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drug induced ECG changes

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https://www.readbyqxmd.com/read/29779119/a-chemosensitizer-drug-disulfiram-prevents-doxorubicin-induced-cardiac-dysfunction-and-oxidative-stress-in-rats
#1
Varsha K Sonawane, Umesh B Mahajan, Sachin D Shinde, Subhajit Chatterjee, Sandip S Chaudhari, Harshada A Bhangale, Shreesh Ojha, Sameer N Goyal, Chanakya N Kundu, Chandragouda R Patil
In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Within 48 h of injection, DOX treatment significantly altered ECG, elevated the ST height, and increased the QT and QRS intervals. It reduced the cardiac levels of injury markers like creatine kinase isoenzyme-MB and lactate dehydrogenase...
May 10, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29748178/prognostic-significance-of-the-sodium-channel-blocker-test-in-patients-with-brugada-syndrome
#2
Akira Ueoka, Hiroshi Morita, Atsuyuki Watanabe, Yoshimasa Morimoto, Satoshi Kawada, Motomi Tachibana, Masakazu Miyamoto, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito
BACKGROUND: A drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non-type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB-induced ECG changes and ventricular tachyarrhythmias (VTAs). METHODS AND RESULTS: We administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non-type 1 ECG)...
May 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29709876/chronic-vagus-nerve-stimulation-reverses-heart-rhythm-complexity-in-patients-with-drug-resistant-epilepsy-an-assessment-with-multiscale-entropy-analysis
#3
Hongyun Liu, Zhao Yang, Fangang Meng, Lei Huang, Wei Qu, Hongwei Hao, Jianguo Zhang, Luming Li
OBJECTIVE: Vagus nerve stimulation (VNS) is an adjunctive treatment in drug-resistant epilepsy. The alterations in heart rate dynamics through VNS are not well understood. This study aimed to determine changes in heart rhythm complexity in association with VNS and to relate the findings to the outcome of VNS treatment in patients with drug-resistant epilepsy. METHODS: We prospectively analyzed 32 patients with drug-resistant epilepsy, who underwent VNS implantation, and 32 age- and sex-matched healthy control subjects...
April 26, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29704608/comparison-of-one-and-three-lead-ecg-to-measure-cardiac-intervals-and-differentiate-drug-induced-multi-channel-block
#4
Robert Brockway, Marina Brockway, Brian Brockway, Robert Hamlin
INTRODUCTION: FDA has established initiatives to characterize clinical and non-clinical biomarkers to enable more precise prediction of proarrhythmia risk based upon knowledge of drug effect on multiple cardiac ion channels (Colatsky et al., 2016). The FDA has recently demonstrated superiority of early ventricular repolarization interval (JTp) in differentiating pure hERG block from multi-channel block in human subjects. Preclinical studies often acquire a single lead ECG, whereas FDA measurements of JTp were derived ​from a spatial vectorcardiogram computed using multiple leads...
April 25, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29627347/trpa1-mediates-the-cardiac-effects-of-acrolein-through-parasympathetic-dominance-but-also-sympathetic-modulation-in-mice
#5
Nicole Kurhanewicz, Allen Ledbetter, Aimen Farraj, Mehdi Hazari
Numerous studies have demonstrated that short-term air pollution exposure causes cardiac autonomic imbalance as measured by heart rate variability (HRV). We previously showed that a single exposure to acrolein, a ubiquitous gaseous component of air pollution, not only causes autonomic imbalance, but also increases arrhythmia through transient receptor potential A1 (TRPA1) cation channels. Thus, the goal of this study was to characterize acrolein-induced autonomic changes in both normal and TRPA1-knockout mice (KO)...
April 5, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29574456/modeling-short-qt-syndrome-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#6
Ibrahim El-Battrawy, Huan Lan, Lukas Cyganek, Zhihan Zhao, Xin Li, Fanis Buljubasic, Siegfried Lang, Gökhan Yücel, Katherine Sattler, Wolfram-Hubertus Zimmermann, Jochen Utikal, Thomas Wieland, Ursula Ravens, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
BACKGROUND: Short QT syndrome (SQTS), a disorder associated with characteristic ECG QT-segment abbreviation, predisposes affected patients to sudden cardiac death. Despite some progress in assessing the organ-level pathophysiology and genetic changes of the disorder, the understanding of the human cellular phenotype and discovering of an optimal therapy has lagged because of a lack of appropriate human cellular models of the disorder. The objective of this study was to establish a cellular model of SQTS using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)...
