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https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#1
Lena Rubi, Michael Kovar, Eva Zebedin-Brandl, Xaver Koenig, Manuel Dominguez-Rodriguez, Hannes Todt, Helmut Kubista, Stefan Boehm, Karlheinz Hilber
Retigabine, currently used as antiepileptic drug, has a wide range of potential medical uses. Administration of the drug in patients can lead to QT interval prolongation in the electrocardiogram and to cardiac arrhythmias in rare cases. This suggests that the drug may perturb the electrical properties of the heart, and the underlying mechanisms were investigated here. Effects of retigabine on currents through human cardiac ion channels, heterologously expressed in tsA-201 cells, were studied in whole-cell patch-clamp experiments...
June 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28637782/the-brugada-syndrome-susceptibility-gene-hey2-modulates-cardiac-transmural-ion-channel-patterning-and-electrical-heterogeneity
#2
Christiaan C Veerman, Svitlana Podliesna, Rafik Tadros, Elisabeth M Lodder, Isabella Mengarelli, Berend de Jonge, Leander Beekman, Julien Barc, Ronald Wilders, Arthur A Wilde, Bastiaan J Boukens, Ruben Coronel, Arie Verkerk, Carol Ann Remme, Connie R Bezzina
Rationale: Genome-wide association studies previously identified an association of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome (BrS). The causal gene and underlying mechanism remain unresolved. Objective: We used an integrative approach entailing transcriptomic studies in human hearts and electrophysiological studies in Hey2 heterozygous knockout mice (Hey2(+/-) ) to dissect the underpinnings of the 6q22.31 association with BrS. Methods and Results: We queried expression quantitative trait locus (eQTL) data acquired in 190 human left ventricular (LV) samples from the Genotype-Tissue Expression (GTEx) consortium for cis-eQTL effects of rs9388451 which revealed an association between BrS risk allele dosage and HEY2 expression (β=+0...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28633352/aortopulmonary-window-results-of-repair-beyond-infancy%C3%A2
#3
Sachin Talwar, Bharat Siddharth, Saurabh Kumar Gupta, Shiv Kumar Choudhary, Shyam Sunder Kothari, Rajnish Juneja, Anita Saxena, Balram Airan
OBJECTIVES: To study the anatomic and haemodynamic data and results of surgery in patients undergoing surgical repair of aortopulmonary window beyond infancy. METHODS: Between July 2005 and December 2015, 23 patients, older than 1 year undergoing surgery for aortopulmonary window were analysed retrospectively. Postoperative clinical and echocardiography follow-up were performed. RESULTS: Median age and weight at repair was 4 years (range 14 months-12 years) and 12 kg (range 3...
June 13, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28616649/earlier-pulmonary-valve-replacement-in-down-syndrome-patients-following-tetralogy-of-fallot-repair
#4
Rachel T Sullivan, Peter C Frommelt, Garick D Hill
The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis...
June 14, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28612155/the-role-of-spatial-organization-of-ca-2-release-sites-in-the-generation-of-arrhythmogenic-diastolic-ca-2-release-in-myocytes-from-failing-hearts
#5
Andriy E Belevych, Hsiang-Ting Ho, Ingrid M Bonilla, Radmila Terentyeva, Karsten E Schober, Dmitry Terentyev, Cynthia A Carnes, Sándor Györke
In heart failure (HF), dysregulated cardiac ryanodine receptors (RyR2) contribute to the generation of diastolic Ca(2+) waves (DCWs), thereby predisposing adrenergically stressed failing hearts to life-threatening arrhythmias. However, the specific cellular, subcellular, and molecular defects that account for cardiac arrhythmia in HF remain to be elucidated. Patch-clamp techniques and confocal Ca(2+) imaging were applied to study spatially defined Ca(2+) handling in ventricular myocytes isolated from normal (control) and failing canine hearts...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28606910/na-k-pump-inactivation-subsarcolemmal-na-measurements-and-cytoplasmic-ion-turnover-kinetics-contradict-restricted-na-spaces-in-murine-cardiac-myocytes
#6
Fang-Min Lu, Donald W Hilgemann
Decades ago, it was proposed that Na transport in cardiac myocytes is modulated by large changes in cytoplasmic Na concentration within restricted subsarcolemmal spaces. Here, we probe this hypothesis for Na/K pumps by generating constitutive transsarcolemmal Na flux with the Na channel opener veratridine in whole-cell patch-clamp recordings. Using 25 mM Na in the patch pipette, pump currents decay strongly during continuous activation by extracellular K (τ, ∼2 s). In contradiction to depletion hypotheses, the decay becomes stronger when pump currents are decreased by hyperpolarization...
