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https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#1
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29677051/electrocardiographic-predictors-of-atrial-fibrillation-in-nonhypertensive-and-hypertensive-individuals
#2
Arttu O Lehtonen, Ville L Langén, Kimmo Porthan, Mika Kähönen, Markku S Nieminen, Antti M Jula, Teemu J Niiranen
OBJECTIVE: The aim of this study was to compare the predictive value of ECG abnormalities for atrial fibrillation in nonhypertensive versus hypertensive individuals. METHODS: We recorded ECG and measured conventional cardiovascular risk factors in a nationwide population-based sample of 5813 Finns. We divided the participants into nonhypertensive (n = 3148) and hypertensive (n = 2665) individuals and followed the participants for incident atrial fibrillation events...
April 19, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29672935/electrocardiographic-effects-of-hawthorn-crataegus-oxyacantha-in-healthy-volunteers-a-randomized-controlled-trial
#3
Stephanie E Trexler, Elaine Nguyen, Samantha M Gromek, Marcy J Balunas, William L Baker
The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated...
April 19, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29672845/drug-induced-proarrhythmia-and-torsade-de-pointes-a-primer-for-students-and-practitioners-of-medicine-and-pharmacy
#4
REVIEW
J Rick Turner, Ignacio Rodriguez, Emily Mantovani, Gary Gintant, Peter R Kowey, Ralph J Klotzbaugh, Krishna Prasad, Philip T Sager, Norman Stockbridge, Colette Strnadova
Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability...
April 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29671888/whole-exome-sequencing-reveals-microsatellites-dna-markers-for-response-to-dofetilide-initiation-in-patients-with-persistent-atrial-fibrillation-a-pilot-study
#5
Nick Kinney, Timothy R Larsen, David M Kim, Robin T Varghese, Steven Poelzing, Harold R Garner, Soufian T AlMahameed
BACKGROUND: Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associate with corrected QT (QTc) interval prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associate with congenital and acquired health conditions. OBJECTIVE: The purpose of this study was to explore potential genetic markers for QTc prolongation in response to DI in patients with persistent AF METHODS: We performed Whole Exome sequencing in a cohort of patients with persistent AF undergoing DI...
April 19, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29663449/mild-hypothermia-33%C3%A2-c-increases-the-inducibility-of-atrial-fibrillation-an-in-vivo-large-animal-model-study
#6
Martin Manninger, Alessio Alogna, David Zweiker, Birgit Zirngast, Stefan Reiter, Viktoria Herbst, Heinrich Maechler, Burkert M Pieske, Frank R Heinzel, Helmut Brussee, Heiner Post, Daniel Scherr
OBJECTIVE: Application of therapeutic mild hypothermia in patients after resuscitation, often accompanied by myocardial infarction, cardiogenic shock and systemic inflammation may impact on cardiac rhythm. We therefore tested susceptibility to atrial arrhythmias during hyperthermia (HT, 40.5°C), normothermia (NT, 38.0°C) and mild hypothermia (MH, 33.0°C). METHODS: Nine healthy, anesthetized closed-chest landrace pigs were instrumented with a quadripolar stimulation catheter in the high right atrium and a decapolar catheter in the coronary sinus...
April 16, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29660035/the-preventable-burden-of-work-related-ill-health
#7
P Cocco, R Agius
Background: The fraction of ill-health overall attributable to occupational conditions has not been extensively evaluated, thus contributing to the perception of a lesser relevance of education and research in occupational health in respect to other fields of medical research and practice. Aims: To assess the relevance of work-related conditions on the aetiology of human ill-health in different health domains. Methods: We extracted the risk estimates associated with heritability and with occupational risk factors for chronic lymphocytic leukaemia (CLL), major depressive disorder (MDD) and long QT syndrome (LQTS) from 13 published international reports...
April 12, 2018: Occupational Medicine
https://www.readbyqxmd.com/read/29659201/evaluation-of-eluxadoline-effect-on-cardiac-repolarization
#8
Laura Bonifacio, Thomas L Hunt, Gail McIntyre, Leonard S Dove, Paul S Covington
This study evaluated the effects of eluxadoline, a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, on cardiac repolarization. This evaluator-blinded, placebo- and positive-controlled, 4-period crossover study randomized healthy men and women to single oral doses of eluxadoline (therapeutic dose 100 mg or supratherapeutic dose 1000 mg), moxifloxacin 400 mg, or placebo. QT data were corrected using individual custom correction (QTcI). The primary endpoint was the change from baseline in QTcI intervals (ΔQTcI) between eluxadoline and placebo (ΔΔQTcI)...
