1,721,078 research outputs found
Ranolazine for rhythm control in atrial fibrillation: A systematic review and meta-analysis
No full textRanolazine for the Treatment of Heart Failure With Preserved Ejection Fraction: Background, Aims, and Design of the RALI-DHF Study
No full textBackground: Heart failure with preserved ejection fraction (HFpEF), formerly referred to as diastolic heart failure (DHF), accounts for >50% of all HF patients. So far, there has been no specific treatment for impaired left ventricular (LV) relaxation. Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current. Hypothesis: RAnoLazIne for the Treatment of Diastolic Heart Failure (RALI-DHF) is a prospective, single-center, randomized, double-blind, placebo-controlled proof-of-concept study to determine if ranolazine compared with placebo will be more effective in improving diastolic function in patients with HFpEF. Methods: Twenty patients with HFpEF (EF >= 50% and ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity [E/E']>15 or N-terminal pro-type brain natriuretic peptide >220 pg/mL) will be randomized to receive ranolazine or placebo in a 1.5:1 ratio during their catheterization if the LV end-diastolic pressure is >= 18 mm Hg and the time constant of relaxation (tau) is >= 50 ms. Treatment will consist of intravenous infusion of study drug (or placebo) for 24 hours, followed by oral treatment for a total of 14 days. Endpoints: The study will include the following exploratory endpoints: (1) change from baseline to 30 minutes from initiation of intravenous study drug administration during cardiac catheterization hemodynamic parameters at both resting and paced (120 beats per minute) conditions: t, LV end-diastolic pressure, and dP/dt(min).; and (2) change from baseline to day 14 in E/E', maximal oxygen consumption, and N-terminal pro-type brain natriuretic peptide. Conclusions: The RALI-DHF study is designed as a translational study to bridge the gap between basic science and therapeutics and to determine if ranolazine, compared with placebo, will be more effective in improving diastolic function in patients with HFpEF
Atrial fibrillation leads to electrical remodelling of Na currents. Role of INa inhibition by ranolazine on arrhythmias and contractility
No full textAtrial fibrillation leads to electrical remodelling of Na currents. Role of INa inhibition by ranolazine on arrhythmias and contractility
No full textCa/Calmodulin kinase II (CaMKII) overexpression increases effects of reactive oxygen species to enhance late I-Na and raise [Na+](i) and [Ca2+](i)
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EXPRESSION OF LYSYL OXIDASE-LIKE 2 (LOXL2) CORRELATES WITH LEFT ATRIAL SIZE AND FIBROTIC GENE EXPRESSION IN HUMAN ATRIAL FIBRILLATION
No full textBlocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction
No full textReactive oxygen species (ROS), including H2O2, cause intracellular calcium overload and ischemia-reperfusion damage. The objective of this study was to examine the hypothesis that H2O2-induced arrhythmic activity and contractile dysfunction are the results of an effect of H2O2 to increase the magnitude of the late sodium current (late I-Na). Guinea pig and rabbit isolated ventricular myocytes were exposed to 200 mu M H2O2. Transmembrane voltages and currents and twitch shortening were measured using the whole-cell patch-clamp technique and video edge detection, respectively. [Na+](i) and [Ca2+](i) were determined by fluorescence measurements. H2O2 caused a persistent late INa that was almost completely inhibited by 10 mu M tetrodotoxin (TTX). H2O2 prolonged the action potential duration (APD), slowed the relaxation rate of cell contraction, and induced early afterdepolarizations (EADs) and after contractions. H2O2 also caused increases of [Na+](i) and [Ca2+](i). Ranolazine (10 mu M), a novel inhibitor of late 1 Na, attenuated H2O2 induced late I-Na by 51 +/- 9%. TTX ( 2 mu M) or 10 mu M ranolazine attenuated H2O2-induced APD prolongation and suppressed EADs. Ranolazine accelerated the twitch relaxation rate in the presence of H2O2 and abolished H2O2-induced aftercontractions. Pretreatment of myocytes with ranolazine delayed and reduced the increases of APD, [Na+](i), and [Ca2+](i) caused by H2O2. In conclusion, the results confirm the hypothesis that an increase in late I-Na during exposure of ventricular myocytes to H2O2 contributes to electrical and contractile dysfunction and suggest that inhibition of late I-Na may offer protection against ROS-induced Na+ and Ca2+ overload
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
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