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Yuchi Han, Paul R Forfia, Anjali Vaidya, Jeremy A Mazurek, Myung H Park, Gautam Ramani, Stephen Y Chan, Aaron B Waxman
Introduction: A major determining factor on outcomes in patients with pulmonary arterial hypertension (PAH) is right ventricular (RV) function. Ranolazine, which is currently approved for chronic stable angina, has been shown to improve RV function in an animal model and has been shown to be safe in small human studies with PAH. We aim to study the effect of ranolazine on RV function using cardiovascular magnetic resonance (CMR) in patients with pulmonary hypertension (non-group 2 patients) and monitor the effect of ranolazine on metabolism using metabolic profiling and changes of microRNA...
2018: Open Heart
Alessandro Capucci, Laura Cipolletta, Federico Guerra, Irene Giannini
The main aim of current research on the field of atrial fibrillation (AF) treatment is to find new antiarrhythmic drugs with less side effects. Areas covered: Dronedarone and vernakalant showed promising result in term of efficacy and safety in selected patients. Ranolazine and colchicine are obtaining a role as a potential antiarrhythmic drug. Ivabradine is used in experimental studies for the rate control of AF. Moreover, new compounds (vanoxerine, moxonidine, budiodarone) are still under investigation. Monoclonal antibodies or selective antagonist of potassium channel are under investigation for long term maintenance of sinus rhythm...
March 6, 2018: Expert Opinion on Emerging Drugs
Zhenghang Zhao, Raymond K Kudej, Hairuo Wen, Nadezhda Fefelova, Lin Yan, Dorothy E Vatner, Stephen F Vatner, Lai-Hua Xie
Hibernating animals show resistance to hypothermia-induced cardiac arrhythmias. However, it is not clear whether and how mammalian hibernators are resistant to ischemia-induced arrhythmias. The goal of this investigation was to determine the susceptibility of woodchucks ( Marmota monax) to arrhythmias and their mechanisms after coronary artery occlusion at the same room temperature in both winter, the time for hibernation, and summer, when they do not hibernate. By monitoring telemetric electrocardiograms, we found significantly higher arrhythmia scores, calculated as the severity of arrhythmias, with incidence of ventricular tachycardia, ventricular fibrillation, and thus sudden cardiac death (SCD) in woodchucks in summer than they had in winter...
February 28, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mena Abdelsayed, Manpreet Ruprai, Peter C Ruben
E1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). The charge reversal mutant enhances the late sodium current (INa ) passed by the cardiac voltage-gated sodium channel (NaV 1.5), delaying cardiac repolarization. Exercise-induced triggers, like elevated temperature and cytosolic calcium, exacerbate E1784K late INa . In this study, we tested the effects of Ranolazine, the late INa blocker, on voltage-dependent and kinetic properties of E1784K at elevated temperature and cytosolic calcium...
February 26, 2018: Scientific Reports
Gennaro Riccio, Salvatore Antonucci, Carmela Coppola, Chiara D'Avino, Giovanna Piscopo, Danilo Fiore, Carlo Maurea, Michele Russo, Domenica Rea, Claudio Arra, Gerolama Condorelli, Fabio Di Lisa, Carlo G Tocchetti, Claudia De Lorenzo, Nicola Maurea
The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab...
2018: Frontiers in Physiology
Mauro Borzi, Alfredo Intorcia, Marco A Perrone, Giulia Grilli, Domenico Sergi, Martina Borzi, Francesco Romeo
No abstract text is available yet for this article.
February 9, 2018: Journal of Cardiovascular Medicine
F Sahli Costabal, J Yao, E Kuhl
Drugs often have undesired side effects. In the heart, they can induce lethal arrhythmias such as torsades de pointes. The risk evaluation of a new compound is costly and can take a long time, which often hinders the development of new drugs. Here we establish a high resolution, multiscale computational model to quickly assess the cardiac toxicity of new and existing drugs. The input of the model is the drug-specific current block from single cell electrophysiology; the output is the spatio-temporal activation profile and the associated electrocardiogram...
February 9, 2018: International Journal for Numerical Methods in Biomedical Engineering
Ricky D Turgeon, Glen J Pearson, Michelle M Graham
Half of women and 1/3 of men with angina and ischemia on stress testing have ischemia with no obstructive coronary artery disease (INOCA). These patients have quality of life (QoL) impairment comparable with patients with obstructive coronary artery disease. Clinicians generally treat INOCA with traditional antianginal agents despite previous studies demonstrating variable response to these medications. We performed a systematic review to evaluate the efficacy and safety of available pharmacologic therapies for INOCA...
January 10, 2018: American Journal of Cardiology
Iacopo Olivotto, Paolo G Camici, Piera Angelica Merlini, Claudio Rapezzi, Monica Patten, Vicent Climent, Gianfranco Sinagra, Benedetta Tomberli, Francisco Marin, Philipp Ehlermann, Lars S Maier, Alessandra Fornaro, Claudius Jacobshagen, Antonello Ganau, Luciano Moretti, Antonio Hernandez Madrid, Raffaele Coppini, Giorgio Reggiardo, Corrado Poggesi, Francesco Fattirolli, Luiz Belardinelli, Gianfranco Gensini, Alessandro Mugelli
BACKGROUND: The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND RESULTS: In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months...