April 16, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29657083/the-course-of-awake-breathing-disturbances-across-the-lifespan-in-rett-syndrome
#9
Daniel C Tarquinio, Wei Hou, Jeffrey L Neul, Gamze Kilic Berkmen, Jana Drummond, Elizabeth Aronoff, Jennifer Harris, Jane B Lane, Walter E Kaufmann, Kathleen J Motil, Daniel G Glaze, Steven A Skinner, Alan K Percy
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, is associated with a peculiar breathing disturbance exclusively during wakefulness that is distressing, and can even prompt emergency resuscitation. Through the RTT Natural History Study, we characterized cross sectional and longitudinal characteristics of awake breathing abnormalities in RTT and identified associated clinical features. Participants were recruited from 2006 to 2015, and cumulative lifetime prevalence of breathing dysfunction was determined using the Kaplan-Meier estimator...
April 12, 2018: Brain & Development
https://www.readbyqxmd.com/read/29652656/electrocardiogram-abnormalities-related-to-anti-malarials-in-systemic-lupus-erythematosus
#10
Taneisha K McGhie, Paula Harvey, Jiandong Su, Nicole Anderson, George Tomlinson, Zahi Touma
OBJECTIVES: Cardiotoxicity with potential conduction/structural abnormalities on electrocardiogram (ECG) have been reported with anti-malarial (AM). We aimed to study whether cumulative AM is associated with ECG abnormalities. METHODS: A standard resting supine ECG was performed on consecutive patients attending the Lupus Clinic since 2012. ECG abnormalities were grouped into structural [left ventricular hypertrophy or atrial enlargement] and conduction abnormalities [prolonged corrected QT interval (QTc), short PR interval, left bundle branch block (LBBB), right bundle branch block (RBBB) and atrioventricular block (AVB), bradycardia, tachycardia, premature atrial complex, ectopic atrial rhythm, atrial fibrillation, premature ventricular complex and ventricular bigeminy]...
April 13, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29651961/the-benefit-of-prescribing-vitamin-d-as-add-on-therapy-on-the-electrocardiographic-changes-in-epileptic-patients
#11
Marwan S M Al-Nimer
BACKGROUND: Epileptic children and adolescent have a significantly low serum level of vitamin D due to the effect of antiepileptic drugs on the vitamin D metabolism. Those patients are at risk of cardiovascular events. OBJECTIVE: This study aimed to show that epileptic patients who treated with antiepileptic drugs supplemented with vitamin D are free from the electrocardiograph changes compared with those treated with antiepileptic drugs. METHOD: This cross-sectional study included, 121 epileptic patients aged < 18 years of both genders with a history of idiopathic generalized tonic clonic seizure...
April 12, 2018: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/29651591/importance-of-qt-rr-hysteresis-correction-in-studies-of-drug-induced-qtc-interval-changes
#12
Marek Malik, Christine Garnett, Katerina Hnatkova, Lars Johannesen, Jose Vicente, Norman Stockbridge
QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological processes signifying how quickly and how much QT interval changes when heart rate changes, respectively. While QT interval duration is, as a rule, corrected for heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis is frequently omitted in studies of drug-induced QTc changes. This study used data from previously conducted thorough QT studies to investigate the extent of QTc errors caused by omitting the correction for QT/RR hysteresis, particularly in small clinical investigations...
April 12, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29650123/interplay-between-genetic-substrate-qtc-duration-and-arrhythmia-risk-in-patients-with-long-qt-syndrome
#13
Andrea Mazzanti, Riccardo Maragna, Gaetano Vacanti, Nicola Monteforte, Raffaella Bloise, Maira Marino, Lorenzo Braghieri, Patrick Gambelli, Mirella Memmi, Eleonora Pagan, Massimo Morini, Alberto Malovini, Martin Ortiz, Luciana Sacilotto, Riccardo Bellazzi, Lorenzo Monserrat, Carlo Napolitano, Vincenzo Bagnardi, Silvia G Priori
BACKGROUND: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). OBJECTIVES: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS...
April 17, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29648903/cardiotoxicity-of-anthracycline-ant-treatment-in-children-with-malignant-tumors
#14
Huimin Hu, Weiling Zhang, Dongsheng Huang, Qingmiao Yang, Jing Li, Yanan Gao
OBJECTIVE: To investigate the cardiotoxicity indexes in children with malignant tumors after the administration of anthracycline (ANT) chemotherapy. MATERIALS AND METHODS: Data from 131 children with malignant tumors who were treated using ANT chemotherapy at our hospital from January 2011 to December 2015 were collected to analyze the serologic indexes (such as N-terminal pro-brain natriuretic peptide [NT-proBNP] and isoenzyme of creatine kinase [CK-MB]) and changes in corrected QT interval(QT-c) and left ventricular ejection fraction (LVEF) before and after treatment with different ANT cumulative doses...
