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https://www.readbyqxmd.com/read/28105560/erratum-to-improvement-of-subjective-well-being-by-ranolazine-in-patients-with-chronic-angina-and-known-myocardial-ischemia-imwell-study
#1
Anthony A Bavry, Ki E Park, Calvin Y Choi, Ahmed N Mahmoud, Xuerong Wen, Islam Y Elgendy
No abstract text is available yet for this article.
January 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28101642/late-sodium-current-and-intracellular-ionic-homeostasis-in-acute-ischemia
#2
Carlotta Ronchi, Eleonora Torre, Riccardo Rizzetto, Joyce Bernardi, Marcella Rocchetti, Antonio Zaza
Blockade of the late Na(+) current (I NaL) protects from ischemia/reperfusion damage; nevertheless, information on changes in I NaL during acute ischemia and their effect on intracellular milieu is missing. I NaL, cytosolic Na(+) and Ca(2+) activities (Nacyt, Cacyt) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I NaL blockade. The results indicate that I NaL was enhanced during ISC in spite of changes in action potential (AP) contour; I NaL significantly contributed to Nacyt rise, but only marginally to Cacyt rise...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28044265/improvement-of-subjective-well-being-by-ranolazine-in-patients-with-chronic-angina-and-known-myocardial-ischemia-imwell-study
#3
Anthony A Bavry, Ki E Park, Calvin Y Choi, Ahmed N Mahmoud, Xuerong Wen, Islam Y Elgendy
INTRODUCTION: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. METHODS: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo...
January 2, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28024133/ranolazine-in-treatment-of-stable-angina-in-woman-with-atrial-fibrillation-and-intermittent-left-bundle-branch-block-a-case-report
#4
Natalia Yuriivna Osovska, Natalia Vitaliivna Kuzminova
Stable angina is the most frequent manifestation of ischemic heart disease (IHD) in women as compared to men (65% versus 37%). IHD in women has more favorable clinical course because myocardial infarction develops twice as rare as in men. Coronary angiography of angina patients demonstrates normal coronary arteries more frequently in women than in men. Microvascular angina (MVA) is found to be a rather common form of stable IHD as that particular diagnosis is made later in 20-30% of patients who previously underwent coronary angiography...
December 22, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28004395/myocardial-tissue-deformation-is-reduced-in-subjects-with-coronary-microvascular-dysfunction-but-not-rescued-by-treatment-with-ranolazine
#5
Michael D Nelson, Behzad Sharif, Jaime L Shaw, Galen Cook-Wiens, Janet Wei, Chrisandra Shufelt, Puja K Mehta, Louise E J Thomson, Daniel S Berman, Richard B Thompson, Eileen M Handberg, Carl J Pepine, Debiao Li, C Noel Bairey Merz
BACKGROUND: Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine-a late sodium current inhibitor-improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD). HYPOTHESIS: We hypothesized that ranolazine would beneficially alter diastolic function in CMD. METHODS: To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls...
December 22, 2016: Clinical Cardiology
https://www.readbyqxmd.com/read/27933435/ranolazine-promotes-muscle-differentiation-and-reduces-oxidative-stress-in-c2c12-skeletal-muscle-cells
#6
Terruzzi Ileana, Montesano Anna, Senesi Pamela, Vacante Fernanda, Benedini Stefano, Luzi Livio
PURPOSE: The purpose of this study is to investigate Ranolazine action on skeletal muscle differentiation and mitochondrial oxidative phenomena. Ranolazine, an antianginal drug, which acts blocking the late INaL current, was shown to lower hemoglobin A1c in patients with diabetes. In the present study, we hypothesized an action of Ranolazine on skeletal muscle cells regeneration and oxidative process, leading to a reduction of insulin resistance. METHODS: 10 μM Ranolazine was added to C2C12 murine myoblastic cells during proliferation, differentiation and newly formed myotubes...
December 8, 2016: Endocrine
https://www.readbyqxmd.com/read/27915058/larger-rate-dependence-of-late-sodium-current-in-cardiac-purkinje-cells-a-potential-link-to-arrhythmogenesis
#7
Wei Li, Ying Yu, Jian-Wen Hou, Zhi-Wen Zhou, Kai Guo, Peng-Pai Zhang, Zhi-Quan Wang, Jian-Hua Yan, Jian Sun, Qing Zhou, Yue-Peng Wang, Yi-Gang Li
BACKGROUND: Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (INaL) is rate dependent and contributes to rate dependence of repolarization. OBJECTIVE: This study sought to test our hypothesis that PCs have a larger rate dependence of INaL, contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs...
