Progesterone Metabolites Inhibit the Human Ether‐a‐go‐go‐Related Gene and Predict QT Interval Length

2019 ◽  
Author(s):  
Tyler Shugg ◽  
Christian Egly ◽  
Chris W. Stamatkin ◽  
Avinash S. Patil ◽  
James E. Tisdale ◽  
...  
Keyword(s):  
Qt Interval ◽  
Interval Length ◽  
Related Gene ◽  
Progesterone Metabolites

The Effects of Sevoflurane and Propofol on QT Interval and Heterologously Expressed Human Ether-A-Go-Go Related Gene Currents in Xenopus Oocytes

2006 ◽  
Vol 102 (1) ◽  
pp. 98-103 ◽  
Author(s):  
Masana Yamada ◽  
Noboru Hatakeyama ◽  
Anna P. Malykhina ◽  
Mitsuaki Yamazaki ◽  
Yasunori Momose ◽  
...  
Keyword(s):  
Qt Interval ◽  
Xenopus Oocytes ◽  
Related Gene

scholarly journals Association of functional genetic variants of A-kinase anchoring protein 10 with QT interval length in full-term Polish newborns

2015 ◽  
Vol 1 ◽  
pp. 149-154 ◽  
Author(s):  
Beata Łoniewska ◽  
Mariusz Kaczmarczyk ◽  
Jeremy Simon Clark ◽  
Iwona Gorący ◽  
Anita Horodnicka-Józwa ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Qt Interval ◽  
Full Term ◽  
Interval Length ◽  
Anchoring Protein

scholarly journals QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

2014 ◽  
Vol 34 (5) ◽  
pp. 469-472 ◽  
Author(s):  
Maira S. Oliveira ◽  
Ruthnéa A.L. Muzzi ◽  
Leonardo A.L. Muzzi ◽  
Marcos Cherem ◽  
Matheus M. Mantovani
Keyword(s):  
Linear Regression ◽  
Qt Interval ◽  
Healthy Adult ◽  
Small Animal ◽  
Interval Length ◽  
Strongly Correlated ◽  
German Shepherd ◽  
Qt Intervals ◽  
Healthy Dogs ◽  
The Mean

The electrocardiography (ECG) QT interval is influenced by fluctuations in heart rate (HR) what may lead to misinterpretation of its length. Considering that alterations in QT interval length reflect abnormalities of the ventricular repolarisation which predispose to occurrence of arrhythmias, this variable must be properly evaluated. The aim of this work is to determine which method of correcting the QT interval is the most appropriate for dogs regarding different ranges of normal HR (different breeds). Healthy adult dogs (n=130; German Shepherd, Boxer, Pit Bull Terrier, and Poodle) were submitted to ECG examination and QT intervals were determined in triplicates from the bipolar limb II lead and corrected for the effects of HR through the application of three published formulae involving quadratic, cubic or linear regression. The mean corrected QT values (QTc) obtained using the diverse formulae were significantly different (ρ<0.05), while those derived according to the equation QTcV = QT + 0.087(1- RR) were the most consistent (linear regression). QTcV values were strongly correlated (r=0.83) with the QT interval and showed a coefficient of variation of 8.37% and a 95% confidence interval of 0.22-0.23 s. Owing to its simplicity and reliability, the QTcV was considered the most appropriate to be used for the correction of QT interval in dogs.

Torsades-de-Pointes associated with Taku-Tsubo cardiomyopathy following greatly reduced oxycodone use in an elderly woman

2018 ◽  
Vol 7 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Harry W. Daniell, MD
Keyword(s):  
Qt Interval ◽  
Elderly Woman ◽  
Torsades De Pointes ◽  
Gene Activity ◽  
Related Gene ◽  
Qtc Prolongation ◽  
Standard Measurement ◽  
Corrected Qt Interval ◽  
Elderly Female

This article reports an elderly female oxycodone consumer who developed Torsades-de-Pointes soon after her opioid-associated rate-corrected QT interval (QTC; a standard measurement on electrocardiograms) prolongation had been augmented by the development of Taku-Tsubo cardiomyopathy (TC), a sequence that followed greatly reduced oxycodone ingestion. Factors that likely contributed to this sequence are discussed, including direct opioid-induced inhibition of human ether-a-go-go-related gene activity and of androgen formation plus QTc prolongation induced by the presence of TC.