April 12, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29628379/quadriceps-tendon-autograft-for-primary-anterior-cruciate-ligament-reconstruction-a-systematic-review-of-comparative-studies-with-minimum-two-year-follow-up
#15
REVIEW
John W Belk, Matthew J Kraeutler, Hayden A Marshall, Jesse A Goodrich, Eric C McCarty
PURPOSE: To systematically review the literature in an effort to compare outcomes of patients undergoing primary anterior cruciate ligament reconstruction (ACLR) with a quadriceps tendon (QT) autograft versus a bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autograft. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to locate studies (Level of Evidence I-III) comparing the clinical outcomes of the QT autograft versus the BPTB or HT autograft in patients undergoing primary ACLR...
April 5, 2018: Arthroscopy: the Journal of Arthroscopic & related Surgery
https://www.readbyqxmd.com/read/29627227/effects-of-moxifloxacin-on-the-proarrhythmic-surrogate-markers-in-healthy-filipino-subjects-exposure-response-modeling-using-ecg-data-of-thorough-qt-qtc-study
#16
Suchitra Matsukura, Yuji Nakamura, Kiyotaka Hoshiai, Takashi Hayashi, Tadashi Koga, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Atsushi Sugiyama
Effects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeak c, Tpeak -Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, randomized, single-dose, placebo-controlled and two-period cross-over design in healthy Filipino subjects. QT interval was corrected by Fridericia's formula (QTcF). In the E14 time-based evaluation of ECG data, the largest ΔΔQTcF with 90% confidence interval was 14...
March 27, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29626474/canstatin-modulates-l-type-calcium-channel-activity-in-rat-ventricular-cardiomyocytes
#17
Keisuke Imoto, Masaki Hirakawa, Muneyoshi Okada, Hideyuki Yamawaki
Excessive increase of cytosolic Ca2+ through the activation of L-type Ca2+ channels (LTCCs) via β adrenergic receptor induces apoptosis of cardiomyocytes. Canstatin, a cleaved fragment of collagen type IV α2 chain, is abundantly expressed in normal heart tissue. We previously reported that canstatin inhibits β adrenergic receptor-stimulated apoptosis in cardiomyoblasts. Here, we tested the hyposeis that canstatin regulates LTCCs activity in ventricular cardiomyocytes. Collagen type IV α2 chain (COL4A2) small interfering (si) RNA (for canstatin suppression) or control siRNA was injected via jugular vein in Wistar rats...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29623481/effect-of-antazoline-on-electrophysiological-properties-of-atrial-muscle-and-conduction-system-of-the-heart
#18
Bartłomiej Jacek Bińkowski, Marcin Makowski, Paweł Kubiński, Andrzej Lubiński
PURPOSE: Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline...
April 6, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29622964/correlation-of-corrected-qt-dispersion-with-the-severity-of-coronary-artery-disease-detected-by-syntax-score-in-non-diabetic-patients-with-stemi
#19
Hatem Helmy, Ahmed Abdel-Galeel, Yehia Taha Kishk, Khaled Mohammed Sleem
Introduction: Determination of the QT interval dispersion by means of a standard ECG at rest has been widely used for cardiovascular risk assessment during the last 15 years as one of the recent explanations for the development of life threatening ventricular arrhythmias. However, little is known about the relation between QT dispersion and the severity of coronary artery atherosclerosis as defined by SYNTAX score. Aim of work: The present study was done to assess the correlation between QTc dispersion and the severity of coronary artery disease in acute ST elevation myocardial infarction (STEMI) detected by SYNTAX score...
June 2017: The Egyptian heart journal: (EHJ): official bulletin of the Egyptian Society of Cardiology
https://www.readbyqxmd.com/read/29622001/clinical-and-molecular-genetic-risk-determinants-in-adult-long-qt-syndrome-type-1-and-2-patients-koponen-et-al-follow-up-of-adult-lqts-patients
#20
Mikael Koponen, Aki S Havulinna, Annukka Marjamaa, Annukka M Tuiskula, Veikko Salomaa, Päivi J Laitinen-Forsblom, Kirsi Piippo, Lauri Toivonen, Kimmo Kontula, Matti Viitasalo, Heikki Swan
BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. METHODS: A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years...
April 5, 2018: BMC Medical Genetics
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