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https://www.readbyqxmd.com/read/28649790/safety-of-a-benazepril-and-pimobendan-combination-tablet-in-adult-healthy-dogs
#1
E A Kuntz, G Strehlau, J M Giraudel, J N King
The objective of the study was to investigate the safety of a combination tablet of benazepril and pimobendan, Fortekor PLUS(®) , in a randomized, blinded, parallel-group design study in healthy adult beagle dogs. The test article, Fortekor PLUS(®) tablets, was administered orally twice daily for 6 months at one, two, and four times the highest recommended dosage of 0.5 mg/kg benazepril hydrochloride/0.25 mg/kg pimobendan (four males and four females per group). An additional control group was sham-dosed...
June 26, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28646979/inhibition-of-rapid-delayed-rectifier-potassium-current-ikr-by-ischemia-reperfusion-and-its-recovery-by-vitamin-e-in-ventricular-myocytes
#2
Yaoxu Chen, Chunxia Yin, Yingying Yang, Zhuo Fan, Jinling Shang, Wen Tan
Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium (IKr) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of IKr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na2S2O4) in ventricular myocytes of guinea pigs...
July 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28645448/takotsubo-syndrome-presenting-as-syncope-in-a-patient-with-permanent-pacemaker
#3
Bharatraj Banavalikar, Sivasankaran Sivasubramonian, Narayanan Namboodiri, Krishna Kumar Mohanan Nair, Dibya Ranjan Behera, Ajitkumar Valaparambil
Takotsubo syndrome is an acute reversible heart failure syndrome triggered by physical or emotional stress, especially in postmenopausal women. Herein, we describe a case of a 31-year-old pacemaker dependent lady who presented with syncope after she was bereaved of her father. Electrocardiogram at admission revealed ventricular paced rhythm at 60/min, prolonged QT interval and frequent runs of torsades de pointes. Transthoracic echocardiogram and left ventriculogram revealed findings typical of Takotsubo syndrome...
May 18, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28643108/integrated-tk-td-modeling-for-drug-induced-concurrent-tachycardia-and-qt-changes-in-beagle-dogs
#4
Fan Wu, Tycho Heimbach, Panos Hatsis, Hai-Ming Tang, Raviprakash Dugyala, Qin Yue, Tao Wang, Handan He
Drug-induced cardiotoxicity, including tachycardia and QT prolongation, remains a major safety concern that needs to be identified and its risk mitigated in early stages of drug development. In the present study, an integrated toxicokinetic-toxicodynamic (TK-TD) modeling approach within a nonlinear mixed-effect modeling framework is applied to investigate concurrent abnormal heart rate and QT changes in three beagle dogs, using a Novartis internal compound (NVS001) as the case example. By accounting for saturable drug absorption, circadian rhythms, drug-effect tolerance, and nonlinear rate-dependency of QT interval, the dynamic TK-TD model captures the experimentally observed drug effects on heart rate and QT interval across a wide dosing range of NVS001 in beagle dogs...
June 22, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#5
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/28640933/could-ivabradine-be-a-new-treatment-for-the-short-qt-syndrome
#6
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/28638671/prenatal-diagnosis-of-atrioventricular-block-and-qt-interval-prolongation-by-fetal-magnetocardiography-in-a-fetus-with-trisomy-18-and-scn5a-r1193q-variant
#7
Lisheng Lin, Miho Takahashi-Igari, Yoshiaki Kato, Yoshihiro Nozaki, Mana Obata, Hiromi Hamada, Hitoshi Horigome
We report a case of fetal trisomy 18 with SCN5A R1193Q variant that presented with sinus bradycardia, 2 : 1 atrioventricular block (AVB), and QT interval prolongation. These complex arrhythmias were diagnosed by fetal magnetocardiography combined with ultrasound findings. Advanced AVB and ventricular arrhythmias were confirmed after birth. Genetic testing of the baby revealed a SCN5A R1193Q variant, which we considered could account for the various arrhythmias in this case.
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28638571/prevalence-of-qt-prolongation-and-associated-lvef-changes-in-diabetic-patients-over-a-four-year-retrospective-time-period
#8
Zhongju Lu, Lloyd Lense, Mohit Sharma, Ankit Shah, Ying Luu, Lucien Cardinal, Joan Faro, Alan Kaell
Aim: To evaluate the prevalence and longitudinal changes of prolonged QTc in DM patients admitted to our community hospital, and to determine, if any, its correlation with changes of left ventricular ejection fraction (LVEF). Methods: A retrospective chart review of patients with Type 1 (T1DM) and Type 2 (T2DM) with at least two admissions during a four-year period was performed to identify QTc interval, and LVEF, as measured on transthoracic echocardiogram. Changes in QTc and LVEF between patient hospital admissions were compared...
March 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28634649/assessment-of-cabozantinib-treatment-on-qt-interval-in-a-phase-3-study-in-medullary-thyroid-cancer-evaluation-of-indirect-qt-effects-mediated-through-treatment-induced-changes-in-serum-electrolytes
#9
Dale R Miles, Steven A Lacy, David R Wada, Steve Milwee, Yifah Yaron, Linh T Nguyen
PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration...