December 1, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27867290/ranolazine-is-an-effective-and-safe-treatment-of-adults-with-symptomatic-premature-ventricular-contractions-due-to-triggered-ectopy
#8
Gary L Murray
Early and delayed afterdepolarizations (EAD/DAD) cause triggered ventricular ectopy. Because ranolazine (RAN) suppresses EAD/DAD, we postulated that RAN might be effective in reducing premature ventricular contractions (PVCs). To assess the effect of RAN in patients with symptomatic PVCs due to triggered ectopy and its safety and tolerability. A total of 59 patients with symptomatic PVCs were identified from full-disclosure Holters. Doses of 500 and 1,000 mg offlabel RAN, daily, were given to 34 and 66% patients, respectively, and repeat Holters were performed prospectively during mean followup of 3...
December 2016: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/27829006/hyperthermia-influences-the-effects-of-sodium-channel-blocking-drugs-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Ibrahim El-Battrawy, Siegfried Lang, Zhihan Zhao, Ibrahim Akin, Gökhan Yücel, Sophie Meister, Bence Patocskai, Michael Behnes, Boris Rudic, Erol Tülümen, Volker Liebe, Malte Tiburcy, Jennifer Dworacek, Wolfram-Hubertus Zimmermann, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou
INTRODUCTION: Fever can increase the susceptibility to supraventricular and ventricular arrhythmias, in which sodium channel dysfunction has been implicated. Whether fever influences the efficacy of sodium channel blocking drugs is unknown. The current study was designed to investigate the temperature dependent effects of distinct sodium channel blocking drugs on the sodium currents in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS AND RESULTS: hiPSC-CMs were generated from human skin fibroblasts of a healthy donor...
2016: PloS One
https://www.readbyqxmd.com/read/27758968/the-novel-use-of-ranolazine-as-an-antiarrhythmic-agent-in-atrial-fibrillation
#10
REVIEW
C Michael White, Elaine Nguyen
OBJECTIVE: To review the limitations of current antiarrhythmic drugs in atrial fibrillation (AF) and discuss the rationale and clinical trials supporting the use of ranolazine in AF. DATA SOURCES: MEDLINE was searched from 1980 to September 2016 using the terms ranolazine, atrial fibrillation, coronary artery bypass grafting, and valve surgery STUDY SELECTION AND DATA EXTRACTION: English-language studies and reviews assessing antiarrhythmic drugs, including ranolazine, were incorporated...
October 6, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/27756767/ranolazine-reduces-atrial-fibrillatory-wave-frequency
#11
Eric W Black-Maier, Sean D Pokorney, Adam S Barnett, Peter Liu, Peter Shrader, Jason Ng, Jeffrey J Goldberger, Wojiech Zareba, James P Daubert, Augustus O Grant, Jonathan P Piccini
AIMS: Antiarrhythmic medications for the treatment of atrial fibrillation (AF) have limited efficacy and rare but potentially life-threatening side effects. Ranolazine is an antianginal agent that may have antiarrhythmic activity in AF. METHODS AND RESULTS: Using the Duke Enterprise Data Unified Content Explorer database, we analysed a cohort of AF patients on ranolazine. Patients served as their own historic control. Electrocardiograms (ECGs) were analysed before and after ranolazine initiation to determine the effect of ranolazine on dominant frequency (DF), f-wave amplitude, and organizational index (OI)...
October 17, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27746384/role-of-ranolazine-in-the-prevention-and-treatment-of-atrial-fibrillation-a-meta-analysis-of-randomized-clinical-trials
#12
Mengqi Gong, Zhiwei Zhang, Nikolaos Fragakis, Panagiotis Korantzopoulos, Konstantinos P Letsas, Guangping Li, Gan-Xin Yan, Tong Liu
BACKGROUND: Randomized controlled trials (RCTs) on the use of ranolazine (RN) for prevention and cardioversion of atrial fibrillation (AF) have yielded conflicting results. OBJECTIVE: The purpose of this study was to conduct a meta-analysis of RCTs to examine the potential role of RN in the prevention and cardioversion of AF. METHODS: PubMed and EMBASE were searched until June 2016. Of 484 initially identified studies, 8 RCTs were finally analyzed...
January 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27733495/ranolazine-for-congenital-long-qt-syndrome-type-iii-experimental-and-long-term-clinical-data
#13
Ehud Chorin, Dan Hu, Charles Antzelevitch, Aviram Hochstadt, Luiz Belardinelli, David Zeltser, Hector Barajas-Martinez, Uri Rozovski, Raphael Rosso, Arnon Adler, Jesaia Benhorin, Sami Viskin
BACKGROUND: The basic defect in long-QT syndrome type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential caused by mutations in the SCN5A gene. Most sodium channel blockers reduce the early (peak) and late components of the sodium current (INa and INaL), but ranolazine preferentially reduces INaL. We, therefore, evaluated the effects of ranolazine in LQT3 caused by the D1790G mutation in SCN5A. METHODS AND RESULTS: We performed an experimental study of ranolazine in TSA201 cells expressing the D1790G mutation...
