogenic theory that could affect heart muscarinic acetylcholine receptor (mAChR expression. In order to further understand whether neurogenic and/or immunogenic alterations are related to changes in mAChR expression, we studied two models of Trypanosoma cruzi infection: 1 in 3-week-old male Sprague Dawley rats chronically infected with T. cruzi and 2 isolated primary cardiomyocytes co-cultured with T. cruzi and peripheral blood mononuclear cells (PBMC. Using [³H]-quinuclidinylbenzilate ([³H]-QNB binding assays, we evaluated mAChR expression in homogenates from selected cardiac regions, PBMC, and cultured cardiomyocytes. We also determined in vitro protein expression and pro-inflammatory cytokine expression in serum and cell culture medium by ELISA. Our results showed that: 1 mAChR were significantly (P < 0.05 up-regulated in right ventricular myocardium (means ± SEM; control: 58.69 ± 5.54, N = 29; Chagas: 72.29 ± 5.79 fmol/mg, N = 34 and PBMC (control: 12.88 ± 2.45, N = 18; Chagas: 20.22 ± 1.82 fmol/mg, N = 19, as well as in cardiomyocyte transmembranes cultured with either PBMC/T. cruzi co-cultures (control: 24.33 ± 3.83; Chagas: 43.62 ± 5.08 fmol/mg, N = 7 for both or their conditioned medium (control: 37.84 ± 3.84, N = 4; Chagas: 54.38 ± 6.28 fmol/mg, N = 20; 2 [³H]-leucine uptake was increased in cardiomyocytes co-cultured with PBMC/T. cruzi-conditioned medium (Chagas: 21,030 ± 2321; control 10,940 ± 2385 dpm, N = 7 for both; P < 0.05; 3 plasma IL-6 was increased in chagasic rats, IL-1β, was increased in both plasma of chagasic rats and in the culture medium, and TNF-α level was decreased in the culture medium. In conclusion, our results suggest that cytokines are involved in the up-regulation of mAChR in chronic Chagas disease.

  13. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

    OpenAIRE

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-01

    Background A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Methods Male Tibetan minipigs were ...

  14. Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction

    OpenAIRE

    Ayach, Bilal B.; Yoshimitsu, Makoto; Dawood, Fayez; Sun, Mei; Arab, Sara; Chen, Manyin; HIGUCHI, KOJI; Siatskas, Christopher; Lee, Paul; Lim, Hilda; Zhang, Jane; Cukerman, Eva; Stanford, William L.; Medin, Jeffrey A; Liu, Peter P.

    2006-01-01

    Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem∕progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly eluci...

  15. A preliminary experimental study on the cardiac toxicity of glutamate and the role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Yan; ZHOU Lan; XU Hai-fei; YAN Li; DING Fan; HAO Wei; CAO Ji-min

    2013-01-01

    Background Monosodium L-glutamate (MSG) is a food flavour enhancer and its potential harmfulness to the heart remains controversial.We investigated whether MSG could induce cardiac arrhythmias and apoptosis via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.Methods Myocardial infarction (MI) was created by ligating the coronary artery and ventricular arrhythmias were monitored by electrocardiogram in the rat in vivo.Neonatal rat cardiomyocytes were isolated and cultured.Cell viability was estimated by 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay.Calcium mobilization was monitored by confocal microscopy.Cardiomyocyte apoptosis was evaluated by acridine orange staining,flow cytometry,DNA laddering,reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results MSG (i.v.) decreased the heart rate at 0.5 g/kg and serious bradycardia at 1.5 g/kg,but could not induce ventricular tachyarrhythmias in normal rats in vivo.In rats with acute MI in vivo,however,MSG (1.5 g/kg,i.v.) induced ventricular tachyarrhythmias and these arrhythmias could be prevented by blocking the AMPA and N-methyl-d-aspartate (NMDA) receptors.Selectively activating the AMPA or NMDA receptor induced ventricular tachyarrhythmias in MI rats.At the cellular level,AMPA induced calcium mobilization,oxidative stress,mitochondrial dysfunction and apoptosis in cultured cardiomyocytes,especially when the AMPA receptor desensitization were blocked by cyclothiazide.The above toxic cellular effects of AMPA were abolished by AMPA receptor blockade or by H2O2 scavengers.Conclusions MSG induces bradycardia in normal rats,but triggers lethal tachyarrhythmias in myocardial infarcted rats probably by hindering AMPA receptors.AMPA receptor overstimulation also induces cardiomyocyte apoptosis,which may facilitate arrhythmia.

  16. Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice.

    Science.gov (United States)

    Stobdan, Tsering; Zhou, Dan; Ao-Ieong, Eilleen; Ortiz, Daniel; Ronen, Roy; Hartley, Iain; Gan, Zhuohui; McCulloch, Andrew D; Bafna, Vineet; Cabrales, Pedro; Haddad, Gabriel G

    2015-08-18

    To better understand human adaptation to stress, and in particular to hypoxia, we took advantage of one of nature's experiments at high altitude (HA) and studied Ethiopians, a population that is well-adapted to HA hypoxic stress. Using whole-genome sequencing, we discovered that EDNRB (Endothelin receptor type B) is a candidate gene involved in HA adaptation. To test whether EDNRB plays a critical role in hypoxia tolerance and adaptation, we generated EdnrB knockout mice and found that when EdnrB (-/+) heterozygote mice are treated with lower levels of oxygen (O2), they tolerate various levels of hypoxia (even extreme hypoxia, e.g., 5% O2) very well. For example, they maintain ejection fraction, cardiac contractility, and cardiac output in severe hypoxia. Furthermore, O2 delivery to vital organs was significantly higher and blood lactate was lower in EdnrB (-/+) compared with wild type in hypoxia. Tissue hypoxia in brain, heart, and kidney was lower in EdnrB (-/+) mice as well. These data demonstrate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Transcriptomic profiling of left ventricles revealed three specific genes [natriuretic peptide type A (Nppa), sarcolipin (Sln), and myosin light polypeptide 4 (Myl4)] that were oppositely expressed (q < 0.05) between EdnrB (-/+) and wild type. Functions related to these gene networks were consistent with a better cardiac contractility and performance. We conclude that EDNRB plays a key role in hypoxia tolerance and that a lower level of EDNRB contributes, at least in part, to HA adaptation in humans. PMID:26240367

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

    Directory of Open Access Journals (Sweden)

    Bosch Fatima

    2011-06-01

    Full Text Available Abstract Background Lack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/-ApoB100/100. Methods and results 18-month-old LDLR-/-ApoB100/100 (n = 12, diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II (IGF-II in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14 and age-matched C57Bl/6 mice (n = 15 were studied after three months of high-fat Western diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100 mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60% and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80% despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion. Conclusions LDLR-/-ApoB100/100 mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals.

  18. Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

    Directory of Open Access Journals (Sweden)

    Goodchild Ann K

    2010-10-01

    Full Text Available Abstract Background Cardiac vagal preganglionic neurons (CVPN are responsible for the tonic, reflex and respiratory modulation of heart rate (HR. Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve. Results Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN. Conclusions We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.

  19. A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of the Short-Acting β1-Adrenergic Receptor Blocker Landiolol Hydrochloride for Coronary Computed Tomography Angiography in Japanese Patients with Suspected Ischemic Cardiac Disease

    OpenAIRE

    Hirano, Masaharu; Yamashina, Akira; Hara, Kazuhiro; Ikari, Yuji; Jinzaki, Masahiro; Iino, Misako; Yamaguchi, Takuhiro; Tanimoto, Mitsunobu; Kuribayashi, Sachio; ,

    2013-01-01

    Objectives and Background The objective of this study was to investigate the image quality-improving and heart rate-lowering effects of landiolol hydrochloride (a short-acting β1-adrenergic receptor blocker) on coronary computed tomography angiography (CCTA). During CCTA, β-adrenergic receptor blockers have been commonly used to lower heart rate and improve image quality. Methods A total of 258 subjects suspected of having ischemic cardiac disease and requiring CCTA were randomized to either ...

  20. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-Trong Minh; Williams, George S.B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  1. Comparison between effects of caffeine and ryanodine on electromechanical coupling in myocardium of hibernating chipmunks: role of internal Ca stores.

    OpenAIRE

    Kondo, N

    1988-01-01

    1. To clarify the cause of uncoupling of Ca influx through Ca channels and the contractility of the myocardium in hibernating chipmunks, the electromechanical effects of two different internal Ca store inhibitors, caffeine and ryanodine, and a cardiotonic agent, isoprenaline, were investigated in papillary muscles of hibernating animals. 2. Ryanodine (10(-6) M), an inhibitor of internal Ca release, abolished the contraction with a marked inhibition of the action potential plateau (APp). In su...

  2. In vivo transfer of soluble TNF-alpha receptor 1 gene improves cardiac function and reduces infarct size after myocardial infarction in rats.

    Science.gov (United States)

    Sugano, Masahiro; Tsuchida, Keiko; Hata, Tomoji; Makino, Naoki

    2004-05-01

    Increased circulating and cardiac TNF-alpha levels during myocardial ischemia have been found in both experimental animals and patients with ischemic heart disease and advanced heart failure. Soluble TNF-alpha receptor 1 (sTNFR1) is an antagonist to TNF-alpha. In the present study, we examined whether sTNFR1 improves cardiac function in rats after myocardial infarction. Male Wistar rats were subjected to left coronary artery (LCA) ligation. Immediately after the ligation, a total of 200 microg of either the sTNFR1 or LacZ plasmid was injected into three different sites in the left ventricular wall. From 1 to 21 days after LCA ligation, TNF-alpha bioactivity in the heart was higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase. The LV diastolic dimension was significantly lower, and the fractional shortening was significantly higher in rats treated with the sTNFR1 plasmid than in those treated with the LacZ plasmid. At 21 days after LCA ligation, the LV end-diastolic pressure was also significantly lower in the rats treated with the sTNFR1 plasmid. In addition, the sTNFR1 expression plasmid had significantly reduced the infarct size. In conclusion, TNF-alpha bioactivity in the heart increased during the early stage of infarction and remained elevated. This elevation seemed partially responsible for the impairment of LV function and the increased infarct size. Suppression of TNF-alpha bioactivity from the early stage of infarction with the sTNFR1 plasmid improved cardiac function and reduced infarct size. PMID:15117889

  3. Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

    DEFF Research Database (Denmark)

    Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle;

    2015-01-01

    Electrocardiography is an important method for evaluation and risk stratification of patients with cardiac hypertrophy. We hypothesized that the recently developed transgenic mouse model of cardiac hypertrophy (ErbB2(tg)) will display distinct ECG features, enabling WT (wild type) mice to be......, the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG...... distinguished from transgenic mice without using conventional PCR genotyping. We evaluated more than 2000 mice and developed specific criteria for genotype determination by using cageside ECG, during which unanesthetized mice were manually restrained for less than 1 min. Compared with those from WT counterparts...

  4. Calpain Activity and Toll-Like Receptor 4 Expression in Platelet Regulate Haemostatic Situation in Patients Undergoing Cardiac Surgery and Coagulation in Mice

    Directory of Open Access Journals (Sweden)

    Jui-Chi Tsai

    2014-01-01

    Full Text Available Human platelets express Toll-like receptors (TLR 4. However, the mechanism by which TLR4 directly affects platelet aggregation and blood coagulation remains to be explored. Therefore, in this study, we evaluated the platelet TLR4 expression in patients who underwent CABG surgery; we explored the correlation between platelet TLR4 expression and the early outcomes in hospital of patients. Additionally, C57BL/6 and C57BL/6-TlrLPS−/− mice were used to explore the roles of platelet TLR4 in coagulation by platelet aggregometry and rotation thromboelastometry. In conclusion, our results highlight the important roles of TLR4 in blood coagulation and platelet function. Of clinical relevance, we also explored novel roles for platelet TLR4 that are associated with early outcomes in cardiac surgery.

  5. Prolonged TSH receptor A subunit immunization of female mice leads to a long-term model of Graves' disease, tachycardia, and cardiac hypertrophy.

