1,720,959 research outputs found
Reduced stretch-induced delayed force response and maintained Frank-Starling mechanism in failing human myocardium
No full textStretch-dependent modulation of [Na+](i), [Ca2+](i), and pH(i) in rabbit myocardium - a mechanism for the slow force response
No full textObjective: Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca2+ sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na+/H+ exchange (NHEI) and consecutive changes in pH(i) and/or [Na+](i) may underlie the SFR. Methods: Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca2+ indicator aequorin, the pH indicator BCECF, or the Na+ indicator SBFI and rapidly stretched from 88% (L-88) to 98% (L-98) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca2+](i), [Na+](i), or pH(i) were quantified before and after inhibition of NHE I by HOE 642 (3 mu M) or reverse-mode Na+/Ca2+ exchange (NCX) by KB-R 7943 (5 mu M). Results: In both Tyrode (n=21) and HEPES (n=22), developed force increased to similar to 160% during the 1st phase followed by a further increase to similar to 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n =4; normalized to the 1st phase) and a similar to 3 mM increase in [Na+](i) (n =4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pHi increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by similar to 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na+](i) by 72% and the delayed alkalinization. Conclusions: The data are consistent with the hypothesis that SFR results from increases in [Ca2+](i) secondary to altered flux via NCX in part resulting from increases in [Na+]i mediated by NHE1 (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved
Reduced stretch-induced delayed force response and maintained Frank-Starling mechanism in failing human myocardium
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
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
Variations 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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