March 24, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29546612/drug-physiology-interaction-and-its-influence-on-the-qt-prolongation-mechanistic-modeling-study
#7
Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
June 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29505899/the-evaluation-of-endpoint-variability-and-implications-for-study-statistical-power-and-sample-size-in-conscious-instrumented-dogs
#8
Alan Y Chiang, Brian D Guth, Michael K Pugsley, C Michael Foley, Jennifer M Doyle, Michael J Engwall, John E Koerner, Stanley T Parish, R Dustan Sarazan
INTRODUCTION: The sensitivity of a given test to detect a treatment-induced effect in a variable of interest is intrinsically related to the variability of that variable observed without treatment and the number of observations made in the study (i.e. number of animals). To evaluate test sensitivity to detect drug-induced changes in myocardial contractility using the variable LVdP/dtmax , a HESI-supported consortium designed and conducted studies in chronically instrumented, conscious dogs using telemetry...
March 2, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29496179/protective-effects-of-total-flavonoids-from-clinopodium-chinense-benth-o-ktze-on-myocardial-injury-in-vivo-and-in-vitro-via-regulation-of-akt-nrf2-ho-1-pathway
#9
Hai-Jing Zhang, Rong-Chang Chen, Gui-Bo Sun, Long-Po Yang, Yin-di Zhu, Xu-Dong Xu, Xiao-Bo Sun
BACKGROUND: Clinopodium chinense (Benth.) O. Ktze is a traditional Chinese herbal medicine, which comprises the plant's total flavonoids. TFCC plays an important role in the treatment of cardiovascular disease. PURPOSE: The aim of the study was to study the protective effects and possible mechanism of TFCC against isoproterenol (ISO)-mediated myocardial injury in vivo and anoxia/reoxygenation (A/R)-induced H9c2 cell injury in vitro. METHODS: Male Sprague-Dawley (SD) rats were intragastrically pretreated with TFCC for 15 days...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29462915/pilocarpine-induced-status-epilepticus-is-associated-with-p-glycoprotein-induction-in-cardiomyocytes-electrocardiographic-changes-and-sudden-death
#10
Jerónimo Auzmendi, Bruno Buchholz, Jimena Salguero, Carlos Cañellas, Jazmín Kelly, Paula Men, Marcela Zubillaga, Alicia Rossi, Amalia Merelli, Ricardo J Gelpi, Alberto J Ramos, Alberto Lazarowski
Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE...
February 16, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29387113/magnesium-sulfate-protects-the-heart-against-carbon-monoxide-induced-cardiotoxicity-in-rats
#11
Kaveh Tabrizian, Hamideh Khodayari, Ramin Rezaee, Hosseinali Jahantigh, Gholamreza Bagheri, Konstantinos Tsarouhas, Mahmoud Hashemzaei
Carbon monoxide (CO), a toxic gas produced via incomplete fossil fuel combustion, has several poisonous effects in the heart including induction of necrosis, apoptosis, and electrocardiogram (ECG) changes. Magnesium sulfate (MS) is a drug with cardioprotective effects especially when used after ischemia/reperfusion. In the current study, we aimed to evaluate MS cardioprotective effects following CO poisoning. Animals were exposed to CO 3000 ppm for 1 h and immediately after the exposure period and on the next 4 days (a total of 5 consecutive doses given on a daily basis), MS (75, 150 and 300 mg/kg) was injected intraperitoneally (i...
February 2018: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29311442/usefulness-of-simultaneous-and-sequential-monitoring-of-glucose-level-and-electrocardiogram-in-monkeys-treated-with-gatifloxacin-under-conscious-and-nonrestricted-conditions
#12
Yu Yoshimatsu, Tomomichi Ishizaka, Katsuyoshi Chiba, Kazuhiko Mori
Drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. To assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (GLU) levels, the effect of gatifloxacin (GFLX) which was frequently associated with GLU abnormality and QT/QTc prolongations in the clinic on blood GLU and electrocardiogram (ECG) parameters was investigated in cynomolgus monkeys (n=4) given GFLX orally in an ascending dose regimen (10, 30, 60 and 100 mg/kg)...