June 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28606895/direct-adherence-measurement-using-an-ingestible-sensor-compared-with-self-reporting-in-high-risk-cardiovascular-disease-patients-who-knew-they-were-being-measured-a-prospective-intervention
#7
David Thompson, Teresa Mackay, Maria Matthews, Judith Edwards, Nicholas Peters, Susan B Connolly
BACKGROUND: Use of appropriate cardioprotective medication is a cornerstone of cardiovascular disease prevention, but less-than-optimal patient adherence is common. Thus, strategies for improving adherence are recommended to adopt a multifaceted approach. OBJECTIVE: The objective of our study was to test a system comprising a biodegradable, ingestible sensor for direct measurement of medication ingestion in a group of patients at elevated cardiovascular risk attending a cardiac prevention and rehabilitation program...
June 12, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28604360/chitosan-based-hydrogels-for-developing-a-small-diameter-vascular-graft-in-vitro-and-in-vivo-evaluation
#8
Audrey Aussel, Noélie Thébaud, Xavier Berard, Vincenzo Brizzi, Samantha Delmond, Reine Bareille, Robin Siadous, Chloe James, Jean Ripoche, Marlène Durand, Alexandra Montembault, Béatrice Burdin, Didier Letourneur, Nicolas L'Heureux, Laurent David, Laurence Bordenave
Vascular grafts made of synthetic polymers perform poorly in small-diameter applications (cardiac and peripheral bypass). Chitosan is a biocompatible natural polymer that can provide a novel biological scaffold for tissue engineering development. The goal of this study was to demonstrate the biocompatibility of a novel chitosan preparation in vitro and in vivo, and to assess its potential as a scaffold for vascular applications. Methods and Results. A series of experiments of increasing complexity, ranging from in vitro biocompatibility and hemocompatibility tests to in vivo studies in small and large animals (rat and sheep), was performed to provide a comprehensive analysis of chitosan hydrogels' biological properties...
June 12, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28592841/lipopolysaccharides-induced-inflammatory-responses-and-electrophysiological-dysfunctions-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Gökhan Yücel, Zhihan Zhao, Ibrahim El-Battrawy, Huan Lan, Siegfried Lang, Xin Li, Fanis Buljubasic, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Ursula Ravens, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592068/-reoperation-for-residual-aneurysm-of-coronary-anastomosis-after-bentall-procedure
#10
J R Xue, B Li, Y M Liu, T Bai, X D Pan, N N Liu, Z Qu, L Z Sun
Objective: To introduce a new operative method for residual aneurysm of coronary anastomosis after Bentall procedure. Methods: Between March 2011 and December 2012, six patients in Beijing Anzhen Hospital with residual aneurysm of coronary anastomosis (CT showed goldfish eye sign at the openings of coronary) after Bentall procedure underwent the operation of concentric circular patch procedure under cardiopulmonary bypass. Femoral artery, right atrium and upper right pulmonary artery cannulation were used for cardiopulmonary bypass, and the artificial vessel was transected after cardiac arrest...
May 30, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28573136/effects-of-wenxin-keli-on-cardiac-hypertrophy-and-arrhythmia-via-regulation-of-the-calcium-calmodulin-dependent-kinase-ii-signaling-pathway
#11
Xinyu Yang, Yu Chen, Yanda Li, Xiaomeng Ren, Yanwei Xing, Hongcai Shang
We investigated the effects of Wenxin Keli (WXKL) on the Calcium/Calmodulin dependent kinase II (CaMK II) signal transduction pathway with transverse aortic constriction (TAC) rats. Echocardiographic measurements were obtained 3 and 9 weeks after the surgery. Meanwhile, the action potentials (APDs) were recorded using the whole-cell patch clamp technique, and western blotting was used to assess components of the CaMK II signal transduction pathway. At both 3 and 9 weeks after treatment, the fractional shortening (FS%) increased in the WXKL group compared with the TAC group...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28570546/electrophysiological-analysis-of-human-pluripotent-stem-cell-derived-cardiomyocytes-hpsc-cms-using-multi-electrode-arrays-meas
#12
Luca Sala, Dorien Ward-van Oostwaard, Leon G J Tertoolen, Christine L Mummery, Milena Bellin
Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine...