    Science.gov (United States)

    Holthoff, Hans-Peter; Goebel, Sylvia; Li, Zhongmin; Faßbender, Julia; Reimann, Andreas; Zeibig, Stefan; Lohse, Martin J; Münch, Götz; Ungerer, Martin

    2015-04-01

    A transient model for human Graves' disease was successfully established in mice using up to 3 immunizations with recombinant adenovirus expressing the extracellular A-subunit of the human TSH receptor (TSHR) (Ad-TSHR). We studied extension of adenovirally induced TSHR A-subunit immunization in mice by using a novel protocol of long-term 3- and 4-weekly injections. Generation of TSHR binding stimulatory antibodies (capacity to stimulate cAMP activity in TSHR-expressing test cells), goiter, and histological thyroid alterations were maintained for at least 9 months in all Ad-TSHR-immunized mice. In response to injection of 10(10) plaque-forming units of Ad-TSHR, also elevated mean serum T4 levels were observed throughout the study. Moreover, cardiac organ involvement (tachycardia and hypertrophy) were consistently observed in these mice. Higher doses of Ad-TSHR (10(11) plaque-forming units) did not produce consistent elevation of T4 and were not associated with a clear increase in heart rate vs controls, probably because these high doses provoked an immune response-induced tachycardia on their own. In summary, a long-term model of Graves' disease induced by a relatively simple protocol of continuing monthly immunizations should allow to investigate long-term disease mechanisms and may possibly obviate the need for more complicated disease models. Moreover, the clinical outcome predictor of tachycardia and cardiac involvement was reliably detected in the model. PMID:25562617

  6. Cardiac peroxisome proliferator-activated receptor-γ expression is modulated by oxidative stress in acutely infrasound-exposed cardiomyocytes.

    Science.gov (United States)

    Pei, Zhaohui; Meng, Rongsen; Zhuang, Zhiqiang; Zhao, Yiqiao; Liu, Fangpeng; Zhu, Miao-Zhang; Li, Ruiman

    2013-12-01

    The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ. PMID:23632742

  7. High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin

    OpenAIRE

    Saris, Jasper; Derkx, Frans; Bruin, René; Dekkers, Dick; Lamers, Jos; Saxena, Pramod Ranjan; Schalekamp, Maarten; Danser, Jan

    2001-01-01

    textabstractMannose-6-phosphate (man-6-P)/insulin-like growth factor-II (man-6-P/IgF-II) receptors are involved in the activation of recombinant human prorenin by cardiomyocytes. To investigate the kinetics of this process, the nature of activation, the existence of other prorenin receptors, and binding of native prorenin, neonatal rat cardiomyocytes were incubated with recombinant, renal, or amniotic fluid prorenin with or without man-6-P. Intact and activated prorenin were measured in cell ...

  8. Constitutive inhibitory action of muscarinic receptors on adenylyl cyclase in cardiac membranes and its stereospecific suppression by hyoscyamine

    Czech Academy of Sciences Publication Activity Database

    Říčný, Jan; Gualtieri, F.; Tuček, Stanislav

    2002-01-01

    Roč. 51, č. 2 (2002), s. 131-137. ISSN 0862-8408 R&D Projects: GA AV ČR IAA7011910; GA ČR GA309/99/0214 Institutional research plan: CEZ:AV0Z5011922 Keywords : muscarinic receptors * adenylyl cyclase * constitutive activity of receptors Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 0.984, year: 2002

  9. Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

    Directory of Open Access Journals (Sweden)

    Ojaimi Caroline

    2010-08-01

    Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

  10. Preserved cardiac mitochondrial function and reduced ischaemia/reperfusion injury afforded by chronic continuous hypoxia: Role of opioid receptors

    Czech Academy of Sciences Publication Activity Database

    Maslov, L. N.; Naryzhnaya, N. V.; Prokudina, E. S.; Kolář, František; Gorbunov, A. S.; Zhang, Y.; Wang, H.; Tsibulnikov, S.Yu.; Portnichenko, A. G.; Lasukova, T. V.; Lishmanov, Yu. B.

    2015-01-01

    Roč. 42, č. 5 (2015), s. 496-501. ISSN 1440-1681 R&D Projects: GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : cardioprotection * chronic hypoxia * ischaemia/reperfusion * mitochondrial function * opioid receptors Subject RIV: ED - Physiology Impact factor: 2.372, year: 2014

  11. Cardiac hypertrophy induced by exercise training:the function of AT1 receptor, autophagy and miRNAs%运动性心脏肥大:AT1受体、细胞自噬和 miRNAs 的调节

    Institute of Scientific and Technical Information of China (English)

    钱帅伟; 张瑞萍; 张安民

    2014-01-01

    As a mechanical and exogenous stimulus , exercise training induces cardiac physiological hypertro-phy, and the cardiac structure is changed slowly , steadily and coordinately.Simultaneously, energy metabolism and func-tion of the cardiac muscle are also improved .These are positive adaptations in the heart when experiencing endurance exer -cise training.Recently, angiotensinⅡtype 1 (AT1) receptor, autophagy and miRNAs are all considered as important reg-ulators to cardiac hypertrophy induced by exercise training at different molecular levels .Fully understanding the relations and the important role of AT1 receptor, autophagy and miRNAs in cardiac physiological hypertrophy will further enrich the signaling pathway of cardiac hypertrophy induced by exercise training .

  12. Disease: H01019 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available y mutations in the cardiac ryanodine receptor gene (RYR2) accounting for an autosomal dominant form (CPVT1) ...or mutations in the cardiac calsequestrin gene CASQ2 accounting for an autosomal recessive form (CPVT2). It

  13. Hypoxia and glucose independently regulate the beta-adrenergic receptor-adenylate cyclase system in cardiac myocytes.

    OpenAIRE

    Rocha-Singh, K J; Honbo, N Y; Karliner, J S

    1991-01-01

    We explored the effects of two components of ischemia, hypoxia and glucose deprivation, on the beta-adrenergic receptor (beta AR)-adenylate cyclase system in a model of hypoxic injury in cultured neonatal rat ventricular myocytes. After 2 h of hypoxia in the presence of 5 mM glucose, cell surface beta AR density (3H-CGP-12177) decreased from 54.8 +/- 8.4 to 39 +/- 6.3 (SE) fmol/mg protein (n = 10, P less than 0.025), while cytosolic beta AR density (125I-iodocyanopindolol [ICYP]) increased by...

  14. 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.

  15. Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development

    Energy Technology Data Exchange (ETDEWEB)

    Incardona, John P., E-mail: john.incardona@noaa.gov; Linbo, Tiffany L.; Scholz, Nathaniel L.

    2011-12-15

    Petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs), commonly occur as complex mixtures in the environment. Recent studies using the zebrafish experimental model have shown that PAHs are toxic to the embryonic cardiovascular system, and that the severity and nature of this developmental cardiotoxicity varies by individual PAH. In the present study we characterize the toxicity of the relatively higher molecular weight 5-ring PAHs benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and benzo[k]fluoranthene (BkF). While all three compounds target the cardiovascular system, the underlying role of the ligand-activated aryl hydrocarbon receptor (AHR2) and the tissue-specific induction of the cytochrome p450 metabolic pathway (CYP1A) were distinct for each. BaP exposure (40 {mu}M) produced AHR2-dependent bradycardia, pericardial edema, and myocardial CYP1A immunofluorescence. By contrast, BkF exposure (4-40 {mu}M) caused more severe pericardial edema, looping defects, and erythrocyte regurgitation through the atrioventricular valve that were AHR2-independent (i.e., absent myocardial or endocardial CYP1A induction). Lastly, exposure to BeP (40 {mu}M) yielded a low level of CYP1A+ signal in the vascular endothelium of the head and trunk, without evident toxic effects on cardiac function or morphogenesis. Combined with earlier work on 3- and 4-ring PAHs, our findings provide a more complete picture of how individual PAHs may drive the cardiotoxicity of mixtures in which they predominate. This will improve toxic injury assessments and risk assessments for wild fish populations that spawn in habitats altered by overlapping petroleum-related human impacts such as oil spills, urban stormwater runoff, or sediments contaminated by legacy industrial activities. -- Highlights: Black-Right-Pointing-Pointer PAH compounds with 5 rings in different arrangements caused differential tissue-specific patterns of CYP1A induction in zebrafish embryos. Black

  16. Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System.

    Science.gov (United States)

    Buwa, Chhabildas C; Mahajan, Umesh B; Patil, Chandragouda R; Goyal, Sameer N

    2016-07-01

    Apigenin (AP) is a flavone in dietary flavonoids reported as strong antioxidant and elite modulator of PPARγ. The current study evaluated the consequence of AP in isoproterenol (ISO)-induced oxidative stress and myocardial infarction during β-adrenergic receptor stimulus in rats by persistent hemodynamic, biochemical and histopathological changes. Rats received AP (25, 50 and 75 mg/kg/day) or vehicle i.p. for 14 days and ISO (100 mg/kg, s.c.) on 13th and 14th days for initiation of cardiotoxicity. ISO-treated rats showed evidence of significant dwindle in systolic and diastolic arterial pressures, maximal positive rate of developed left ventricular pressure. In totting up, a noteworthy diminution in activities of creatine kinase-MB isoenzyme, reduced glutathione, superoxide dismutase, catalase and level along with rise in malondialdehyde content were observed. The shielding function of AP on isoproterenol-induced myocardial damage was observed by attenuating all the endogenous parameters and the membrane-bound enzymes. It was confirmed by histopathological examinations. The effect of AP at the doses of 50 and 75 mg/kg showed added apparent than at the dose of 25 mg/kg. Current study thus provides confirmation for protective effects of AP on myocardium in experimentally induced myocardial infarction. PMID:26186996

  17. Phosphatidylinositol 4,5-biphosphate (PIP2) modulates syntaxin-1A binding to sulfonylurea receptor 2A to regulate cardiac ATP-sensitive potassium (KATP) channels.

    Science.gov (United States)

    Xie, Li; Liang, Tao; Kang, Youhou; Lin, Xianguang; Sobbi, Roozbeh; Xie, Huanli; Chao, Christin; Backx, Peter; Feng, Zhong-Ping; Shyng, Show-Ling; Gaisano, Herbert Y

    2014-10-01

    Cardiac sarcolemmal syntaxin (Syn)-1A interacts with sulfonylurea receptor (SUR) 2A to inhibit ATP-sensitive potassium (KATP) channels. Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous endogenous inositol phospholipid, known to bind Kir6.2 subunit to open KATP channels, has recently been shown to directly bind Syn-1A in plasma membrane to form Syn-1A clusters. Here, we sought to determine whether the interaction between Syn-1A and PIP2 interferes with the ability of Syn-1A to bind SUR2A and inhibit KATP channel activity. We found that PIP2 dose-dependently reduced SUR2A binding to GST-Syn-1A by in vitro pulldown assays. FRET studies in intact cells using TIRFM revealed that increasing endogenous PIP2 levels led to increased Syn-1A (-EGFP) cluster formation and a severe reduction in availability of Syn-1A molecules to interact with SUR2A (-mCherry) molecules outside the Syn-1A clusters. Correspondingly, electrophysiological studies employing SUR2A/Kir6.2-expressing HEK cells showed that increasing endogenous or exogenous PIP2 diminished the inhibitory effect of Syn-1A on KATP currents. The physiological relevance of these findings was confirmed by ability of exogenous PIP2 to block exogenous Syn-1A inhibition of cardiac KATP currents in inside-out patches of mouse ventricular myocytes. The effect of PIP2 on physical and functional interactions between Syn-1A and KATP channels is specific and not observed with physiologic concentrations of other phospholipids. To unequivocally demonstrate the specificity of PIP2 interaction with Syn-1A and its impact on KATP channel modulation by Syn-1A, we employed a PIP2-insensitive Syn-1A-5RK/A mutant. The Syn-1A-5RK/A mutant retains the ability to interact with SUR2A in both in vitro binding and in vivo FRET assays, although as expected the interaction is no longer disrupted by PIP2. Interestingly, at physiological PIP2 concentrations, Syn-1A-5RK/A inhibited KATP currents to a greater extent than Syn-1A-WT, indicating

  18. 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

  19. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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...

