1,720,976 research outputs found
Phosphorylation of the cardiac ryanodine receptor by Ca2+/calmodulin-dependent protein kinase II - The dominating twin of protein kinase A?
No full textMechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium
No full textBackground: Cardiac glycosides are characterized by a narrow therapeutic range with Ca2+ -overload and arrhythmias occurring at higher concentrations. Data on cardiac glycosides in isolated failing human myocardium are scarce and the frequency-dependent actions and toxicity of Strophanthidin have not yet been characterized. Aims: To determine inotropic responses and toxicity of Strophanthidin in failing human myocardium. Methods and results: Experiments were performed in trabeculae from 64 end-stage failing hearts. Developed force, and intracellular [Ca2+] and [Na+](i) were recorded with Strophanthidin (0.01 to 1 mu mol/L; 37 degrees C, 1 Hz) and compared to interventions with distinct mechanisms of action (elevated [Ca2+](o), Isoproterenol, and EMD57033). The effects of Strophanthidin on force-frequency behaviour were also assessed. Strophanthidin exerted concentration-dependent positive inotropic effects. These were paralleled by increases in intracellular [Na+] as well as increasing [Ca2+](i)-transients and SR-Ca2+-load. At high concentrations (>0.5 mu mol/L), Strophanthidin caused afterglimmers and aftercontractions, with declining developed force despite further increasing [Ca2+](i)-transients. The force-frequency-relationship and diastolic function at higher pacing rates was worsened by Strophanthidin in a concentration-dependent manner. Conclusions: Strophanthidin toxicity was dependent on concentration, calcium load, beating rate and beta-adrenergic receptor activation. Our data support the view that low doses, heart rate control and additional P-adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved
Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na(+)-Contraction Coupling
No full textBackground-Stretch elicits an immediate, followed by a delayed, inotropic response in various animal models and failing human myocardium. This study aimed to characterize functional differences in the stretch response between failing and nonfailing human myocardium. Methods and Results-Experiments were performed in muscle tissue from 86 failing and 16 nonfailing human hearts. Muscles were stretched from 88% to 98% of optimal length. Resulting immediate (Frank-Starling mechanism [FSM]) and delayed (slow-force response [SFR]) increases in twitch force were assessed before and after blockade of nitric oxide synthase, phosphatidylinositol-3-kinase, or reverse-mode Na+/Ca2+ exchange. Stretch-induced changes in [Na+](i) were measured using fluorescent indicator sodium-binding benzofuran isophthalate-AM. Nitric oxide synthase isoform expression was quantified by Western blot analysis. FSM was comparable between nonfailing (227 +/- 8%) and failing (222 +/- 9%) myocardium, whereas the additional increase during SFR (approximate to 5 minutes) was larger in nonfailing myocardium (to 126 +/- 3% versus 119 +/- 2% of force of FSM, respectively; P<0.05). Basal [Na+](i) and stretch-induced increase in [Na+](i) were lower in nonfailing myocardium. Inhibition of the Na+/H+ exchange largely reduced the increase in [Na+](i) and significantly blocked the SFR. In both groups, SFR was almost completely prevented by reverse-mode Na+/Ca+-exchanger inhibition. Although neuronal and inducible nitric oxide synthase expression were significantly upregulated in failing myocardium, inhibition of nitric oxide synthase and phosphatidylinositol-3-kinase had no effect on FSM or SFR. Conclusions-These data demonstrate a Na+-independent FSM and a Na+-dependent SFR in both nonfailing and failing human myocardium. The larger stretch-dependent increase in [Na+](i) in failing myocardium was associated with a blunted functional response, indicating impaired Na+-contraction coupling in the failing human heart. (Circ Heart Fail. 2009;2:47-55.)Deutsche Forschungsgemeinschaft [PI-414/1, PI-414/2, KFO 155
3-dependent Ca2+ release from perinuclear Ca2+ stores
No full textNuclear Ca2+ plays a key role in the regulation of gene expression. Inositol ( 1,4,5)-trisphosphate [Ins( 1,4,5) P-3)] might be an important regulator of nuclear Ca2+ but its contribution to nuclear Ca2+ signalling in adult cardiomyocytes remains elusive. We tested the hypothesis that endothelin-1 enhances nuclear Ca2+ concentration transients (CaTs) in rabbit atrial myocytes through Ins( 1,4,5) P-3-induced Ca2+ release from perinuclear stores. Cytoplasmic and nuclear CaTs were measured simultaneously in electrically stimulated atrial myocytes using confocal Ca2+ imaging. Nuclear CaTs were significantly slower than cytoplasmic CaTs, indicative of compartmentalisation of intracellular Ca2+ signalling. Endothelin-1 elicited a preferential ( 10 nM) or a selective (0.1 nM) increase in nuclear versus cytoplasmic CaTs. This effect was abolished by inhibition of endothelin-1 receptors, phospholipase C and Ins( 1,4,5) P-3 receptors. Fractional Ca2+ release from the sarcoplasmic reticulum and perinuclear stores was increased by endothelin-1 at an otherwise unaltered Ca2+ load. Comparable increases of cytoplasmic CaTs induced by beta-adrenoceptor stimulation or elevation of extracellular Ca2+ could not mimic the endothelin-1 effects on nuclear CaTs, suggesting that endothelin-1 specifically modulates nuclear Ca2+ signalling. Thus, endothelin-1 enhances nuclear CaTs in atrial myocytes by increasing fractional Ca2+ release from perinuclear stores. This effect is mediated by the coupling of endothelin receptor A to PLC-Ins( 1,4,5) P-3 signalling and might contribute to excitation-transcription coupling
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Pantoprazole induces a dose-dependent and reversible depression of contractile function in human myocardium
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Direct pro-arrhythmogenic effects of angiotensin II can be suppressed by AT1receptor blockade in human atrial myocardium
No full textAtrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Indirect evidence from clinical trials demonstrates that chronic inhibition of the renin-angiotensin-system (RAS) significantly reduces the incidence of AF. Since mechanisms of this protective effect of RAS-blockade are poorly understood, we directly tested proarrhythmic effects of angiotensin II (Ang II) in human atrial myocardium. Methods: Isolated trabeculae from human atrial appendages (n = 80) were electrically stimulated. We assessed isometric force and incidence of arrhythmic extra contractions (AECs) with and without increasing concentrations of Ang II (1-1000 nmol/L) in the absence or presence of receptor-blockade by saralasin (non-specific ATR-antagonist), irbesartan (AT1R-antagonist) or PD123319 (AT2R-antagonist). Results: Twitch force and AECs concentration-dependently increased with Ang II. Effects became significant at concentrations > 1 nmol/L Ang II and were maximal at 1000 nmol/L (increase in twitch force to 157 +/- 14% and AECs from 0 to 80%) saralasin and irbesartan partially prevented the inotropic effect of 100 nmol/L Ang II (by 45 +/- 12% and 68 +/- 6%; p < 0.05), and completely prevented the occurrence of AECs. Conclusion: Ang II exerts direct pro-arrhythmic effects in human atrial myocardium. These effects are mediated by AT I-receptors and can be prevented by AT1R-blockade. This mechanism may contribute to the beneficial effects of RAS-blockade on AF in clinical trials. (C) 2008 Published by Elsevier B.V. on behalf of European Society of Cardiology
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