October 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27713141/fibroblast-growth-factor-23-dysregulates-late-sodium-current-and-calcium-homeostasis-with-enhanced-arrhythmogenesis-in-pulmonary-vein-cardiomyocytes
#14
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Cheng-Chih Chung, Ting-I Lee, Wen-Chin Tsai, Shih-Ann Chen, Yi-Jen Chen
Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27690427/discovery-of-dihydrobenzoxazepinone-gs-6615-late-sodium-current-inhibitor-late-inai-a-phase-ii-agent-with-demonstrated-preclinical-anti-ischemic-and-antiarrhythmic-properties
#15
Jeff A Zablocki, Elfatih Elzein, Xiaofen Li, Dmitry O Koltun, Eric Q Parkhill, Tetsuya Kobayashi, Ruben Martinez, Britton Corkey, Haibo Jiang, Thao Perry, Rao Kalla, Gregory T Notte, Oliver Saunders, Michael Graupe, Yafan Lu, Chandru Venkataramani, Juan Guerrero, Jason Perry, Mark Osier, Robert Strickley, Gongxin Liu, Wei-Qun Wang, Lufei Hu, Xiao-Jun Li, Nesrine El-Bizri, Ryoko Hirakawa, Kris Kahlig, Cheng Xie, Cindy Hong Li, Arvinder K Dhalla, Sridharan Rajamani, Nevena Mollova, Daniel Soohoo, Eve-Irene Lepist, Bernard Murray, Gerry Rhodes, Luiz Belardinelli, Manoj C Desai
Late sodium current (late INa) is enhanced during ischemia by reactive oxygen species (ROS) modifying the Nav 1.5 channel, resulting in incomplete inactivation. Compound 4 (GS-6615, eleclazine) a novel, potent, and selective inhibitor of late INa, is currently in clinical development for treatment of long QT-3 syndrome (LQT-3), hypertrophic cardiomyopathy (HCM), and ventricular tachycardia-ventricular fibrillation (VT-VF). We will describe structure-activity relationship (SAR) leading to the discovery of 4 that is vastly improved from the first generation late INa inhibitor 1 (ranolazine)...
October 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27686005/emerging-drugs-for-the-treatment-of-angina-pectoris
#16
Cher-Rin Chong, Gao J Ong, John D Horowitz
Angina pectoris, or symptomatic myocardial ischaemia, reflects an impairment of coronary blood flow, and usually a deficiency of available myocardial energetics. Treatment options vary with the precise cause, which may vary with regards to the roles of increased myocardial oxygen demand versus reduced supply. Traditionally, organic nitrates, β-adrenoceptor antagonists, and non-dihydropyridine calcium antagonists were the only commonly used prophylactic anti-anginal agents. However, many patients failed to respond adequately to such therapy, and/or were unsuitable for their use...
December 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27665102/intracellular-calcium-oscillations-in-strongly-metastatic-human-breast-and-prostate-cancer-cells-control-by-voltage-gated-sodium-channel-activity
#17
Nahit Rizaner, Rustem Onkal, Scott P Fraser, Alessandro Pristerá, Kenji Okuse, Mustafa B A Djamgoz
The possible association of intracellular Ca(2+) with metastasis in human cancer cells is poorly understood. We have studied Ca(2+) signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca(2+) was measured using a membrane-permeant fluorescent Ca(2+)-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca(2+) oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively)...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27621502/ranolazine-induced-reversible-t-wave-inversions-with-prolonged-qtc-interval-progressive-multifocal-leukoencephalopathy-linked-to-fingolimod-losartan-induced-sprue-like-enteropathy-nivolumab-induced-psoriasiform-skin-eruption-hepatitis-b-reactivation-with-hepatitis
#18
EDITORIAL
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MED WATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MED WATCH, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested...
November 2015: Hospital Pharmacy
https://www.readbyqxmd.com/read/27621282/the-use-of-ratiometric-fluorescence-measurements-of-the-voltage-sensitive-dye-di-4-anepps-to-examine-action-potential-characteristics-and-drug-effects-on-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#19
M P Hortigon-Vinagre, V Zamora, F L Burton, J Green, G A Gintant, G L Smith
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and higher throughput platforms have emerged as potential tools to advance cardiac drug safety screening. This study evaluated the use of high bandwidth photometry applied to voltage-sensitive fluorescent dyes (VSDs) to assess drug-induced changes in action potential characteristics of spontaneously active hiPSC-CM. Human iPSC-CM from 2 commercial sources (Cor.4U and iCell Cardiomyocytes) were stained with the VSD di-4-ANEPPS and placed in a specialized photometry system that simultaneously monitors 2 wavebands of emitted fluorescence, allowing ratiometric measurement of membrane voltage...
December 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27580221/ranolazine-as-a-novel-therapy-for-pulmonary-arterial-hypertension
#20
Mengqi Gong, Nikolaos Fragakis, Chengzong Zhang, Zhiwei Zhang, Guangping Li, Tong Liu
No abstract text is available yet for this article.
November 15, 2016: International Journal of Cardiology
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