  4. Impact of detubulation on force and kinetics of cardiac muscle contraction.

    Science.gov (United States)

    Ferrantini, Cecilia; Coppini, Raffaele; Sacconi, Leonardo; Tosi, Benedetta; Zhang, Mei Luo; Wang, Guo Liang; de Vries, Ewout; Hoppenbrouwers, Ernst; Pavone, Francesco; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado; ter Keurs, Henk E D J

    2014-06-01

    Action potential-driven Ca(2+) currents from the transverse tubules (t-tubules) trigger synchronous Ca(2+) release from the sarcoplasmic reticulum of cardiomyocytes. Loss of t-tubules has been reported in cardiac diseases, including heart failure, but the effect of uncoupling t-tubules from the sarcolemma on cardiac muscle mechanics remains largely unknown. We dissected intact rat right ventricular trabeculae and compared force, sarcomere length, and intracellular Ca(2+) in control trabeculae with trabeculae in which the t-tubules were uncoupled from the plasma membrane by formamide-induced osmotic shock (detubulation). We verified disconnection of a consistent fraction of t-tubules from the sarcolemma by two-photon fluorescence imaging of FM4-64-labeled membranes and by the absence of tubular action potential, which was recorded by random access multiphoton microscopy in combination with a voltage-sensitive dye (Di-4-AN(F)EPPTEA). Detubulation reduced the amplitude and prolonged the duration of Ca(2+) transients, leading to slower kinetics of force generation and relaxation and reduced twitch tension (1 Hz, 30°C, 1.5 mM [Ca(2+)]o). No mechanical changes were observed in rat left atrial trabeculae after formamide shock, consistent with the lack of t-tubules in rodent atrial myocytes. Detubulation diminished the rate-dependent increase of Ca(2+)-transient amplitude and twitch force. However, maximal twitch tension at high [Ca(2+)]o or in post-rest potentiated beats was unaffected, although contraction kinetics were slower. The ryanodine receptor (RyR)2 Ca-sensitizing agent caffeine (200 µM), which increases the velocity of transverse Ca(2+) release propagation in detubulated cardiomyocytes, rescued the depressed contractile force and the slower twitch kinetics of detubulated trabeculae, with negligible effects in controls. We conclude that partial loss of t-tubules leads to myocardial contractile abnormalities that can be rescued by enhancing and accelerating the

  5. 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

  6. A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene.

    Science.gov (United States)

    Li, Zuoqing; Yang, Neng; Zhou, Ling; Gu, Peng; Wang, Hui; Zhou, Yun; Zhou, Peijun; Lu, Liming; Chou, Kuang-Yen

    2016-03-01

    The plant protein trichosanthin (Tk) and its derived peptide tetramer Tk-tPN have been shown to stimulate the type 2 immune responses for treating autoimmune disease. This work explores the possibility of using Tk-tPN as a non-toxic immunosuppressant to induce transplantation tolerance using the mechanisms by which T-cell-mediated immune responses are transferred from type 1 to type 2 through innate immunity-related pathways. Immunocytes and cytokine secretions involved in the mouse cardiac allografting model with Tk-tPN treatment were characterized. Identification of critical genes and analysis of their functions through Toll-like receptor (TLR) -initiated signalling and the possible epigenetic changes were performed. Mean survival times of the cardiac allografts were delayed from 7·7 ± 0·3 days (control) to 22·7 ± 3·9 days (P Gata3(+) ), together with a selective expansion of the IL-4/IL-10-producing CD8(+)  CD28(-) regulatory T-cell subset. A TLR2-initiated high expression of chemokine gene MCP1 was detectable simultaneously. Epigenetically Tk/Tk-tPN could also acetylate the histone H3K9 of MCP1 promoter to skew the immunity towards T helper type 2 responses. Tk/Tk-tPN is therefore capable of down-regulating the type 1 response-dominant rejection of cardiac allografts by evoking type 2 immunity through the activation of a TLR2-initiated signalling pathway and MCP1 gene to expand the IL-4/IL-10-secreting CD8(+)  CD28(-) regulatory T cells. Tk-tPN could be a promising novel immunosuppressant to induce tolerance in allotransplantation. PMID:26694804

  7. 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.)

  8. 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.

  9. Changes in cardiac glycoside receptor sites 86 rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation

    International Nuclear Information System (INIS)

    Measurements of the binding of 12-α-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86Rb uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. During the first few days of treatment [3H]-digoxin binding and 86Rb uptake fall and intraerythrocytic sodium concentrations rise. Subsequently parallel fluctuations occur in [3H]-digoxin binding and 86Rb uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS2I. Plasma digoxin concentrations do not correlate with QS2I. (author)

  10. 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

  11. 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.

  12. Endothelin A Receptor Antagonist, Atrasentan, Attenuates Renal and Cardiac Dysfunction in Dahl Salt-Hypertensive Rats in a Blood Pressure Independent Manner

    OpenAIRE

    Samad, Mohammed A.; Kim, Ui Kyoung; Kang, Joshua J.; Ke, Qingen; Kang, Peter M.

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist...

  13. 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

  14. Reversal of isoproterenol-induced downregulation of phospholamban and FKBP12.6 by CPU0213-mediated antagonism of endothelin receptors

    Institute of Scientific and Technical Information of China (English)

    Yu FENG; Xiao-yun TANG; De-zai DAI; Yin DAI

    2007-01-01

    Aim:The downregulation of phospholamban (PLB) and FKBPI 2.6 as a result of βreceptor activation is involved in the pathway(s) of congestive heart failure. We hypothesized that the endothelin (ET)-I system may link to downregulated PLB and FKBP12.6. Methods:Rats were subjected to ischemia/reperfusion (I/R) to cause heart failure (HF). 1 mg/kg isoproterenol (ISO) was injected subcutaneously (sc) for 10 d to worsen HF. 30 mg/kg CPU0213 (sc),a dual ET receptor (ETAR/ETBR) antagonist was given from d 6 to d 10. On d 11,cardiac function was assessed together with the determination of mRNA levels of ryanodine receptor 2,calstabin-2 (FKBP12.6),PLB,and sarcoplasmic reticulum Ca2+-ATPase. Isolated adult rat ventricular myocytes were incubated with ISO at lx 10-6 mol/L to set up an in vitro model of HF. Propranolol (PRO),CPU0213,and darusentan (DAR,an ETAR antagonist) were incubated with cardiomyocytes at 1 x 10.5 mol/L or 1 × 10-6mol/L in the presence of ISO (1× 10.6 mol/L). Immunocytochemistry and Western blotting were applied for measuring the protein levels of PLB and FKBP12.6.Results:The worsened hemodynamics produced by I/R were exacerbated by ISO pretreatment. The significant downregulation of the gene expression of PLB and FKBPI 2.6 and worsened cardiac function by ISO were reversed by CPU0213. In vitro ISO lx 10-6 mol/L produced a sharp decline of PLB and FKBP12.6 proteins relative to the control. The downregulation of the protein expression was significantly reversed by the ET receptor antagonist CPU0213 or DAR,comparable to that achieved by PRO. Conclusion:This study demonstrates a role of ET in mediating the downregulation of the cardiac Ca2+-handling protein by ISO.AcknowledgementWe are most grateful to Prof David J TRIGGLE from the State University of New York at Buffalo for assistance in revising the English of the manuscript.

  15. 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...

  16. 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.

  17. 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...

  18. 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

  19. Structure Activity Relationship of (N)-Methanocarba Phosphonate Analogues of 5’-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor

    OpenAIRE

    Kumar, T. Santhosh; Zhou, Si-yuan; Joshi, Bhalchandra V.; Balasubramanian, Ramachandran; Yang, Tiehong; Liang, Bruce T.; Jacobson, Kenneth A.

    2010-01-01

    P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis–Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (...

  20. 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 ...

  1. A role for peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) in the regulation of cardiac mitochondrial phospholipid biosynthesis.

    Science.gov (United States)

    Lai, Ling; Wang, Miao; Martin, Ola J; Leone, Teresa C; Vega, Rick B; Han, Xianlin; Kelly, Daniel P

    2014-01-24

    The energy demands of the adult mammalian heart are met largely by ATP generated via oxidation of fatty acids in a high capacity mitochondrial system. Peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-α and -β serve as inducible transcriptional coregulators of genes involved in mitochondrial biogenesis and metabolism. Whether PGC-1 plays a role in the regulation of mitochondrial structure is unknown. In this study, mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ(-/-)) in adult heart were analyzed. PGC-1αβ(-/-) hearts exhibited a distinctive mitochondrial cristae-stacking abnormality suggestive of a phospholipid abnormality as has been described in humans with genetic defects in cardiolipin (CL) synthesis (Barth syndrome). A subset of molecular species, containing n-3 polyunsaturated species in the CL, phosphatidylcholine, and phosphatidylethanolamine profiles, was reduced in PGC-1αβ-deficient hearts. Gene expression profiling of PGC-1αβ(-/-) hearts revealed reduced expression of the gene encoding CDP-diacylglycerol synthase 1 (Cds1), an enzyme that catalyzes the proximal step in CL biosynthesis. Cds1 gene promoter-reporter cotransfection experiments and chromatin immunoprecipitation studies demonstrated that PGC-1α coregulates estrogen-related receptors to activate the transcription of the Cds1 gene. We conclude that the PGC-1/estrogen-related receptor axis coordinately regulates metabolic and membrane structural programs relevant to the maintenance of high capacity mitochondrial function in heart. PMID:24337569

  2. 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

  3. Exercício de força ativa a via AKT/mTor pelo receptor de angiotensina II tipo I no músculo cardíaco de ratos Activation of AKT-mTor signaling pathways by angiotensin II receptor type 1 after a session of strength exercise in cardiac muscle of rats

    Directory of Open Access Journals (Sweden)

    Stéphano Freitas Soares Melo

    2011-09-01

    Full Text Available O receptor de angiotensina II tipo I (AT1 tem uma importante participação no desenvolvimento da hipertrofia cardíaca. Em um trabalho publicado anteriormente, por nosso grupo, demonstramos que o bloqueio do receptor AT1 durante o treinamento de força inibiu a hipertrofia cardíaca em ratos. Por isso, o objetivo deste trabalho foi estudar a participação do receptor AT1 na ativação de vias de sinalização intracelular relacionadas com o aumento da síntese de proteína em ratos submetidos a uma sessão de exercício de força. Para isso, realizamos um experimento com seis grupos de animais (n = 6; cada: controle (Con, exercitado e sacrificado cinco minutos após o exercício (Exe 5, exercitado e sacrificado 30 minutos após o exercício (Exe 30, controle tratado com losartan (Con Los, tratado com losartan, exercitado e sacrificado cinco minutos após o exercício (Exe 5 Los, tratado com losartan, exercitado e sacrificado 30 minutos após o exercício (Exe 30 Los. Os resultados mostram que no grupo Exe 5 e Exe 30 ocorreu um aumento de 63% (P The angiotensin II type I (AT1 receptor has an important participation in the development of cardiac hypertrophy. Previously, we have shown that AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats. Here, we studied the involvement of AT1 receptor in the activation of intracellular signaling pathways related to the concentric HC in rats submitted to a session of strength exercise. Male Wistar rats were divided into 6 groups (n= 6 each: control (Con; exercised and killed 5 minutes after exercise (Exe 5; exercised and killed 30 minutes after exercise (Exe 30; control treated with Losartan (Con Los; treated with Losartan, exercised and killed 5 minutes after the exercise (Exe Los 5; treated with Losartan, exercised and killed 30 minutes after training (Exe Los 30. The results show that phosphorylation activity of AKT in group Exe 5 and Exe 30 increased 63% (P < 0

  4. Muscarinic and nicotinic ACh receptor activation differentially mobilize Ca2+ in rat intracardiac ganglion neurons.

    Science.gov (United States)

    Beker, Friederike; Weber, Martin; Fink, Rainer H A; Adams, David J

    2003-09-01

    The origin of intracellular Ca2+ concentration ([Ca2+]i) transients stimulated by nicotinic (nAChR) and muscarinic (mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+]i increases that were reduced to approximately 60% of control in the presence of either atropine (1 microM) or mecamylamine (3 microM) and to <20% in the presence of both antagonists. Removal of external Ca2+ reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+]i response was reduced to 50% by 10 microM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+ release from ryanodine-sensitive Ca2+ stores may only contribute to the nAChR-induced [Ca2+]i responses. Perforated-patch whole cell recording at -60 mV shows that the rise in [Ca2+]i is concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+]i and membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons. PMID:12761283

  5. 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

  6. Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.