scholarly journals Silencing of CCR4-NOT complex subunits affects heart structure and function

2020 ◽  
Vol 13 (7) ◽  
pp. dmm044727 ◽  
Author(s):  
Lisa Elmén ◽  
Claudia B. Volpato ◽  
Anaïs Kervadec ◽  
Santiago Pineda ◽  
Sreehari Kalvakuri ◽  
...  
Keyword(s):  
Heart Development ◽  
Qt Interval ◽  
Association Studies ◽  
Induced Pluripotent Stem Cell ◽  
Interval Length ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Risk Alleles ◽  
And Function

ABSTRACTThe identification of genetic variants that predispose individuals to cardiovascular disease and a better understanding of their targets would be highly advantageous. Genome-wide association studies have identified variants that associate with QT-interval length (a measure of myocardial repolarization). Three of the strongest associating variants (single-nucleotide polymorphisms) are located in the putative promotor region of CNOT1, a gene encoding the central CNOT1 subunit of CCR4-NOT: a multifunctional, conserved complex regulating gene expression and mRNA stability and turnover. We isolated the minimum fragment of the CNOT1 promoter containing all three variants from individuals homozygous for the QT risk alleles and demonstrated that the haplotype associating with longer QT interval caused reduced reporter expression in a cardiac cell line, suggesting that reduced CNOT1 expression might contribute to abnormal QT intervals. Systematic siRNA-mediated knockdown of CCR4-NOT components in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) revealed that silencing CNOT1 and other CCR4-NOT genes reduced their proliferative capacity. Silencing CNOT7 also shortened action potential duration. Furthermore, the cardiac-specific knockdown of Drosophila orthologs of CCR4-NOT genes in vivo (CNOT1/Not1 and CNOT7/8/Pop2) was either lethal or resulted in dilated cardiomyopathy, reduced contractility or a propensity for arrhythmia. Silencing CNOT2/Not2, CNOT4/Not4 and CNOT6/6L/twin also affected cardiac chamber size and contractility. Developmental studies suggested that CNOT1/Not1 and CNOT7/8/Pop2 are required during cardiac remodeling from larval to adult stages. To summarize, we have demonstrated how disease-associated genes identified by GWAS can be investigated by combining human cardiomyocyte cell-based and whole-organism in vivo heart models. Our results also suggest a potential link of CNOT1 and CNOT7/8 to QT alterations and further establish a crucial role of the CCR4-NOT complex in heart development and function.This article has an associated First Person interview with the first author of the paper.

scholarly journals Association of severity of depression, paroxetine use and markers of liver damage with QT interval duration in patients with alcohol dependence

2020 ◽  
Vol 77 (7) ◽  
pp. 680-687
Author(s):  
Sanja Vukadinovic-Stojanovic ◽  
Zlatan Stojanovic
Keyword(s):  
Liver Damage ◽  
Qt Interval ◽  
Serum Levels ◽  
Interval Length ◽  
Gamma Glutamyl Transferase ◽  
Qtc Interval ◽  
Chronic Alcoholic ◽  
Number Of Patients ◽  
Severity Of Depression ◽  
Glutamyl Transferase

Background/Aim. Patients suffered from chronic alcoholic disease very often have depression and cardiomyopathy. Treatment with several antidepressants is associated with prolonged QT interval, ventricular arrhythmias and sudden death. The aim of this study was to investigate the relation between the severity of depression, serum levels of gamma-glutamyl transferase (GGT), as a marker of liver damage, and the possible influence of paroxetine use on duration of QT interval in patient who started treatment of chronic alcoholic dependence. Methods. The study included 147 male patients (older than 18 years of age) suffering from alcohol addiction, who were also diagnosed with depressive disorder on the basis of DSM-IV criterion and positive Hamilton Rating Scale for Depression (HRSD) at the beginning of hospitalization. Out of total number of patients, 49 were randomly selected to be treated with antidepressant paroxetine at a dose of 20 mg once daily during 20 days. The global QTc interval was automatically determined. Results. By applying the generalised linear model, the statistically significant positive correlation between the length of QTc interval and serum values of GGT, that is, intensity of alcoholism (p = 0.002) and values of the HRSD score, that is, intensity of depression (p = 0.021) was established in the sample of 147 depressed alcoholic patients before the application of paroxetine. In spite of the vulnerability of patients due to the heart damage and the liver dysfunction arising from alcohol consumption, as well as altered patients' drugs metabolism, no elongation of QTc interval resulting from the application of paroxetine was established. The length of QTc interval 20 days after paroxetine administration was 401.43 ms and before paroxetine administration it was 403.31 ms. The difference in QTc interval length (after and before paroxetine administration) was ?QTc = - 1.88 ms (p = 0.524). Conclusion. The results indicated that the severity of depression and GGT serum levels positively correlated with the length of QT interval. On the other hand, paroxetine after 20 days of usage did not prolong QT interval.

