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https://www.readbyqxmd.com/read/28711067/pa-6-inhibits-inward-rectifier-currents-carried-by-v93i-and-d172n-gain-of-function-kir2-1-channels-but-increases-channel-protein-expression
#1
Yuan Ji, Marlieke G Veldhuis, Jantien Zandvoort, Fee L Romunde, Marien J C Houtman, Karen Duran, Gijs van Haaften, Eva-Maria Zangerl-Plessl, Hiroki Takanari, Anna Stary-Weinzinger, Marcel A G van der Heyden
BACKGROUND: The inward rectifier potassium current IK1 contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased IK1, short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC50 = 14 nM with inside-out patch clamp methodology) and specific IK1 inhibitor that interacts with the cytoplasmic pore region of the KIR2...
July 15, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28685701/the-role-of-quinidine-in-the-pharmacological-therapy-of-ventricular-arrhythmias-quinidine
#2
Milica Bajcetic, Teodora Vidonja Uzelac, Aleksandra Kezic, Milica Bajcetic
BACKGROUND: Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation...
July 7, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28660286/hydrocinnamic-acid-inhibits-the-currents-of-wt-and-sqt3-syndrome-related-mutants-of-kir2-1-channel
#3
Shuxi Ren, Chunli Pang, Yayue Huang, Chengfen Xing, Yong Zhan, Hailong An
Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.1. Here, we determined a monomer, hydrocinnamic acid (HA), as the effective component from 18 compounds of styrax. Our data show that HA can inhibit the currents of Kir2.1 channel in both excised inside-out and whole-cell patch with the IC50 of 5.21 ± 1.02 and 10.08 ± 0.46 mM, respectively...
June 28, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28659867/increased-short-term-beat-to-beat-qt-interval-variability-in-patients-with-impaired-glucose-tolerance
#4
Andrea Orosz, István Baczkó, Szabolcs Nyiraty, Anna E Körei, Zsuzsanna Putz, Róbert Takács, Attila Nemes, Tamás T Várkonyi, László Balogh, György Ábrahám, Péter Kempler, Julius Gy Papp, András Varró, Csaba Lengyel
Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 ± 11 years, body mass index (BMI): 31 ± 6 kg/m(2), fasting glucose: 6.0 ± 0.4 mmol/l, 120 min postload glucose: 9.0 ± 1.0 mmol/l, hemoglobin A1c (HbA1c): 5...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28640933/could-ivabradine-be-a-new-treatment-for-the-short-qt-syndrome
#5
EDITORIAL
Jules C Hancox
The short QT syndrome (SQTS) is a rare condition involving accelerated ventricular repolarization, abbreviated rate-corrected (QTc ) QT intervals on the electrocardiogram (ECG), poor rate adaptation of the QT interval, and an increased risk of atrial and ventricular arrhythmias and of sudden cardiac death (1-3). This article is protected by copyright. All rights reserved.
June 22, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28632743/in-silico-assessment-of-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-1-in-the-human-ventricles
#6
Cunjin Luo, Kuanquan Wang, Henggui Zhang
AIMS: Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1...
2017: PloS One
https://www.readbyqxmd.com/read/28617967/holter-monitored-sudden-cardiac-arrest-after-atrioventricular-junction-ablation
#7
Victor Waldmann, Eloi Marijon, Nicolas Combes
We present a case of sudden cardiac arrest seven hours after radiofrequency ablation of the atrioventricular junction for symptomatic permanent atrial fibrillation unresponsive to medical therapy. The Holter monitoring revealed a progressive increasing of QT interval after the procedure, highlighting the repolarization instability after acute changes in heart rates associated with modification of ventricular activation, leading to occurrence of short coupling interval ventricular extra beats and finally to a "Torsade de Pointes"...
June 15, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28611676/autonomic-modulation-in-patients-with-heart-failure-increases-beat-to-beat-variability-of-ventricular-action-potential-duration
#8
Bradley Porter, Martin J Bishop, Simon Claridge, Jonathan Behar, Benjamin J Sieniewicz, Jessica Webb, Justin Gould, Mark O'Neill, Christopher A Rinaldi, Reza Razavi, Jaswinder S Gill, Peter Taggart
Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined. Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation-recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28609477/atrial-arrhythmogenicity-of-kcnj2-mutations-in-short-qt-syndrome-insights-from-virtual-human-atria
#9
Dominic G Whittaker, Haibo Ni, Aziza El Harchi, Jules C Hancox, Henggui Zhang
Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28592292/effects-of-amiodarone-on-short-qt-syndrome-variant-3-in-human-ventricles-a-simulation-study
#10
Cunjin Luo, Kuanquan Wang, Henggui Zhang
BACKGROUND: Short QT syndrome (SQTS) is a newly identified clinical disorder associated with atrial and/or ventricular arrhythmias and increased risk of sudden cardiac death (SCD). The SQTS variant 3 is linked to D172N mutation to the KCNJ2 gene that causes a gain-of-function to the inward rectifier potassium channel current (I K1), which shortens the ventricular action potential duration (APD) and effective refractory period (ERP). Pro-arrhythmogenic effects of SQTS have been characterized, but less is known about the possible pharmacological treatment of SQTS...
June 7, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28584788/clinical-implications-of-new-drugs-and-regimens-for-the-treatment-of-drug-resistant-tuberculosis
#11
REVIEW
Yong-Soo Kwon
The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB...