    Science.gov (United States)

    Panama, Brian K; Korogyi, Adam S; Aschar-Sobbi, Roozbeh; Oh, Yena; Gray, Charles B B; Gang, Hongying; Brown, Joan Heller; Kirshenbaum, Lorrie A; Backx, Peter H

    2016-02-19

    The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation. PMID:26742842

  7. Combination of miRNA499 and miRNA133 exerts a synergic effect on cardiac differentiation.

    Science.gov (United States)

    Pisano, Federica; Altomare, Claudia; Cervio, Elisabetta; Barile, Lucio; Rocchetti, Marcella; Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Copes, Francesco; Mura, Manuela; Danieli, Patrizia; Viarengo, Gianluca; Zaza, Antonio; Gnecchi, Massimiliano

    2015-04-01

    Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation. We used mouse P19 cells as a cardiogenic differentiation model. miRNA499, miRNA1, or miRNA133 were transiently over-expressed in P19 cells individually or in different combinations. The over-expression of miRNA499 alone increased the number of beating cells and the association of miRNA499 with miRNA133 exerted a synergistic effect, further increasing the number of beating cells. Real-time polymerase chain reaction showed that the combination of miRNA499 + 133 enhanced the expression of cardiac genes compared with controls. Western blot and immunocytochemistry for connexin43 and cardiac troponin T confirmed these findings. Importantly, caffeine responsiveness, a clear functional parameter of cardiac differentiation, was increased by miRNA499 in association with miRNA133 and was directly correlated with the activation of the cardiac troponin I isoform promoter. Cyclic contractions were reversibly abolished by extracellular calcium depletion, nifedipine, ryanodine, and IP3R blockade. Finally, we demonstrated that the use of miRNA499 + 133 induced cardiac differentiation even in the absence of dimethyl sulfoxide. Our results show that the areas spontaneously contracting possess electrophysiological and pharmacological characteristics compatible with true cardiac excitation-contraction coupling. The translational relevance of our findings was reinforced by the demonstration that the over-expression of miRNA499 and miRNA133 was also able to induce the differentiation of human mesenchymal stromal cells toward the cardiac lineage. PMID:25534971

  8. 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.

  9. 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 ...

  10. 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

  11. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    ZENG QingHua; LI XingTing; ZHONG GuoGan; ZHANG WenJie; SUN ChengWen

    2009-01-01

    Using fura-2-acetoxymethyl eater (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]1) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats.The effect of ET-1 on [Ca2+]1 elevation was abolished in the presence of the ETA receptor blocker BQ123,but was not affected by the ETa receptor blocker BQ788. ET-1-induced an increase in [Ca2+]1, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibltors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an Increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETa receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  12. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  13. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    OpenAIRE

    Drosatos, Konstantinos

    2016-01-01

    Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, ...

  14. Changes in mRNA levels of cardiac α1-adrenergic receptor and angiotensin Ⅱ receptor subtypes with aging in rats%大鼠心脏α1-肾上腺素受体和血管紧张素Ⅱ受体亚型mRNA水平的增龄改变

    Institute of Scientific and Technical Information of China (English)

    曹晓菁; 李艳芳

    2008-01-01

    Objective To examine the expression levels of α1-adrenergie receptor(α1-AR)and angiotensinⅡ reeeptor(ATR)subtypes in left ventricle of rats from adolescent age, middle age,presenium to senium. Methods Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantitate the messenger RNA (mRNA) of α1-AR and ATR subtypes in left ventricle in Wistar rats aged 3-months (adolescent age), 12-months (middle age), 18-months (presenium) and 24-months (senium). Results The expression of α1A-AR mRNA was decreased gradually with aging, and the gene expression of α1 D-AR was repressed in middle age and presenium,while the expression of a,B-AR mRNA remained unchanged during senescence. Cardiac AT1R expression was not affected by aging from adolescent age to presenium, but exhibited a remarkable up-regulation in senium There was no significant discrepancies of cardiac AT2R expression among the four different age groups. Conclusions The results suggest that there are considerable changes in mRNA levels of cardiac α1-AR and ATR subtypes with aging. The change of cardiac α1-AR and ATR expression during aging is a protective response for senescence and has an important significance in maintaining normal physiological functions of heart.%目的 从受体信使RNA(messenger RNA,mRNA)水平研究了心脏α1-肾上腺素受体(α1-AR)亚型和血管紧张素Ⅱ受体(ATR)亚型在大鼠增龄过程中表达水平的变化. 方法 采用半定量逆转录聚合酶链反应(semiquantitative reverse transcription polymerase chain reaction,RTPCR)分别对3月龄(青年)、12月龄(中年)、18月龄(老年前期)和24月龄(老年)Wistar大鼠左心室的mRNA水平进行测定. 结果 α1A-AR随增龄逐渐F调,各年龄组的表达水平分别为0.71±0.06、0.29±0.06、0.23±0.03、0.12±0.04.α1D-AR在中年和老年前期下凋,各年龄组的表达水平分别为0.52±0.05、0.41±0.03、0.24±0.11、0.27±0.08.α1B-AR的表达未

  15. 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.

  16. Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons.

    Science.gov (United States)

    Weber, Martin; Motin, Leonid; Gaul, Simon; Beker, Friederike; Fink, Rainer H A; Adams, David J

    2005-01-01

    The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca(2+) concentration ([Ca(2+)](i)) and membrane currents were investigated in neonatal rat intracardiac neurons. In fura-2-loaded neurons, nAChR activation evoked a transient increase in [Ca(2+)](I), which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half-maximal concentration for thiopental inhibition of nAChR-induced [Ca(2+)](i) transients was 28 microM, close to the estimated clinical EC(50) (clinically relevant (half-maximal) effective concentration) of thiopental. In fura-2-loaded neurons, voltage clamped at -60 mV to eliminate any contribution of voltage-gated Ca(2+) channels, thiopental (25 microM) simultaneously inhibited nAChR-induced increases in [Ca(2+)](i) and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by approximately 40% at -120, -80 and -40 mV holding potential, indicating that the inhibition is voltage independent. The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC(50) were also shown to inhibit nAChR-induced increases in [Ca(2+)](i) by approximately 40%. Thiopental (25 muM) did not inhibit caffeine-, muscarine- or ATP-evoked increases in [Ca(2+)](i), indicating that inhibition of Ca(2+) release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely. Depolarization-activated Ca(2+) channel currents were unaffected in the presence of thiopental (25 microM), pentobarbital (50 microM) and ketamine (10 microM). In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and [Ca(2+)](i) transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions. PMID:15644873

  17. 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.

  18. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  19. 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...

  20. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    OpenAIRE

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

  1. Thyroid Hormone Control of Cardiac Substrate Metabolism

    OpenAIRE

    Hyyti Villet, Outi

    2009-01-01

    Thyroid hormone (TH) plays an important role in maintaining a homeostasis in all the cells of our body. It also has significant cardiovascular effects, and abnormalities of its concentration can cause cardiovascular disease and even morbidity. Especially development of heart failure has been connected to low levels of thyroid hormone. A decrease in TH levels or TH-receptor binding adversely effects cardiac function. Although, this occurs in part through alterations in excitation-contraction a...

  2. Cardiac cAMP: production, hydrolysis, modulation and detection.

    Science.gov (United States)

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  3. Abnormal cardiac autonomic regulation in mice lacking ASIC3.

    Science.gov (United States)

    Cheng, Ching-Feng; Kuo, Terry B J; Chen, Wei-Nan; Lin, Chao-Chieh; Chen, Chih-Cheng

    2014-01-01

    Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases. PMID:24804235

  4. Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng

    2014-01-01

    Full Text Available Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3 is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

  5. AT1 receptors as mechanosensors.

    Science.gov (United States)

    Mederos y Schnitzler, Michael; Storch, Ursula; Gudermann, Thomas

    2011-04-01

    G-protein-coupled receptors are appreciated as central components of neurohormonal signaling. Recently, it turned out that they may also play a role in mechanotransduction. The angiotensin II AT(1) receptor was the first G-protein-coupled receptor claimed to be a mechanosensor. In the meantime, several other G(q/11)-coupled receptors were found to be sensitive to mechanical stimuli. Furthermore, there is first evidence to support the concept that G(i/o)-coupled receptors are susceptible to mechanical stimulation as well. Mechanical receptor activation appears to be agonist-independent and is initiated by a conformational change of the receptor protein discernible from agonist-bound conformations. Mechanically induced receptor activation plays a physiological role for myogenic vasoconstriction and is involved in the pathogenesis of cardiac hypertrophy. PMID:21147033

  6. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells

    International Nuclear Information System (INIS)

    Extracellular Ca2+ concentration ([Ca2+]o) regulates the functions of many cell types through a G protein-coupled [Ca2+]o-sensing receptor (CaR). Whether the receptor is functionally expressed in vascular endothelial cells is largely unknown. In cultured human aortic endothelial cells (HAEC), RT-PCR yielded the expected 555-bp product corresponding to the CaR, and CaR protein was demonstrated by fluorescence immunostaining and Western blot. RT-PCR also demonstrated the expression in HAEC of alternatively spliced variants of the CaR lacking exon 5. Although stimulation of fura 2-loaded HAEC by several CaR agonists (high [Ca2+]o, neomycin, and gadolinium) failed to increase intracellular Ca2+ concentration ([Ca2+]i), the CaR agonist spermine stimulated an increase in [Ca2+]i that was diminished in buffer without Ca2+ and was abolished after depletion of an intracellular Ca2+ pool with thapsigargin or after blocking IP3- and ryanodine receptor-mediated Ca2+ release with xestospongin C and with high concentration ryanodine, respectively. Spermine stimulated an increase in DAF-FM fluorescence in HAEC, consistent with NO production. Both the increase in [Ca2+]i and in NO production were reduced or absent in HAEC transfected with siRNA specifically targeted to the CaR. HAEC express a functional CaR that responds to the endogenous polyamine spermine with an increase in [Ca2+]i, primarily due to release of IP3- and ryanodine-sensitive intracellular Ca2+ stores, leading to the production of NO. Expression of alternatively spliced variants of the CaR may result in the absence of a functional response to other known CaR agonists in HAEC

  7. Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

    Science.gov (United States)

    Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

    2016-08-01

    Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. PMID:26969240

  8. 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

  9. 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 ...

  10. 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...

  11. [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

  12. CARDIOVASCULAR SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    6.1 Cardiac arrhythmias2004337 Expression and function changes of ryan-odine receptors and inostol 1,4,5-triphosphate receptors of atrial myocytes during atrial fibrillation GuoJihong (郭继鸿),et al. Dept Cardiol,People’s Hosp,

  13. 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...

  14. [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

  15. 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....

  16. 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.

  17. 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' ...

  18. 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 ...

  19. 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 & ...

  20. 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.

  1. 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, ...

  2. 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.

  3. 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.

  4. 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 ...

