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Lois Choy, Jie Ming Yeo, Vivian Tse, Shing Po Chan, Gary Tse
The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony...
September 2016: IJC Heart & Vasculature
Gary Tse, Sheung Ting Wong, Vivian Tse, Yee Ting Lee, Hiu Yu Lin, Jie Ming Yeo
Pre-existing heterogeneities present in cardiac tissue are essential for maintaining the normal electrical and mechanical functions of the heart. Exacerbation of such heterogeneities or the emergence of dynamic factors can produce repolarization alternans, which are beat-to-beat alternations in the action potential time course. Traditionally, this was explained by restitution, but additional factors, such as cardiac memory, calcium handling dynamics, refractory period restitution, and mechano-electric feedback, are increasingly recognized as the underlying causes...
October 2016: Journal of Arrhythmia
Chris Amdisen, Anna K Keller, Rie Schultz Hansen, Rikke Nørregaard, Søren Palmelund Krag, Ulla Møldrup, Michael Pedersen, Bente Jespersen, Henrik Birn
INTRODUCTION: Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up...
2016: PloS One
Oruganti Sai Satish, K Sashikanth Srivastav
Till recently, ST segment elevation in the absence of conduction abnormalities or chest pain occurring particularly in young bradycardia individuals has been considered a normal variant called early repolarisation (ER). However, recent studies suggest a more worrisome picture as patients with history of idiopathic ventricular fibrillation showed increased prevalence of ER in ECG. ER is an ECG pattern characterised by elevation of the QRS-ST junction (J point) ≥ 2 mv from baseline in the inferior (II, III, aVF) or lateral (I, aVL, V4-V6) leads manifested as QRS slurring or notching...
July 2016: Journal of the Association of Physicians of India
Claudia Crocini, Cecilia Ferrantini, Raffaele Coppini, Marina Scardigli, Ping Yan, Leslie M Loew, Godfrey Smith, Elisabetta Cerbai, Corrado Poggesi, Francesco S Pavone, Leonardo Sacconi
Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2)...
October 17, 2016: Scientific Reports
Joshua Xu, Jessica G Y Luc, Kevin Phan
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5-2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF...
September 2016: Journal of Thoracic Disease
Julian Mustroph, Stefan Neef, Lars S Maier
Calcium/calmodulin-dependent protein kinase II (CaMKII) has emerged as key enzyme in many cardiac pathologies, especially heart failure (HF), myocardial infarction and cardiomyopathies, thus leading to contractile dysfunction and malignant arrhythmias. While many pathways leading to CaMKII activation have been elucidated in recent years, hardly any clinically viable compounds affecting CaMKII activity have progressed from basic in vitro science to in vivo studies. This review focuses on recent advances in anti-arrhythmic strategies involving CaMKII...
October 11, 2016: Pharmacology & Therapeutics
Li Wang, Xiaoqing Zhang, Cong Xu, Hui Liu, Jianhua Qin
Human induced pluripotent stem cells (hiPSCs) and appropriate scaffolds are of great interest in cardiac tissue engineering. In this work, we present a simple and new strategy to produce a thin collagen membrane with a natural microstructure from porcine tendons and reconstruct the functional cardiac tissues by recellularizing hiPSC-derived cardiomyocytes onto the membrane, for the first time. The collagen membrane maintained its intact properties after decellularization, the composition of which was identified as collagen I...
October 18, 2016: Biomaterials Science
Sheldon M Singh, Andre d'Avila, Young-Hoon Kim, Arash Aryana, J Michael Mangrum, Gregory F Michaud, Srinivas R Dukkipati, Conor D Barrett, E Kevin Heist, Michael K Parides, Kevin E Thorpe, Vivek Y Reddy
AIMS: Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group...
October 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Nicolas Clementy, Nazih Benhenda, Eric Piver, Bertrand Pierre, Anne Bernard, Laurent Fauchier, Jean-Christophe Pages, Dominique Babuty
Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months...