January 3, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29304479/microrna-140-5p-aggravates-doxorubicin-induced-cardiotoxicity-by-promoting-myocardial-oxidative-stress-via-targeting-nrf2-and-sirt2
#13
Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29234678/follow-up-measurement-of-corrected-qt-interval-in-adult-patients-before-and-after-lung-transplantation
#14
Dirk Bandorski, Reinhard Hoeltgen, Nicole Becker, Winfried Padberg, Harilaos Bogossian, Christoph Wiedenroth, Matthias Arlt, Christian Hamm, Werner Seeger, Hossein Ardeschir Ghofrani, Matthias Hecker, Henning Gall, Konstantin Mayer
Background: Prolongation of the corrected QT (QTc) interval is well known for many drugs, some of which are an integral part of the therapeutic regimen after lung transplantation (LTX). Therefore, we investigated the QTc interval after LTX in the present study. Patients and Methods: The medical records of patients after LTX were studied for demographic data, indication of LTX, medication, and baseline and follow-up ECGs. The QT interval was corrected for the patient's heart rate using the different formulae of Bazett, Fridericia, Hodges, and Framingham...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29178247/isavuconazole-shortens-the-qtc-interval
#15
Sibylle C Mellinghoff, Matteo Bassetti, Daniela Dörfel, Stefan Hagel, Nicola Lehners, Andrzej Plis, Enrico Schalk, Antonio Vena, Oliver A Cornely
Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as a class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in a dose-related manner. Here, we assessed the effects of isavuconazole on the length of QTc interval. The objective of the study was to describe changes in the QTc interval induced by isavuconazole treatment. A total of 26 adult patients from 7 hospitals were included...
April 2018: Mycoses
https://www.readbyqxmd.com/read/29127703/comparison-of-two-highly-automated-ecg-algorithms-for-detection-of-drug-induced-cardiac-ion-channel-block
#16
Marina Brockway, Anthony A Fossa, Jay W Mason
US Food and Drug Administration (FDA) investigators recently demonstrated in a crossover study that early (J-Tpeak c) and late (Tpeak -Tend ) repolarization duration can differentiate selective potassium block with a high arrhythmia risk from multichannel block with lower risk in subjects receiving dofetilide, verapamil, quinidine, or ranolazine. The purpose of this study was to determine if the findings by the FDA using their published software algorithm could be corroborated using an alternative software algorithm for the same metrics and to determine if methodological differences resulted in clinically meaningful differences in interpretation...
November 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29021091/an-evaluation-of-multiple-algorithms-for-the-measurement-of-the-heart-rate-corrected-jtpeak-interval
#17
Jean-Philippe Couderc, Shiyang Ma, Alex Page, Connor Besaw, Jean Xia, W Brian Chiu, Johan de Bie, Jose Vicente, Martino Vaglio, Fabio Badilini, Saeed Babaeizadeh, Cheng-Hao Simon Chien, Mathias Baumert
Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips)...
November 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28866768/providers-response-to-clinical-decision-support-for-qt-prolonging-drugs
#18
Sunita Sharma, J Martijn Bos, Robert F Tarrell, Gyorgy J Simon, Bruce W Morlan, Michael J Ackerman, Pedro J Caraballo
Commonly used drugs in hospital setting can cause QT prolongation and trigger life-threatening arrhythmias. We evaluate changes in prescribing behavior after the implementation of a clinical decision support system to prevent the use of QT prolonging medications in the hospital setting. We conducted a quasi-experimental study, before and after the implementation of a clinical decision support system integrated in the electronic medical record (QT-alert system). This system detects patients at risk of significant QT prolongation (QTc>500ms) and alerts providers ordering QT prolonging drugs...
September 2, 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/28800628/genome-wide-analysis-of-sotalol-induced-ikr-inhibition-during-ventricular-repolarization-generepol-study-lack-of-common-variants-with-large-effect-sizes
#19
Joe-Elie Salem, Marine Germain, Jean-Sébastien Hulot, Pascal Voiriot, Bruno Lebourgeois, Jean Waldura, David-Alexandre Tregouet, Beny Charbit, Christian Funck-Brentano
Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing...
2017: PloS One
https://www.readbyqxmd.com/read/28712169/analytic-study-in-patients-presenting-to-a-tertiary-care-hospital-regarding-the-artemether-lumefantrine-induced-qtc-interval-changes-in-ecg
#20
Aliena Badshah, Iqbal Haider, Shams Suleman
BACKGROUND: Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QTc interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QTc interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy...
January 2017: Journal of Ayub Medical College, Abbottabad: JAMC
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