  5. 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

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    Science.gov (United States)

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  12. A Multicenter, Open-Label Study of an Intravenous Short-Acting β1-Adrenergic Receptor Antagonist Landiolol Hydrochloride for Coronary Computed Tomography Angiography by 16-Slice Multi-Detector Computed Tomography in Japanese Patients with Suspected Ischemic Cardiac Disease

    OpenAIRE

    Hirano, Masaharu; Yamashina, Akira; Hara, Kazuhiro; Ikari, Yuji; Jinzaki, Masahiro; Iino, Misako; Yamaguchi, Takuhiro; Tanimoto, Mitsunobu; Kuribayashi, Sachio; ,

    2014-01-01

    Background During coronary computed tomography (CT) angiography (CCTA), β-blockers (β-adrenergic receptor antagonists) have commonly been used to lower heart rate and improve image quality. Objectives The aim of this study was to investigate the image quality-improving effect as well as the heart rate-lowering effect of landiolol hydrochloride (an intravenous short-acting β1-adrenergic receptor antagonist) in CCTA by 16-slice multi-detector CT (MDCT). Methods A total of 39 subjects suspected ...

  13. 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)

  14. Receptor binding studies of the living heart

    International Nuclear Information System (INIS)

    Receptors form a class of intrinsic membrane proteins (or glycoproteins) defined by the high affinity and specificity with which they bind ligands. Many receptors are associated directly or indirectly with membrane ion channels that open or close after a conformational change of the receptor induced by the binding of the neurotransmitter. Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, and cardiomyopathy as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or postmortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue

  15. 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.

  16. A Positive GATA Element and a Negative Vitamin D Receptor-Like Element Control Atrial Chamber-Specific Expression of a Slow Myosin Heavy-Chain Gene during Cardiac Morphogenesis

    OpenAIRE

    Wang, Gang Feng; Nikovits, William; Schleinitz, Mark; Stockdale, Frank E.

    1998-01-01

    We have used the slow myosin heavy chain (MyHC) 3 gene to study the molecular mechanisms that control atrial chamber-specific gene expression. Initially, slow MyHC 3 is uniformly expressed throughout the tubular heart of the quail embryo. As cardiac development proceeds, an anterior-posterior gradient of slow MyHC 3 expression develops, culminating in atrial chamber-restricted expression of this gene following chamberization. Two cis elements within the slow MyHC 3 gene promoter, a GATA-bindi...

  17. 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.

  18. 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

  19. Rank-based genome-wide analysis reveals the association of Ryanodine receptor-2 gene variants with childhood asthma among human populations

    OpenAIRE

    Ding, Lili; Abebe, Tilahun; Beyene, Joseph; Wilke, Russell A; Goldberg, Arnon; Woo, Jessica G; Lisa J Martin; Rothenberg, Marc E.; Rao, Marepalli; Hershey, Gurjit K. Khurana; Chakraborty, Ranajit; Mersha, Tesfaye B

    2013-01-01

    Background The standard approach to determine unique or shared genetic factors across populations is to identify risk alleles in one population and investigate replication in others. However, since populations differ in DNA sequence information, allele frequencies, effect sizes, and linkage disequilibrium patterns, SNP association using a uniform stringent threshold on p values may not be reproducible across populations. Here, we developed rank-based methods to investigate shared or populatio...

  20. Methyl p-hydroxybenzoate (E-218) a preservative for drugs and food is an activator of the ryanodine receptor Ca2+ release channel

    OpenAIRE

    Cavagna, Dario; Zorzato, Francesco; Babini, Elena; Prestipino, Gianfranco; Treves, Susan

    2000-01-01

    Haloperidol is a drug used in the management of several psychotic disorders and its use has been linked to Neuroleptic Malignant Syndrome. In the present study we have investigated the effect of a commercial preparation of haloperidol, Serenase, on skeletal muscle sarcoplasmic reticulum.Addition of Serenase to isolated terminal cisternae caused a rapid release of calcium. We tested whether the active Ca2+-releasing substance was haloperidol or another compound present in the preparation.Our r...

  1. Cardiac Insulin Resistance and MicroRNA Modulators

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2012-01-01

    Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

  2. 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

  3. 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...

  4. 3D structure of muscle dihydropyridine receptor

    Directory of Open Access Journals (Sweden)

    Montserrat Samsó

    2015-01-01

    Full Text Available Excitation contraction coupling, the rapid and massive Ca2+ release under control of an action potential that triggers muscle contraction, takes places at specialized regions of the cell called triad junctions. There, a highly ordered supramolecular complex between the dihydropyridine receptor (DHPR and the ryanodine receptor (RyR1 mediates the quasi‐instantaneous conversion from T‐tubule depolarization into Ca2+ release from the sarcoplasmic reticulum (SR. The DHPR has several key modules required for EC coupling: the voltage sensors and II‐III loop in the alpha1s subunit, and the beta subunit. To gain insight into their molecular organization, this review examines the most updated 3D structure of the DHPR as obtained by transmission electron microscopy and image reconstruction. Although structure determination of a heteromeric membrane protein such as the DHPR is challenging, novel technical advances in protein expression and 3D labeling facilitated this task. The 3D structure of the DHPR complex consists of a main body with five irregular corners around its perimeter encompassing the transmembrane alpha 1s subunit besides the intracellular beta subunit, an extended extracellular alpha 2 subunit, and a bulky intracellular II‐III loop. The structural definition attained at 19 Å resolution enabled docking of the atomic coordinates of structural homologs of the alpha1s and beta subunits. These structural features, together with their relative location with respect to the RyR1, are discussed in the context of the functional data.

  5. 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

  6. 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

  7. 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)

  8. 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 ...

  9. 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

  10. [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

  11. 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

  12. 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...

  13. The current cardiac safety situation with antihistamines.

    Science.gov (United States)

    Yap, Y G; Camm, A J

    1999-03-01

    Antihistamines (H1-receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. The clinical interest of classical 'first generation' antihistamines is currently rather limited by their anticholinergic and sedative properties. The second generation of antihistamines, so-called non-sedating antihistamines, are free of these side-effects. However, since the 1990s, there have been reports that certain non-sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe dysrhythmias. These drugs prolong the monophasic action potential and surface electrocardiographic QT interval and may lead to the development of early after-depolarization and possibly torsades de pointes through an inhibition of potassium channel repolarization. Concomitant administration with drugs that inhibit the hepatic cytochrome P-450 (imidazole antifungals, macrolide antibiotics) or those that prolong the QT interval by the same or other mechanism (e.g. antiarrhythmics, antipsychotics, tricyclic antidepressants) increases their effect on the cardiac repolarization. The cardiac safety profile of newer non-sedating antihistamines requires confirmation. Drugs with low or no potential to block the K + rectification channel (e.g. IKr channels) are likely to possess cardiac safety advantages. Other drug-related factors such as the physico-chemical properties of the antihistamines and its metabolic profile may also contribute to the cardiac response. Mizolastine is a new non-sedating antihistamine with antiallergic properties. It has a good bioavailability and a metabolism via the cytochrome P-450 oxidation accounting for only 35% of its hepatic clearance. In addition, mizolastine displays low lipophilicity and consequently low cardiac tissue fixation. In clinical studies, mizolastine has not shown any dose-related increase in QT intervals. Its clinical use has not been associated with

  14. 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.)

  15. A case of catecholaminergic polymorphic ventricular tachycardia caused by two calsequestrin 2 mutations

    NARCIS (Netherlands)

    De La Fuente, Sam; Van Langen, Irene M.; Postma, Alex V.; Bikker, Henni; Meijer, Albert

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death. Two genes involved in calcium homeostasis, the ryanodine receptor gene and the calsequestrin 2 (CASQ2) gene, have been implicated in this disease. We describ

  16. Tsh receptor

    OpenAIRE

    Frauman, Albert

    2013-01-01

    The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage ...

  17. [3H]PN200-110 and [3H]ryanodine binding and reconstitution of ion channel activity with skeletal muscle membranes

    International Nuclear Information System (INIS)

    Skeletal muscle membranes derived either from the tubular (T) network or from the sarcoplasmic reticulum (SR) were characterized with respect to the binding of the dihydropyridine, [3H]PN200-110, and the alkaloid, [3H]ryanodine; polypeptide composition; and ion channel activity. Conditions for optimizing the binding of these radioligands are discussed. A bilayer pulsing technique is described and is used to examine the channels present in these membranes. Fusion of T-tubule membranes into bilayers revealed the presence of chloride channels and dihydropyridine-sensitive calcium channels with three distinct conductances. The dihydropyridine-sensitive channels were further characterized with respect to their voltage dependence. Pulsing experiments indicated that two different populations of dihydropyridine-sensitive channels existed. Fusion of heavy SR vesicles revealed three different ion channels; the putative calcium release channel, a potassium channel, and a chloride channel. Thus, this fractionation procedure provides T-tubules and SR membranes which, with radioligand binding and single channel recording techniques, provide a useful tool to study the characteristics of skeletal muscle ion channels and their possible role in excitation-contraction coupling

  18. 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.

  19. 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

  20. 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...

  1. 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)

  2. 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...

  3. 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 ...

  4. 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...

  5. Pioglitazone reverses down-regulation of cardiac PPARγ expression in Zucker diabetic fatty rats

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARγ in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARγ agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARγ, glucose transporter-4 and α-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARγ, glut-4, and α-MHC expression levels in diabetic ZDF rats. Cardiac [18F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARγ agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARγ expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin

  6. 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

  7. 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.

  8. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation.

    Directory of Open Access Journals (Sweden)

    Heidi Ehrentraut

    Full Text Available Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15 mg/g bodyweight or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced

  9. Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation

    Science.gov (United States)

    Boehm, Olaf; El Aissati, Sakina; Foltz, Fabian; Goelz, Lina; Goertz, David; Kebir, Sied; Weisheit, Christina; Wolf, Michael; Meyer, Rainer; Baumgarten, Georg

    2015-01-01

    Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR)-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4-/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15mg/g bodyweight) or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization) signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4-/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4-/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced hyperinflammatory

  10. Investigation of myocardial receptors by PET in heart diseases

    International Nuclear Information System (INIS)

    Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, cardiomyopathy, as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or post mortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue. With the advent of Positron Emission Tomography (PET) it is now possible to obtain noninvasively quantitative determination of regional biochemical processes in the heart. The feasibility of characterizing muscarinic acetylcholine receptors, beta-adrenergic receptors and α1-adrenergic receptors has been shown in animals and in man. The receptor PET technique begins to be applied to clinical investigation

  11. 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 ...

  12. 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...

  13. 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...

  14. 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....

  15. 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

  16. 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

  17. 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...

  18. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  19. Adaptive servoventilation improves cardiac function and respiratory stability

    OpenAIRE

    Oldenburg, Olaf; Bitter, Thomas; Lehmann, Roman; Korte, Stefan; Dimitriadis, Zisis; Faber, Lothar; Schmidt, Anke; Westerheide, Nina; Horstkotte, Dieter

    2010-01-01

    Cheyne–Stokes respiration (CSR) in patients with chronic heart failure (CHF) is of major prognostic impact and expresses respiratory instability. Other parameters are daytime pCO2, VE/VCO2-slope during exercise, exertional oscillatory ventilation (EOV), and increased sensitivity of central CO2 receptors. Adaptive servoventilation (ASV) was introduced to specifically treat CSR in CHF. Aim of this study was to investigate ASV effects on CSR, cardiac function, and respiratory stability. A total ...

  20. 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.)

  1. [Manifestations of polymorphism of β1-adrenoreceptors in patients with newly diagnosed cardiac rhythm disorders].

    Science.gov (United States)

    Afanas'ev, S A; Rebrova, T Iu; Batalov, R E; Muslimova, É F; Borisova, E V; Popov, S V

    2013-01-01

    Individual peculiarities of the receptor apparatus of cardiomyocytes may determine pathological features of heart activity and susceptibility to pharmaceuticals. The possible role of beta-adrenoreceptor polymorphism in the development of cardiac rhythm disturbances is assessed by PCR. Special attention is given to A145G polymorphism of the ADRB1 gene in 127 patients with primary cardiac rhythm disorders. It was shown that AJ45G polymorphism (Ser49Gly) at DNA sites encoding for the amino acid sequence of beta-1 adrenoreceptors can influence the development of sex-specific cardiac rhythm disorders. PMID:24437165

  2. 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...