January 2018: Circulation. Heart Failure
Edmund Cheung So, Sheng-Nan Wu, Yi-Ching Lo, Kevin Su
Voltage-gated Na+ currents (INa), known to contain many components (e.g., transient, resurgent and persistent INa) with unique gating properties, are involved in the generation and propagation of action potentials in excitable cells. In this study, how tefluthrin (Tef), a synthetic pyrethoid, and telmisartan (TEL), blocker of angiotensin II receptors can perturb those components of INa was investigated. The presence of either Tef or TEL increased the values of the gating charges of INa involved in the activation (za) and inactivation (za)...
January 3, 2018: Toxicology Letters
Brian W Gilbert, Max Sherard, Lindsey Little, Joshua Branstetter, Amber Meister, Joel Huffman
The antianginal drug ranolazine, because of its unique mechanism of action, has been shown to have antihyperglycemic effects. Here, we review the reports on the antihyperglycemic and metabolic effects of ranolazine. MEDLINE was searched from 2000 to October 1, 2016 using the terms ranolazine, antihyperglycemic, diabetes, cardiology, and antianginal. Studies and reviews were included if they were in English and provided relevant data to inform practicing clinicians. Ranolazine has been shown to be effective as an antihyperglycemic while utilized as monotherapy or in combination with traditional diabetic regimens...
February 15, 2018: American Journal of Cardiology
Xiaofang Zeng, Yinyin Zhang, Jianhui Lin, Haikuo Zheng, Jie Peng, Wei Huang
BACKGROUND: Recent studies have discovered that the antiangina agent ranolazine exerts a glucometabolic effect. OBJECTIVE: This systematic review and meta-analysis aimed to further understand the efficacy and safety profile of ranolazine in patients with diabetes. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and EMBASE databases and in up to July 2017. Efficacy end points were defined as the change in hemoglobin A1C (A1C) and fasting serum glucose (FSG) levels...
December 1, 2017: Annals of Pharmacotherapy
Ming-Chi Lai, Te-Yu Hung, Kao-Min Lin, Pi-Shan Sung, Shyh-Jong Wu, Chih-Sheng Yang, Yi-Jen Wu, Jing-Jane Tsai, Sheng-Nan Wu, Chin-Wei Huang
How sodium metabisulfite (SMB; Na2 S2 O5 ), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment...
November 29, 2017: Neurotoxicity Research
Ki E Park, C Richard Conti
Angina persists for many patients despite modern medical therapy and/or revascularization, and this is referred to as refractory angina. All patients with refractory angina must be treated with aggressive risk factor modification plus optimized medical management. β-Blockers and nitrates are usually first-line agents; however most patients require multiple medications for refractory symptom control. Novel agents, such as ranolazine and ivabradine, as well as non-pharmacologic therapies, such as enhanced external counterpulsation and cardiac rehabilitation, may provide relief or reduction of angina...
October 20, 2017: Trends in Cardiovascular Medicine
Marina Brockway, Anthony A Fossa, Jay W Mason
US Food and Drug Administration (FDA) investigators recently demonstrated in a crossover study that early (J-Tpeak c) and late (Tpeak -Tend ) repolarization duration can differentiate selective potassium block with a high arrhythmia risk from multichannel block with lower risk in subjects receiving dofetilide, verapamil, quinidine, or ranolazine. The purpose of this study was to determine if the findings by the FDA using their published software algorithm could be corroborated using an alternative software algorithm for the same metrics and to determine if methodological differences resulted in clinically meaningful differences in interpretation...
November 11, 2017: Clinical Pharmacology and Therapeutics
Shandong Yu, Gang Li, Christopher L-H Huang, Ming Lei, Lin Wu
Late sodium current (INaL) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak INa. The endogenous INaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced INa,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure...
November 10, 2017: Pflügers Archiv: European Journal of Physiology
Mayur Patel, Brenen Swofford, Edward Distler
A 50-year-old man with a history of vasospastic angina diagnosed 3 months prior presented with recurrent episodes of substernal chest pain. His chest pain was characterised as 'squeezing', lasting 10 min and typically occurred on awakening. Medications included isosorbide, nitroglycerin and ranolazine; however, due to lack of insurance he was unable to obtain these medications. On admission, patient was given a full-dose aspirin and nitroglycerin, which acutely worsened his chest pain. ECG did not reveal ischaemic changes and initial troponin was negative...
October 27, 2017: BMJ Case Reports
Helena Carstensen, Line Kjær, Maria Mathilde Haugaard, Mette Flethøj, Eva Zander Hesselkilde, Jørgen K Kanters, Steen Pehrson, Rikke Buhl, Thomas Jespersen
BACKGROUND: Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or non-cardiac toxicity. Efficacy can be improved by combining two compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side-effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined...
October 25, 2017: Journal of Cardiovascular Pharmacology
Peter Ong, Udo Sechtem
Patients with microvascular angina are characterized by angina pectoris with proof of myocardial ischemia in the absence of any relevant epicardial stenosis and without myocardial disease (type 1 coronary microvascular dysfunction according to Crea and Camici). Structural and functional alterations of the coronary microvessels (diameter < 500 µm) are the reason for this phenomenon. Frequently such alterations are associated with cardiovascular risk factors. Patients with angina pectoris without epicardial stenoses represent for 10 - 50 % of all patients undergoing coronary angiography depending on the clinical presentation...
October 2017: Deutsche Medizinische Wochenschrift
Fatima Samad, Anushree Agarwal, Zainab Samad
Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m2 ), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases...
2017: International Journal of Women's Health
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