September 28, 2016: Scientific Reports
Anastasia Zagorianou, Meletios Marougkas, Stavros G Drakos, Nikolaos Diakos, Panagiotis Konstantopoulos, Despina N Perrea, Maria Anastasiou-Nana, Konstantinos Malliaras
Amiodarone is effective in suppressing arrhythmias in heart failure patients. We investigated the effect of long-term amiodarone administration on myocardial fibrosis and left ventricular (LV) remodeling in a porcine model of ischemic cardiomyopathy. Eighteen infarcted farm pigs were randomized to receive long-term amiodarone administration for 3 months (n = 9) or conventional follow-up (n = 9). Evolution of LV remodeling over 3 months post-myocardial infarction was examined at tissue level (myocyte size, myocardial fibrosis and vascular density assessed by whole-field digital histopathology), organ level (LV structure and function assessed by echocardiography), and systemic level (BNP and MMP-9 levels)...
2016: SpringerPlus
Jader Santos Cruz, Fabiana Simão Machado, Catherine Ropert, Danilo Roman-Campos
Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease...
August 11, 2016: Trends in Cardiovascular Medicine
Eleonora Grandi, Mary M Maleckar
Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies...
September 6, 2016: Pharmacology & Therapeutics
Siamak Salavatian, Eric Beaumont, Jean-Philippe Longpré, John Andrew Armour, Alain Vinet, Vincent Jacquemet, Kalyanam Shivkumar, Jeffrey Laurence Ardell
BACKGROUND: Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether pre-emptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. METHODS: IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n=8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs (2) stellate or vagal stimulation...
September 2, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Gary Tse, Bing Sun, Sheung Ting Wong, Vivian Tse, Jie Ming Yeo
The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K(+)] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca(2+)]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0...
September 2016: Biomedical Reports
J H Coote, R A Chauhan
Autonomic control of the heart has a significant influence over development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic activity is known to be upregulated during these conditions and hence the sympathetic nerves present a target for treatment. However, a better understanding of the anatomy and physiology of cardiac sympathetic nerves is required for the progression of clinical interventions. This review explores the organization of the cardiac sympathetic nerves, from the preganglionic origin to the postganglionic innervations, and provides an overview of literature surrounding anti-arrhythmic therapies including thoracic sympathectomy and dorsal spinal cord stimulation...
August 2016: Autonomic Neuroscience: Basic & Clinical
Mark D Huffman, Kunal N Karmali, Mark A Berendsen, Adin-Cristian Andrei, Jane Kruse, Patrick M McCarthy, S C Malaisrie
BACKGROUND: People with atrial fibrillation (AF) often undergo cardiac surgery for other underlying reasons and are frequently offered concomitant AF surgery to reduce the frequency of short- and long-term AF and improve short- and long-term outcomes. OBJECTIVES: To assess the effects of concomitant AF surgery among people with AF who are undergoing cardiac surgery on short-term and long-term (12 months or greater) health-related outcomes, health-related quality of life, and costs...
August 22, 2016: Cochrane Database of Systematic Reviews
Asya Makhro, Qinghai Tian, Lars Kaestner, Dmitry Kosenkov, Giuseppe Faggian, Max Gassmann, Colin Schwarzwald, Anna Bogdanova
This study focuses on characterization of the cardiac N-methyl D-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia and ischemia occurring within physiological plasma concentration range for glutamate and glycine...
August 10, 2016: Journal of Cardiovascular Pharmacology
O D Kucherenko, V V Brek, B A Shelest, Yu A Kovaleva
The authors discuss modern approaches to the treatment of atrial fibrillation with reference to diabetic patients. The studies carried out thus far showed the importance of differential anti-arrhythmic therapy taking account of the clinical form of ciliary arrhythmia. The possibility of surgical and preventive treatment (up-stream therapy) is demonstrated.
2016: Klinicheskaia Meditsina
Armando Lagrutta, Haoyu Zeng, John Imredy, Bharathi Balasubramanian, Spencer Dech, Edward Lis, Jixin Wang, Jin Zhai, Joseph DeGeorge, Frederick Sannajust
Several clinical cases of severe bradyarrhythmias have been reported upon co-administration of the Hepatitis-C NS5B Nucleotide Polymerase Inhibitor (HCV-NI) direct-acting antiviral agent, sofosbuvir (SOF), and the Class-III anti-arrhythmic amiodarone (AMIO). We model the cardiac drug-drug interaction (DDI) between AMIO and SOF, and between AMIO and a closely-related SOF analog, MNI-1 (Merck Nucleotide Inhibitor #1), in functional assays of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), to provide mechanistic insights into recently reported clinical cases...
October 1, 2016: Toxicology and Applied Pharmacology
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