  3. 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.

  4. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  5. 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)

  6. 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....

  7. 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.)

  8. 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.

  9. 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

  10. 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...

  11. 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

  12. 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)

  13. 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

  14. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  15. 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

  16. PET and SPET tracers for mapping the cardiac nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, 17176 Stockholm (Sweden)

    2002-03-01

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[{sup 18}F]fluorodopamine, (-)-6-[{sup 18}F]fluoronorepinephrine and (-)-[{sup 11}C]epinephrine, and radiolabelled catecholamine analogues, such as [{sup 123}I]meta-iodobenzylguanidine, [{sup 11}C]meta-hydroxyephedrine, [{sup 18}F]fluorometaraminol, [{sup 11}C]phenylephrine and meta-[{sup 76}Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[{sup 18}F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility

  17. PET and SPET tracers for mapping the cardiac nervous system

    International Nuclear Information System (INIS)

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[18F]fluorodopamine, (-)-6-[18F]fluoronorepinephrine and (-)-[11C]epinephrine, and radiolabelled catecholamine analogues, such as [123I]meta-iodobenzylguanidine, [11C]meta-hydroxyephedrine, [18F]fluorometaraminol, [11C]phenylephrine and meta-[76Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[18F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging. (orig.)

  18. 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...

  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 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 ...

  1. 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.

  2. Mice lacking functional TRPV1 are protected from pressure overload cardiac hypertrophy

    OpenAIRE

    Buckley, Cadie L; Stokes, Alexander J.

    2011-01-01

    TRPV1 (transient receptor potential cation channel, subfamily V, member 1) is best studied in peripheral sensory neurons as a pain receptor; however TRPV1 is expressed in numerous tissues and cell types including those of the cardiovascular system. TRPV1 expression is upregulated in the hypertrophic heart, and the channel is positioned to receive stimulatory signals in the hypertrophic heart. We hypothesized that TRPV1 has a role in regulating cardiac hypertrophy. Using transverse aortic cons...

  3. Adaptive changes of the cardiac opioid system due to volume induced heart failure

    OpenAIRE

    Dehe, Lukas

    2016-01-01

    Knowledge about changes in the cardiac opioid system in congestive heart failure (CHF) is scarce. As such, this project investigated the cellular localization of the opioid receptors δ (DOR) and κ (KOR) in left ventricular (LV) myocardium. Opioid receptor (OR) binding sites were detected by radioligand binding. In addition, DOR and KOR localization was determined by double immunofluorescence confocal analysis in the left ventricle of male Wistar rats. DOR and KOR were colocalized with L-type ...

  4. A 15-step synthesis of (+)-ryanodol.

    Science.gov (United States)

    Chuang, Kangway V; Xu, Chen; Reisman, Sarah E

    2016-08-26

    (+)-Ryanodine and (+)-ryanodol are complex diterpenoids that modulate intracellular calcium-ion release at ryanodine receptors, ion channels critical for skeletal and cardiac muscle excitation-contraction coupling and synaptic transmission. Chemical derivatization of these diterpenoids has demonstrated that certain peripheral structural modifications can alter binding affinity and selectivity among ryanodine receptor isoforms. Here, we report a short chemical synthesis of (+)-ryanodol that proceeds in only 15 steps from the commercially available terpene (S)-pulegone. The efficiency of the synthesis derives from the use of a Pauson-Khand reaction to rapidly build the carbon framework and a SeO2-mediated oxidation to install three oxygen atoms in a single step. This work highlights how strategic C-O bond constructions can streamline the synthesis of polyhydroxylated terpenes by minimizing protecting group and redox adjustments. PMID:27563092

  5. Prenatal programming: adverse cardiac programming by gestational testosterone excess.

    Science.gov (United States)

    Vyas, Arpita K; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30-90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells -c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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 ...

  15. 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...

  16. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam; Ahern, Christopher A

    2011-01-01

    Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan-Williams cl...

  17. Effects of C-type natriuretic peptide on rat cardiac contractility

    OpenAIRE

    Brusq, Jean-Marie; Mayoux, Eric; Guigui, Laurent; Kirilovsky, Jorge

    1999-01-01

    Natriuretic peptide receptors have been found in different heart preparations. However, the role of natriuretic peptides in the regulation of cardiac contractility remains largely elusive and was, therefore, studied here.The rate of relaxation of electrically stimulated, isolated rat papillary muscles was enhanced (114.4±1.4%, P

  18. 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

  19. 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.)

  20. 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.)

  1. 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...

  2. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  3. Kappa and delta opioid receptor signaling is augmented in the failing heart

    OpenAIRE

    Bolte, Craig; Newman, Gilbert; Schultz, Jo El J.

    2009-01-01

    The opioidergic system, an endogenous stress pathway, modulates cardiac function. Furthermore, opioid peptide and receptor expression is altered in a number of cardiac pathologies. However, whether the response of myocardial opioid receptor signaling is altered in heart failure progression is currently unknown. Elucidating possible alterations in and effects of opioidergic signaling in the failing myocardium is of critical importance as opioids are commonly used for pain management, including...

  4. Effects of mibefradil on intracellular Ca2+ release in cultured rat cardiac fibroblasts and human platelets.

    Science.gov (United States)

    Eberhard, M; Miyagawa, K; Hermsmeyer, K; Erne, P

    1995-12-01

    The Ca2+ antagonist mibefradil at supratherapeutic concentrations induced a sustained increase of cytosolic Ca2+ in cultured rat cardiac fibroblasts and human platelets which lack sensitivity to K+ depolarization and Ca2+ channel block by verapamil or other Ca2+ antagonists. At concentrations above 10 microM, mibefradil elevated substantially cytosolic [Ca2+] without affecting the peak level of agonist-induced Ca2+ transients. These Ca2+-mobilizing actions of 10 or 100 microM mibefradil stand in contrast to the Ca2+ antagonism and relaxation of vascular muscle at 1 microM concentrations. Since a substantial part of mibefradil-induced increase in cytosolic Ca2+ was independent of extracellular Ca2+, and in order to define better the mechanism of Ca2+ increase, we exposed permeabilized cultured rat cardiac fibroblasts and human platelets to mibefradil at concentrations sufficiently high to identify covert effects. In permeabilized fibroblasts or platelets mibefradil at concentrations above 10 microM activated dose-dependent Ca2+ release from intracellular Ca2+ stores. Verapamil had no effect at concentrations of up to 100 microM. Mibefradil-induced Ca2+ release was not affected by ryanodine, thapsigargin, removal of ATP or dithioerythreitol, indicating that neither Ca2+ - nor disulfide reagent-induced Ca2+ release were involved and that mibefradil did not release Ca2+ by inhibition of the Ca2+-ATPase pump of endoplasmic reticulum. The rate, but not the amplitude, of mibefradil-induced Ca2+ release is increased up to fourfold in the presence of pentosan polysulphate or heparin, two potent inhibitors of inositol 1,4,5-trisphosphate-induced Ca2+ release. Depletion of Ca2+ stores of permeabilized cells inositol 1,4,5-trisphosphate in the presence of thapsigargin completely blocked mibefradil-induced Ca2+ release, and depletion of Ca2+ stores by mibefradil prevented further Ca2+ release by inositol 1,4,5-trisphosphate. Mibefradil at supratherapeutic concentrations (> or

  5. Vasopressin responses to unloading arterial baroreceptors during cardiac nerve blockade in conscious dogs

    Science.gov (United States)

    O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

    1992-01-01

    We examined the relative contributions of afferent input from the heart and from arterial baroreceptors in the stimulation of arginine vasopressin (AVP) secretion in response to hypotension caused by thoracic inferior vena caval constriction (TIVCC). Afferent input from cardiac receptors was reversibly blocked by infusing 2% procaine into the pericardial space to anesthetize the cardiac nerves. Acute cardiac nerve blockade (CNB) alone caused a rise in mean arterial pressure (MAP) of 24 +/- 3 mmHg but no change in plasma AVP. If the rise in MAP was prevented by TIVCC, plasma AVP increased by 39 +/- 15 pg/ml, and if MAP was allowed to increase and then was forced back to control by TIVCC, plasma AVP increased by 34 +/- 15 pg/ml. Thus the rise in MAP during CNB stimulated arterial baroreceptors, which in turn compensated for the loss of inhibitory input from cardiac receptors on AVP secretion. These results indicate that the maximum secretory response resulting from complete unloading of cardiac receptors at a normal MAP results in a mean increase in plasma AVP of 39 pg/ml in this group of dogs. When MAP was reduced 25% below control levels (from 95 +/- 5 to 69 +/- 3 mmHg) by TIVCC during pericardial saline infusion, plasma AVP increased by 79 +/- 42 pg/ml. However, the same degree of hypotension during CNB (MAP was reduced from 120 +/- 5 to 71 +/- 3 mmHg) led to a greater (P less than 0.05) increase in plasma AVP of 130 +/- 33 pg/ml. Because completely unloading cardiac receptors can account for an increase of only 39 pg/ml on average in this group of dogs, the remainder of the increase in plasma AVP must be due to other sources of stimulation. We suggest that the principal stimulus to AVP secretion after acute CNB in these studies arises from unloading the arterial baroreceptors.

  6. 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...

  7. The other side of cardiac Ca2+ signaling: transcriptional control

    Directory of Open Access Journals (Sweden)

    Alejandro eDomínguez-Rodríquez

    2012-11-01

    Full Text Available Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling, but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling. ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII and phosphatase calcineurin, both of which are activated by the complex Ca2+/ /Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n or cytoplasmic ([Ca2+]c, and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs in [Ca2+]c, needed to activate calcineurin.

  8. Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart

    OpenAIRE

    Karschin, A; Ho, B Y; Labarca, C; Elroy-Stein, O; Moss, B; Davidson, N.; Lester, H A

    1991-01-01

    In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar pathway in hippocampal neurons. To develop a system in which receptor/G protein/K+ channel coupling can be experimentally manipulated, we have used a highly efficient recombinant vaccinia virus vector system to express human serotonin 1A receptors in primary cultures of rat atrial myocytes. The expre...

  9. Radiation Therapy, Cardiac Risk Factors, and Cardiac Toxicity in Early-Stage Breast Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer. Methods and Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women ≥65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account. Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs. Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years

  10. 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

  11. 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

  12. 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.

  13. Induces vasodilatation of rat mesenteric artery in vitro mainly by inhibiting receptor-mediated Ca(2+)-influx and Ca(2+)-release

    DEFF Research Database (Denmark)

    Cao, Yong-Xiao; Zheng, Jian-Pu; He, Jian-Yu;

    2005-01-01

    inhibited the contraction derived from NA and CaCI2 in Ca(2+)-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular Ca2+ influx through the receptor-operated calcium channels and intracellular Ca2+ release from the Ca2+ store. Atropine......-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the (alpha1-adrenoreceptor. The beta-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine...... had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular Ca2+ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from...

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    DEFF Research Database (Denmark)

    Brygger, Louise; Herrstedt, Jørn

    2014-01-01

    clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected...

  20. 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)

  1. 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.

  2. Functional cooperation of spns2 and fibronectin in cardiac and lower jaw development

    Directory of Open Access Journals (Sweden)

    Yu Hisano

    2013-06-01

    The lipid mediator sphingosine-1-phosphate (S1P is a regulator of cardiac development in zebrafish, as disruption of its receptor s1pr2 or transporter spns2 causes migration defects in cardiac progenitors. To examine the genetic interaction of S1P signaling and the cell adhesion molecule fibronectin, we have established a fn;spns2 double mutant. Cardiac migration defects in fn;spns2 mutants were more severe than those in fn or spns2 mutants. We further found that the lower jaw morphology was disorganized in the fn;spns2 mutant, while it had a slightly shortened anterior–posterior distance in the ventral pharyngeal arch in fn and spns2 mutants relative to wild type. Knockdown of fn in the s1pr2 mutant, but not in the s1pr1 mutant, resulted in severe defects in cardiac migration and ventral pharyngeal arch arrangement. Further, in the background of the fn mutant, knockdown of endothelin receptor A (ednra, which was downregulated in the spns2 mutant, caused pharyngeal defects resembling those in the fn;spns2 mutant. These results strongly suggest that Spns2-S1PR2 signaling and fibronectin cooperatively regulate both cardiac and lower jaw development in zebrafish.