May 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28574954/short-term-variability-of-repolarization-is-superior-to-other-repolarization-parameters-in-the-evaluation-of-diverse-antiarrhythmic-interventions-in-the-chronic-atrioventricular-block-dog
#12
Alexandre Bossu, Rosanne Varkevisser, Henriette D M Beekman, Marien J C Houtman, Marcel A G van der Heyden, Marc A Vos
Short-term variability (STV), to quantify beat-to-beat variability of repolarization, is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed but also in vulnerable patients with heart failure or drug-induced long QT syndrome. In the CAVB dog model, STV can specifically distinguish between safe and unsafe drugs in proarrhythmic screening. Conversely, this dog model also offers the possibility to evaluate antiarrhythmic strategies in a setting of Torsades de Pointes (TdP) induction with a standard IKr inhibitor...
June 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28569435/the-new-kids-on-the-block-of-arrhythmogenic-disorders-short-qt-syndrome-and-early-repolarization
#13
REVIEW
Andrea Mazzanti, Katherine Underwood, Dmitriy Nevelev, Shanna Kofman, Silvia G Priori
Short QT syndrome (SQTS) is one of the rarest inheritable cardiac channelopathies, characterized by an accelerated cardiac repolarization, which is also the substrate for the development of life-threatening ventricular arrhythmias. Up to this date, fewer than 200 SQTS cases have been reported in the literature worldwide. Patients with SQTS may experience a cardiac arrest as early as in the neonatal period or as late as 80 years old. The cumulative probability of experiencing a cardiac arrest by the fifth decade of life approaches 40%, highlighting the importance of early recognition and management...
June 1, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28566296/shortening-of-the-short-refractory-periods-in-short-qt-syndrome
#14
Anne Rollin, Estelle Gandjbakhch, Carla Giustetto, Chiara Scrocco, Carole Fourcade, Benjamin Monteil, Pierre Mondoly, Christelle Cardin, Carole Maupain, Fiorenzo Gaita, Philippe Maury
BACKGROUND: Diagnosis of short QT syndrome (SQTS) remains difficult in case of borderline QT values as often found in normal populations. Whether some shortening of refractory periods (RP) may help in differentiating SQTS from normal subjects is unknown. METHODS AND RESULTS: Atrial and right ventricular RP at the apex and right ventricular outflow tract as determined during standard electrophysiological study were compared between 16 SQTS patients (QTc 324±24 ms) and 15 controls with similar clinical characteristics (QTc 417±32 ms)...
May 31, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28556923/antiarrhythmic-properties-of-ivabradine-in-an-experimental-model-of-short-qt-syndrome
#15
Gerrit Frommeyer, Jan Weller, Christian Ellermann, Sven Kaese, Simon Kochhäuser, Philipp S Lange, Dirk G Dechering, Lars Eckardt
The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. 12 rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32ms,p<0...
May 29, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#16
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28510313/categorization-and-theoretical-comparison-of-quantitative-methods-for-assessing-qt-rr-hysteresis
#17
REVIEW
Hugo Gravel, Daniel Curnier, Nagib Dahdah, Vincent Jacquemet
BACKGROUND: In the human electrocardiogram, there is a lag of adaptation of the QT interval to heart rate changes, usually termed QT/RR hysteresis (QT-hys). Subject-specific quantifiers of QT-hys have been proposed as potential biomarkers, but there is no consensus on the choice of the quantifier. METHODS: A comprehensive literature search was conducted to identify original articles reporting quantifiers of repolarization hysteresis from the surface ECG in humans...
May 16, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28491751/structural-interplay-of-kv7-1-and-kcne1-is-essential-for-normal-repolarization-and-is-compromised-in-short-qt-syndrome-2-kv7-1-a287t
#18
Ina Rothenberg, Ilaria Piccini, Eva Wrobel, Birgit Stallmeyer, Jovanca Müller, Boris Greber, Nathalie Strutz-Seebohm, Eric Schulze-Bahr, Nicole Schmitt, Guiscard Seebohm
No abstract text is available yet for this article.
November 2016: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28490369/erratum-to-%C3%A2-novel-trigenic-cacna1c-des-mypn-mutations-in-a-family-of-hypertrophic-cardiomyopathy-with-early-repolarization-and-short-qt-syndrome
#19
Yanhong Chen, Hector Barajas-Martinez, Dongxiao Zhu, Xihui Wang, Chonghao Chen, Ruijuan Zhuang, Jingjing Shi, Xueming Wu, Yijia Tao, Weidong Jin, Xiaoyan Wang, Dan Hu
No abstract text is available yet for this article.
May 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28487061/the-spectrum-of-ambulatory-electrocardiographic-monitoring
#20
REVIEW
Harry G Mond
Since its introduction as a clinical investigative tool, the 12-lead electrocardiograph (ECG) has been the gold standard for recognition of cardiac arrhythmias. The resting 12-lead ECG, however, gives only a rhythm snapshot in time, whereas arrhythmias maybe short-lived, paroxysmal and even asymptomatic making documentation in many patients very difficult. To overcome this, ambulatory ECG monitoring has been developed as a means of recording the ECG in patients over a set period of time, whether it be short-, medium- or long-term...
April 13, 2017: Heart, Lung & Circulation
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