May 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28560448/multiple-nav1-5-isoforms-are-functionally-expressed-in-the-brain-and-present-distinct-expression-patterns-compared-with-cardiac-nav1-5
#13
Jun Wang, Shao-Wu Ou, Yun-Fei Bai, Yun-Jie Wang, Zhi-Qing David Xu, Guo-Ming Luan
It has previously been demonstrated that there are various voltage gated sodium channel (Nav) 1.5 splice variants expressed in brain tissue. A total of nine Nav1.5 isoforms have been identified, however, the potential presence of further Nav1.5 variants expressed in brain neurons remains to be elucidated. The present study systematically investigated the expression of various Nav1.5 splice variants and their associated electrophysiological properties in the rat brain tissue, via biochemical analyses and whole‑cell patch clamp recording...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28552050/readthrough-of-scn5a-nonsense-mutations-r1623x-and-s1812x-question-gene-therapy-in-brugada-syndrome
#14
Siyong Teng, Jian Huang, Zhan Gao, Jie Hao, Yuejin Yang, Shu Zhang, Jielin Pu, Rutai Hui, Yongjian Wu, Zheng Fan
PURPOSE: Readthrough of nonsense mutation are used as gene-specific treatment in some genetic disease. Response to readthrough treatment is determined by readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to explore the harmful effect of nonsense mutation suppressions. METHODS: HEK293 cells were transfected with two SCN5A (encode cardiac Na+ channel) nonsense mutations, p.R1623X and p.S1812X. We applied two readthrough-enhancing methods (either aminoglycosides or by a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1)) to suppress these SCN5A nonsense mutations...
May 28, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28550095/small-conductance-calcium-activated-potassium-current-in-normal-rabbit-cardiac-purkinje-cells
#15
Thomas A Reher, Zhuo Wang, Chia-Hsiang Hsueh, Po-Cheng Chang, Zhenwei Pan, Mohineesh Kumar, Jheel Patel, Jian Tan, Changyu Shen, Zhenhui Chen, Michael C Fishbein, Michael Rubart, Penelope Boyden, Peng-Sheng Chen
BACKGROUND: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small-conductance calcium-activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin-sensitive SK currents are abundantly present in PCs. METHODS AND RESULTS: We studied 25 normal rabbit ventricles, including 13 patch-clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining...
May 26, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28549786/action-potential-based-mea-platform-for-in-vitro-screening-of-drug-induced-cardiotoxicity-using-human-ipscs-and-rat-neonatal-myocytes
#16
Danny Jans, Geert Callewaert, Olga Krylychkina, Luis Hoffman, Francesco Gullo, Dimiter Prodanov, Dries Braeken
Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution...
May 23, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28544840/redo-tricuspid-valve-repair-with-leaflet-augmentation-using-the-left-atrial-wall
#17
Daisuke Endo, Kenji Kuwaki, Taira Yamamoto, Atsushi Amano
The case is reported of a 79-year-old female who received a patch augmentation of the tricuspid anterior and septal leaflets with a resected left atrial wall to address recurrent tricuspid regurgitation, including tricuspid valve tethering. The patient was admitted to the authors' hospital for chronic heart failure with paravalvular leakage after aortic valve replacement and recurrent severe tricuspid regurgitation. She had undergone two previous cardiac surgeries. Re-tricuspid repair required an augmentation of the tricuspid valve leaflets in addition to tricuspid annuloplasty...
January 2017: Journal of Heart Valve Disease
https://www.readbyqxmd.com/read/28533740/correlation-of-ventricular-arrhythmogenesis-with-neuronal-remodeling-of-cardiac-postganglionic-parasympathetic-neurons-in-the-late-stage-of-heart-failure-after-myocardial-infarction
#18
Dongze Zhang, Huiyin Tu, Chaojun Wang, Liang Cao, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca(2+) currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28528050/novel-surgical-management-of%C3%A2-giant-aortic-arch-pseudoaneurysm
#19
Salah E Altarabsheh, Salil V Deo, Sakher M Alma'ayeh, Muhannad Jalookh, Ashraf O Alshabatat, Yagthan M Obeidat, Abeer Rababa'h, Fuad M Al-Azzam, Ashraf Fadel
Pseudoaneurysm of the aortic arch is a rare entity, usually seen after cardiac operations or chest trauma. Here we report a 32-year-old man who presented 10 years after blunt chest trauma with a giant aortic arch pseudoaneurysm. He finally underwent surgical intervention in which the pseudoaneurysm was closed from inside with use of an inlay patch method.
June 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28528049/an-old-solution-for-a-new-problem-eloesser-flap-management-of-infected-defibrillator-patches
#20
Heidi B Schubmehl, Huan Huan Sun, Jessica S Donington, Deane E Smith, Eugene A Grossi
Cardiac surgery patients with infected implantable cardioverter defibrillator hardware face high morbidity with both surgical and nonoperative management options. We present a case of infected epicardial patch defibrillator leads in a patient with prohibitively high risk of death with open surgical removal. As a less morbid alternative, an Eloesser flap was used to convert his presenting mediastinal empyema necessitans into a chronic, manageable wound.
June 2017: Annals of Thoracic Surgery
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