  3. 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...

  4. 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 ...

  5. 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...

  6. 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 ...

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. [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

  12. 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…

  13. 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

  14. 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.)

  15. 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...

  16. 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.)

  17. 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

  18. Platelet-derived growth factor-D promotes fibrogenesis of cardiac fibroblasts

    OpenAIRE

    Zhao, Tieqiang; Zhao, Wenyuan; Chen, Yuanjian; Li, Victoria S.; Meng, Weixin; Sun, Yao

    2013-01-01

    Platelet-derived growth factor (PDGF)-D is a newly recognized member of the PDGF family with its role just now being understood. Our previous study shows that PDGF-D and its receptors (PDGFR-β) are significantly increased in the infarcted heart, where PDGFR-β is primarily expressed by fibroblasts, indicating the involvement of PDGF-D in the development of cardiac fibrosis. In continuing with these findings, the current study explored the molecular basis of PDGF-D on fibrogenesis. Rat cardiac ...

  19. 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.

  20. 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.

  1. The dominant negative thyroid hormone receptor beta-mutant delta337T alters PPAR-alpha signaling in heart

    Science.gov (United States)

    PPARalpha and TR independently regulate cardiac metabolism. Although ligands for both these receptors are currently under evaluation for treatment of congestive heart failure, their interactions or signaling cooperation have not been investigated in heart. We tested the hypothesis that cardiac TRs i...

  2. 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...

  3. 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

  4. 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.)

  5. 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

  6. 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

  7. 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.)

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Mineralocorticoid receptor blockade—a novel approach to fight hyperkalaemia in chronic kidney disease

    OpenAIRE

    Ritz, E.; Pitt, B

    2013-01-01

    Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K+ in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well.

  14. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways.

    Science.gov (United States)

    Huang, Tom H W; Yang, Qinglin; Harada, Masaki; Li, George Q; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-12-01

    The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling. PMID:16306813

  15. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.

    Science.gov (United States)

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R; Cozzi, Nicholas V; Jackson, Meyer B; Ruoho, Arnold E

    2009-02-13

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. PMID:19213917

  16. PGC-1α accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    International Nuclear Information System (INIS)

    Energy metabolism and Ca2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1α in cardiac Ca2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca2+ transients, suggesting that myofilament sensitivity to Ca2+ increased. Interestingly, the decay kinetics of global Ca2+ transients and Ca2+ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), but not Na+/Ca2+ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca2+ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca2+ homeostasis, because SR Ca2+ load and the propensity for Ca2+ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.

  17. 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

  18. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

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

  19. 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

  20. Calcium and IP3 dynamics in cardiac myocytes: Experimental and computational perspectives and approaches

    Directory of Open Access Journals (Sweden)

    Felix eHohendanner

    2014-03-01

    Full Text Available Calcium plays a crucial role in excitation-contraction coupling (ECC, but it is also a pivotal second messenger activating Ca2+-dependent transcription factors in a process termed excitation-transcription coupling (ETC. Evidence accumulated over the past decade indicates a pivotal role of inositol 1,4,5-trisphosphate receptor (IP3R-mediated Ca2+ release in the regulation of cytosolic and nuclear Ca2+ signals. IP3 is generated by stimulation of plasma membrane receptors that couple to phospholipase C (PLC, liberating IP3 from phosphatidylinositol 4,5-bisphosphate (PIP2. An intriguing aspect of IP3 signaling is the presence of the entire PIP2-PLC-IP3 signaling cascade as well as the presence of IP3Rs at the inner and outer membranes of the nuclear envelope (NE which functions as a Ca2+ store. The observation that the nucleus is surrounded by its own putative Ca2+ store raises the possibility that nuclear IP3-dependent Ca2+ release plays a critical role in ETC. This provides a potential mechanism of regulation that acts locally and autonomously from the global cytosolic Ca2+ signal underlying ECC. Moreover, there is evidence that: (i the sarcoplasmic reticulum (SR and NE are a single contiguous Ca2+ store; (ii the nuclear pore complex is the major gateway for Ca2+ and macromolecules to pass between the cytosol and the nucleoplasm; (iii the inner membrane of the NE hosts key Ca2+ handling proteins including the Na+/Ca2+ exchanger (NCX/GM1 complex, ryanodine receptors (RyRs, nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs, Na+/K+ ATPase and Na+/H+ exchanger. Thus, it appears that the nucleus represents a Ca2+ signaling domain equipped with its own ion channels and transporters that allow for complex local Ca2+ signals. Many experimental and modeling approaches have been used for the study of intracellular Ca2+ signaling but the key to understanding of the dual role of Ca2+ mediating ECC and ECT lays in quantitative differences of

  1. 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

  2. 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

  3. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  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. Ca2+-Clock-Dependent Pacemaking in the Sinus Node Is Impaired in Mice with a Cardiac Specific Reduction in SERCA2 Abundance

    Science.gov (United States)

    Logantha, Sunil Jit R. J.; Stokke, Mathis K.; Atkinson, Andrew J.; Kharche, Sanjay R.; Parveen, Sajida; Saeed, Yawer; Sjaastad, Ivar; Sejersted, Ole M.; Dobrzynski, Halina

    2016-01-01

    Background: The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) pump is an important component of the Ca2+-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. Methods and Results: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P clock with 2 μM ryanodine induced bradycardia that was less pronounced in Serca2 KO preparations (9 ± 1% vs. 20 ± 3% in Serca2 FF; P clock. Mathematical modeling was used to dissect the effects of membrane- and Ca2+-clock components on Serca2 KO mouse heart rate and sinus node action potential. Computer modeling predicted a slowing of heart rate with SERCA2 downregulation and the heart rate slowing was pronounced at >70% reduction in SERCA2 activity. Conclusions: Serca2 KO mice show a disrupted Ca2+-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function.

  6. Molecular determinants of angiotensin II type 1 receptor functional selectivity

    DEFF Research Database (Denmark)

    Aplin, Mark; Bonde, Marie Mi; Hansen, Jakob Lerche

    2008-01-01

    The angiotensin AT(1) receptor is an important pharmacological target in the treatment of cardiovascular disorders, such as hypertension, diabetic nephropathy, cardiac hypertrophy, arrhythmia and failure. Simultaneously, the AT(1) receptor has emerged to be a prominent model for the emerging...... concept that receptors may attain multiple active states with differentiated functional outcomes. Two major signalling pathways are employed by the AT(1) receptor, namely 1) the canonical G(q) protein-dependent activation of inositol phosphate turnover and intracellular calcium release, and 2) G protein......-independent recruitment of beta-arrestin-scaffolded signalling complexes that activate protein kinase pathways. Different states of receptor activation with preference for individual downstream pathways (functional selectivity) have been demonstrated in mutational studies of the AT(1) receptor and by pharmacological...

  7. 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

  8. 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...

  9. 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...

  10. 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

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Changes in cardiac performance and sympathetic stimulation during and after fractionated radiotherapy in a rat model

    International Nuclear Information System (INIS)

    The consequences of fractionated irradiation on the number of cardiac α- and β-adrenergic receptors, myocardial norepinephrine concentration and in vitro assessed heart function were studied in Sprague-Dawley rats. Animals were locally irradiated on the thorax with a total dose of 50 Gy, in 5 weeks, using two different fractionation schemes (5 x 2.0 Gy/week and 3 x 3.3 Gy/week). Functional and biochemical assays were performed during treatment and at 6 months after initiation of treatment. During fractionated irradiation, the numbers of α- and β-adrenergic receptors tended to rise. During this period, myocardial norepinephrine concentration remained fairly constant and no decrease in cardiac output was observed. At 6 months, a significant increase of the numbers of α- and β-adrenergic receptors was observed in the 3.3 Gy/fraction group compared to age-matched controls, p = 0.012 and p = 0.02, respectively. At this time point, the myocardial norepinephrine concentration had decreased below control levels (p = 0.008 for the 3.3. Gy/fraction schedule, and p = 0.03 for the 2.0 Gy/fraction schedule). At 6 months, the cardiac output declined to 61% (p = 0.009) and 69% (p = 0.04) of control values for the 3.3 and 2.0 Gy/fraction schedules, respectively. The present data clearly show development of late cardiac sequelae caused by fractionated thorax irradiation with a total dose of 50 Gy. Moreover, this study lends support to the importance of fraction size with regard to the severity of the radiation-induced cardiac damage

  19. A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Biagi Diogo G

    2012-01-01

    Full Text Available Abstract Background Calstabins 1 and 2 bind to Ryanodine receptors regulating muscle excitation-contraction coupling. Mutations in Ryanodine receptors affecting their interaction with calstabins lead to different cardiac pathologies. Animal studies suggest the involvement of calstabins with dilated cardiomyopathy. Results We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (FKBP12 and FKBP12.6. No missense variant was found. Five no-coding variations were found but not related to the disease. Conclusions These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.

  20. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    OpenAIRE

    Isales, Gregory M.; Hipszer, Rachel A.; Tara D Raftery; Chen, Albert; Stapleton, Heather M.; Volz, David C.

    2015-01-01

    Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-...

  1. Impact of AT2 receptor deficiency on postnatal cardiovascular development.

    Directory of Open Access Journals (Sweden)

    Daniel Biermann

    Full Text Available BACKGROUND: The angiotensin II receptor subtype 2 (AT2 receptor is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: Hearts from 1, 7, 14 and 56 days old wild-type (WT and AT2 receptor-deficient (KO mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of α-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca(2+ transient in response to isoprenaline when stimulated concomitantly with angiotensin II. CONCLUSION: The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.

  2. GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway.

    Science.gov (United States)

    Ishida, Hidekazu; Saba, Rie; Kokkinopoulos, Ioannis; Hashimoto, Masakazu; Yamaguchi, Osamu; Nowotschin, Sonja; Shiraishi, Manabu; Ruchaya, Prashant; Miller, Duncan; Harmer, Stephen; Poliandri, Ariel; Kogaki, Shigetoyo; Sakata, Yasushi; Dunkel, Leo; Tinker, Andrew; Hadjantonakis, Anna-Katerina; Sawa, Yoshiki; Sasaki, Hiroshi; Ozono, Keiichi; Suzuki, Ken; Yashiro, Kenta

    2016-07-26

    A surface marker that distinctly identifies cardiac progenitors (CPs) is essential for the robust isolation of these cells, circumventing the necessity of genetic modification. Here, we demonstrate that a Glycosylphosphatidylinositol-anchor containing neurotrophic factor receptor, Glial cell line-derived neurotrophic factor receptor alpha 2 (Gfra2), specifically marks CPs. GFRA2 expression facilitates the isolation of CPs by fluorescence activated cell sorting from differentiating mouse and human pluripotent stem cells. Gfra2 mutants reveal an important role for GFRA2 in cardiomyocyte differentiation and development both in vitro and in vivo. Mechanistically, the cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase and its established ligands. Collectively, our findings establish a platform for investigating the biology of CPs as a foundation for future development of CP transplantation for treating heart failure. PMID:27396331

  3. GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Hidekazu Ishida

    2016-07-01

    Full Text Available A surface marker that distinctly identifies cardiac progenitors (CPs is essential for the robust isolation of these cells, circumventing the necessity of genetic modification. Here, we demonstrate that a Glycosylphosphatidylinositol-anchor containing neurotrophic factor receptor, Glial cell line-derived neurotrophic factor receptor alpha 2 (Gfra2, specifically marks CPs. GFRA2 expression facilitates the isolation of CPs by fluorescence activated cell sorting from differentiating mouse and human pluripotent stem cells. Gfra2 mutants reveal an important role for GFRA2 in cardiomyocyte differentiation and development both in vitro and in vivo. Mechanistically, the cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase and its established ligands. Collectively, our findings establish a platform for investigating the biology of CPs as a foundation for future development of CP transplantation for treating heart failure.