June 20, 2017: Cancer Chemotherapy and Pharmacology
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
#10
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/28627809/ivabradine-reduces-digitalis-induced-ventricular-arrhythmias
#11
Gerrit Frommeyer, Jan Weller, Christian Ellermann, Nils Bögeholz, Patrick Leitz, Dirk G Dechering, Simon Kochhäuser, Kristina Wasmer, Lars Eckardt
The I(f) channel inhibitor ivabradine is recommended for treatment of heart failure but also affects potassium currents and thereby prolongs ventricular repolarization. The aim of the present study was to examine the electrophysiological effects of ivabradine on digitalis-induced ventricular arrhythmias. Thirteen rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, the digitalis glycoside ouabain was infused (0.2μM). Monophasic action potentials and ECG showed a significant abbreviation of QT interval (-34ms,p<0...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28624975/deleterious-acute-and-chronic-effects-of-bradycardic-right-ventricular-apex-pacing-consequences-for-arrhythmic-outcome
#12
T R G Stams, A Dunnink, W M van Everdingen, H D M Beekman, R van der Nagel, B Kok, M F A Bierhuizen, M J Cramer, M Meine, M A Vos
In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28624887/voriconazole-induced-qt-prolongation-among-hemato-oncologic-patients-clinical-characteristics-and-risk-factors
#13
I Gueta, R Loebstein, N Markovits, Y Kamari, H Halkin, G Livni, H Yarden-Bilavsky
PURPOSE: The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. METHODS: We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. RESULTS: Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease...
June 17, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28624123/population-pharmacokinetic-pharmacodynamics-modeling-of-ibutilide-in-chinese-healthy-volunteers-and-patients-with-atrial-fibrillation-af-and-or-atrial-flutter-afl
#14
Zhijun Zeng, Li Wang, Lu Hua, Juanjuan Jiang, Huimin Pang, Yiling Huang, Yishi Li, Lei Tian
PURPOSE: The goal of this study was to develop a population pharmacokinetic (PK) and PK/pharmacodynamics (PD) model for ibutilide, to evaluate the time course of its effect on QT interval in Chinese. METHODS: The population PK and PK/PD model were developed using data from 40 Chinese healthy volunteers using nonlinear mixed-effects modeling, and the final population PK/PD model was applied on 100 patients with atrial fibrillation (AF) and/or atrial flutter (AFL)...
June 14, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28619993/low-extracellular-potassium-prolongs-repolarization-and-evokes-early-afterdepolarization-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#15
Jukka Kuusela, Kim Larsson, Disheet Shah, Chandra Prajapati, Katriina Aalto-Setälä
Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K(+) Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K(+) concentration ([K(+)]Ex) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28617967/holter-monitored-sudden-cardiac-arrest-after-atrioventricular-junction-ablation
#16
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/28613240/an-isoform-of-nedd4-2-plays-a-pivotal-role-in-electrophysiological-cardiac-abnormalities
#17
Shintaro Minegishi, Tomoaki Ishigami, Hisho Kawamura, Tabito Kino, Lin Chen, Rie Nakashima-Sasaki, Hiroshi Doi, Kengo Azushima, Hiromichi Wakui, Yumi Chiba, Kouichi Tamura
We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr)...
June 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28612305/the-cardiovascular-effect-of-single-injection-and-toxicologic-effects-of-repetitive-2-week-intravenous-administration-of-activin-a-bmp-2-chimera-in-beagle-dog
#18
Jae Hyup Lee, Senyon Choe, Shihuan Han
This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R-R interval, QT interval and QTcV interval on the electrocardiography. Also, when administered AB204 at the doses of 0...
June 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28612303/additive-proarrhythmic-effect-of-combined-treatment-with-qt-prolonging-agents
#19
Gerrit Frommeyer, Christina Fischer, Christian Ellermann, Dirk G Dechering, Simon Kochhäuser, Philipp S Lange, Kristina Wasmer, Michael Fehr, Lars Eckardt
Drug combinations may elevate the risk of proarrhythmia. The aim of the present study was to investigate whether combinations of non-cardiovascular agents induce an additive increase in the proarrhythmic risk. In 12 female rabbit hearts, a drug combination of cotrimoxazole (300 µM), ondansetron (5 µM) and domperidone (1 µM) was infused after obtaining baseline data. In another 13 hearts, a combination of cotrimoxazole (300 µM), ondansetron (5 µM) and erythromycin (300 µM) was infused. Monophasic action potentials and ECG displayed a significant QT prolongation in all groups...
June 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28612130/acute-brain-diseases-as-triggers-for-stress-cardiomyopathy-clinical-characteristics-and-outcomes
#20
Deena M Nasr, Sara Tomasini, Abhiram Prasad, Alejandro A Rabinstein
OBJECTIVE: To determine the clinical characteristics and outcomes of patients with neurogenic stress cardiomyopathy (NSC) among patients admitted to our neuroscience intensive care unit (NICU). METHODS: Following institutional review board approval, consecutive adult patients admitted to the NICU between 2009 and 2013 with definite and possible NSC were included. Data on patient demographics, baseline clinical information, cardiac function, and laboratory values were collected...
June 13, 2017: Neurocritical Care
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