  4. Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects

    Directory of Open Access Journals (Sweden)

    Spicer Douglas B

    2010-05-01

    Full Text Available Abstract Background Growth factors and their receptors are mediators of organogenesis and must be tightly regulated in a temporal and spatial manner for proper tissue morphogenesis. Intracellular regulators of growth factor signaling pathways provide an additional level of control. Members of the Sprouty family negatively regulate receptor tyrosine kinase pathways in several developmental contexts. To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural crest-derived tissues. Results Here we report that conditional expression of Spry1 in neural crest cells causes defects in craniofacial and cardiac development in mice. Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects. These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations. In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos. Conclusion Collectively, these data suggest that Spry1 is an important regulator of craniofacial and cardiac morphogenesis and perturbations in Spry1 levels may contribute to congenital disorders involving tissues of neural crest origin.

  5. Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

    Science.gov (United States)

    Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.

    1990-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

  6. 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.

  7. Pet measurements of postsynaptic muscarinic and beta adrenergic receptors in the heart

    International Nuclear Information System (INIS)

    There is ample evidence from both experimental and clinical studies that changes in β-adrenergic and muscarinic receptor density can be associated with such cardiac diseases as congestive heart failure, myocardial ischemia and infarction, cardiomyopathy, diabetes, or thyroid-induced muscle disease. Changes in B-adrenergic density also have been shown in the denervated transplanted heart. These alterations of cardiac receptors have been demonstrated in vitro on homogenates from samples collected mainly during surgery or post mortem. Recent developments of Positron Emission Tomography (PET) techniques and of radioligands suitable for cardiac receptor binding studies in vivo have made possible both the imaging and the measurement of receptor density. From these studies, important information is now available concerning physiologic and pathologic conditions, as well as alterations induced by treatment. For the investigation of myocardial B-adrenergic receptors we have used [11C] CGP 12177, a potent hydrophilic antagonist of the 3-adrenergic receptor. The quantification of myocardial muscarinic receptors in vivo has been obtained with [11C] MQNB, a nonmetabolized hydrophilic antagonist of the muscarinic receptor. Receptor density and affinity have been measured by a kinetic, nonequilibrium approach in an experimental protocol that provides sufficient data to determine values for all parameters from a single experiment

  8. 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 ...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. TRPV1 gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction

    OpenAIRE

    Huang, Wei; Rubinstein, Jack; Prieto, Alejandro R.; Thang, Loc Vinh; Wang, Donna H.

    2008-01-01

    The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by proton or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemia-reperfusion (I/R) injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes...

  17. Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

    OpenAIRE

    Gupta, Jayanta; Dominic, Elizabeth A.; Fink, Jeffrey C.; Ojo, Akinlolu O.; Barrows, Ian R.; Reilly, Muredach P.; Townsend, Raymond R.; Joffe, Marshall M.; Rosas, Sylvia E.; Wolman, Melanie; Patel, Samir S.; Keane, Martin G.; Feldman, Harold I.; Kusek, John W.; Raj, Dominic S.

    2015-01-01

    Background: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods: Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, hig...

  18. Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

    OpenAIRE

    Jayanta Gupta; Dominic, Elizabeth A.; Fink, Jeffrey C.; Ojo, Akinlolu O.; Barrows, Ian R.; Reilly, Muredach P.; Townsend, Raymond R.; Joffe, Marshall M.; Rosas, Sylvia E.; Melanie Wolman; Patel, Samir S.; Keane, Martin G.; Feldman, Harold I.; Kusek, John W.; Raj, Dominic S.

    2015-01-01

    Background Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-...

  19. Caveolin-3 inhibits growth signal in cardiac myoblasts in a Ca2+-dependent manner

    OpenAIRE

    Fujita, Takayuki; Otsu, Kouji; Oshikawa, Jin; Hori, Hideaki; Kitamura, Hitoshi; Ito, Takaaki; Umemura, Satoshi; Minamisawa, Susumu; Ishikawa, Yoshihiro

    2007-01-01

    Caveolin, a major protein component of caveolae, directly interacts with multiple signaling molecules, such as Ras and growth factor receptors, and inhibits their function. However, the role of the second messenger system in mediating this inhibition by caveolin remains poorly understood. We examined the role of Ca2+ -dependent signal in caveloin-mediated growth inhibition using a rat cardiac myoblast cell line (H9C2), in which the expression of caveolin-3, the muscle specific subtype, can be...

  20. HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy

    OpenAIRE

    Lee, Ting-I; Kao, Yu-Hsun; Tsai, Wen-Chin; Chung, Cheng-Chih; Chen, Yao-Chang; Chen, Yi-Jen

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) regulate cardiac glucose and lipid homeostasis. Histone deacetylase (HDAC) inhibitor has anti-inflammatory effects which may play a key role in modulating PPARs and fatty acid metabolism. The aim of this study was to investigate whether HDAC inhibitor, MPT0E014, can modulate myocardial PPARs, inflammation, and fatty acid metabolism in diabetes mellitus (DM) cardiomyopathy. Electrocardiography, echocardiography, and western blotting were used...

  1. Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy

    OpenAIRE

    Kirkpatrick Iain; Fang Tielan; Lytwyn Matthew; Fallah-Rad Nazanin; Jassal Davinder S

    2008-01-01

    Abstract Background Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10–15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy. Methods an...

  2. Nox2 and Nox4 influence neonatal c-kit+ cardiac precursor cell status and differentiation

    OpenAIRE

    Nadworny, Alyson S.; Guruju, Mallik R.; Poor, Daniel; Doran, Robert M.; Sharma, Ram V.; Kotlikoff, Michael I.; Davisson, Robin L.

    2013-01-01

    Redox status has emerged as critical in modulating stemness and lineage commitment in several precursor cell types. However, a role for redox genes, specifically NADPH oxidases (Nox), in cardiac precursor cells (CPCs) has not been established. We tested whether CPCs marked by type III receptor tyrosine kinase c-kit (c-kit+) exhibit a unique NADPH oxidase signature that confers precursor status and whether alterations in this profile are functionally linked to changes in lineage specification....

  3. Dicty_cDB: Contig-U13988-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available iac ryanodine receptor (R... 48 0.84 1 ( M59743 ) Rabbit cardiac muscle Ca-2+ release cha............................done Score E Sequences producing significant alignments: (bits) Value N ( AC116551 ) Dictyostelium disco...tatgatcaccaaaata 688 Score = 367 bits (185), Expect = e-101 Identities = 194/194 (100%) ...gtaa 1297 |||||||||||||| Sbjct: 1284 aaatacaccagtaa 1297 Score = 299 bits (151), Expect =...attataaaacc-aaatccagttgtaacaaatacaccagtaa 1325 Score = 36.2 bits (18), Expect = 0.092

  4. 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.

  5. 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

  6. Defects in cardiac function precede morphological abnormalities in fish embryos exposed to polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    Fish embryos exposed to complex mixtures of polycyclic aromatic hydrocarbons (PAHs) from petrogenic sources show a characteristic suite of abnormalities, including cardiac dysfunction, edema, spinal curvature, and reduction in the size of the jaw and other craniofacial structures. To elucidate the toxic mechanisms underlying these different defects, we exposed zebrafish (Danio rerio) embryos to seven non-alkylated PAHs, including five two- to four-ring compounds that are abundant in crude oil and two compounds less abundant in oil but informative for structure-activity relationships. We also analyzed two PAH mixtures that approximate the composition of crude oil at different stages of weathering. Exposure to the three-ring PAHs dibenzothiophene and phenanthrene alone was sufficient to induce the characteristic suite of defects, as was genetic ablation of cardiac function using a cardiac troponin T antisense morpholino oligonucleotide. The primary etiology of defects induced by dibenzothiophene or phenanthrene appears to be direct effects on cardiac conduction, which have secondary consequences for late stages of cardiac morphogenesis, kidney development, neural tube structure, and formation of the craniofacial skeleton. The relative toxicity of the different mixtures was directly proportional to the amount of phenanthrene, or the dibenzothiophene-phenanthrene total in the mixture. Pyrene, a four-ring PAH, induced a different syndrome of anemia, peripheral vascular defects, and neuronal cell death, similar to the effects previously described for potent aryl hydrocarbon receptor ligands. Therefore, different PAH compounds have distinct and specific effects on fish at early life history stages

  7. 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

  8. 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.

  9. 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

  10. 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.)

  11. [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

  12. 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)

  13. 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...

  14. [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

  15. 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

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. [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...

  2. 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...

  3. 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.)

  4. Glutamate receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P;

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  5. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette;

    2003-01-01

    In 1972, Brazeau et al. isolated somatostatin (somatotropin release-inhibiting factor, SRIF), a cyclic polypeptide with two biologically active isoforms (SRIF-14 and SRIF-28). This event prompted the successful quest for SRIF receptors. Then, nearly a quarter of a century later, it was announced...

  6. 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.

  7. 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.

  8. 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

  9. Extracellular ATP-induced nuclear Ca{sup 2+} transient is mediated by inositol 1,4,5-trisphosphate receptors in mouse pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zheng; Li, Zhengzheng; Peng, Gong; Chen, Xiaoli; Yin, Wenxuan [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Kotlikoff, Michael I. [Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States); Yuan, Zeng-qiang, E-mail: zqyuan@sun5.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Ji, Guangju, E-mail: gj28@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China)

    2009-05-01

    Extracellular ATP (eATP) induces an intracellular Ca{sup 2+} transient by activating phospholipase C (PLC)-associated P2X4 purinergic receptors, leading to production of inositol 1,4,5-trisphosphate (IP3) and subsequent Ca{sup 2+} release from intracellular stores in mouse pancreatic {beta}-cells. Using laser scanning confocal microscopy, Ca{sup 2+} indicator fluo-4 AM, and the cell permeable nuclear indicator Hoechst 33342, we examined the properties of eATP-induced Ca{sup 2+} release in pancreatic {beta}-cell nuclei. eATP induced a higher nuclear Ca{sup 2+} transient in pancreatic {beta}-cell nuclei than in the cytosol. After pretreatment with thapsigargin (TG), an inhibitor of sarco-endoplasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps, the amplitude of eATP-induced Ca{sup 2+} transients in the nucleus was still much higher than those in the cytosol. This effect of eATP was not altered by inhibition of either the plasma membrane Ca{sup 2+}-ATPase (PMCA) or the plasma membrane Na{sup +}/Ca{sup 2+} exchanger (NCX) by LaCl{sub 3} or by replacement of Na{sup +} with N-Methyl-Glucosamine. eATP-induced nuclear Ca{sup 2+} transients were abolished by a cell-permeable IP3R inhibitor, 2-aminoethoxydiphenyl borate (2-APB), but were not blocked by the ryanodine receptor (RyR) antagonist ryanodine. Immunofluorescence studies showed that IP3Rs are expressed on the nuclear envelope of pancreatic {beta}-cells. These results indicate that eATP triggers nuclear Ca{sup 2+} transients by mobilizing a nuclear Ca{sup 2+} store via nuclear IP3Rs.

  10. Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4

    DEFF Research Database (Denmark)

    Richter, Wito; Day, Peter; Agrawal, Rani; Bruss, Matthew D; Granier, Sébastien; Wang, Yvonne L; Rasmussen, Søren Gøgsig Faarup; Horner, Kathleen; Wang, Ping; Lei, Tao; Patterson, Andrew J; Kobilka, Brian; Conti, Marco

    2008-01-01

    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing...

  11. 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

  12. Rapid steroid hormone actions via membrane receptors.

    Science.gov (United States)

    Schwartz, Nofrat; Verma, Anjali; Bivens, Caroline B; Schwartz, Zvi; Boyan, Barbara D

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. PMID:27288742

  13. 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

  14. 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.

  15. 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 (...

  16. 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…

  17. 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

  18. 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...

  19. 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

  20. 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.