scholarly journals Associations between PM2.5 metal components and QT interval length in the Normative Aging Study

2021 ◽  
Vol 195 ◽  
pp. 110827
Author(s):  
Adjani A. Peralta ◽  
Joel Schwartz ◽  
Diane R. Gold ◽  
Brent Coull ◽  
Petros Koutrakis
Keyword(s):  
Qt Interval ◽  
Interval Length ◽  
Normative Aging Study ◽  
Aging Study ◽  
Normative Aging

scholarly journals How circadian variability of the heart rate and plasma electrolytes concentration influence the cardiac electrophysiology – model-based case study

2021 ◽  
Author(s):  
Barbara Wiśniowska ◽  
Zofia M. Bielecka ◽  
Sebastian Polak
Keyword(s):  
Heart Rate ◽  
Qt Interval ◽  
Cardiac Electrophysiology ◽  
Cardiac Activity ◽  
Diurnal Variations ◽  
Ion Concentration ◽  
Interval Length ◽  
Healthy Population ◽  
Qtc Interval ◽  
Cardiac Safety

AbstractThe circadian rhythm of cardiac electrophysiology is dependent on many physiological and biochemical factors. Provided, that models describing the circadian patterns of cardiac activity and/or electrophysiology which have been verified to the acceptable level, modeling and simulation can give answers to many of heart chronotherapy questions. The aim of the study was to assess the performance of the circadian models implemented in Cardiac Safety Simulator v 2.2 (Certara, Sheffield, UK) (CSS), as well as investigate the influence ofcircadian rhythms on the simulation results in terms of cardiac safety. The simulations which were run in CSS accounted for inter-individual and intra-individual variability. Firstly, the diurnal variations in QT interval length in a healthy population were simulated accounting for heart rate (HR) circadian changes alone, or with concomitant diurnal variations of plasma ion concentrations. Next, tolterodine was chosen as an exemplary drug for PKPD modelling exercise to assess the role of circadian rhythmicity in the prediction of drug effects on QT interval. The results of the simulations were in line with clinical observations, what can serve as a verification of the circadian models implemented in CSS. Moreover, the results have suggested that the circadian variability of the electrolytes balance is the main factor influencing QT circadian pattern. The fluctuation of ion concentration increases the intra-subject variability of predicted drug-triggered QT corrected for HR (QTc) prolongation effect and, in case of modest drug effect on QTc interval length, allows to capture this effect.

scholarly journals Associations between PM2.5 metal components and QT interval length

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
A. A. Peralta ◽  
J. Schwartz ◽  
D. R. Gold ◽  
B. Coull ◽  
P. Koutrakis
Keyword(s):  
Qt Interval ◽  
Interval Length

A presumably benign human ether-a-go-go-related gene mutation (R176W) with a malignant primary manifestation of long QT syndrome

2011 ◽  
Vol 22 (3) ◽  
pp. 360-363 ◽  
Author(s):  
Birgit C. Donner ◽  
Christoph Marshall ◽  
Klaus G. Schmidt
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Clinical Phenotype ◽  
Torsade De Pointes ◽  
Holter Monitoring ◽  
Related Gene ◽  
Long Qt ◽  
Torsade De Pointes Tachycardia ◽  
Qt Syndrome ◽  
Mild Clinical Phenotype

AbstractA 12-year-old girl presented with a first prolonged syncope. She was successfully resuscitated by external defibrillation after recording torsade de pointes tachycardia. Repeated electrocardiograms and a 12-channel Holter monitoring showed an intermittent prolongation of the QT interval. Genetic analysis identified a heterozygous point mutation in the KCNH2 gene, which is thought to be associated with a rather mild clinical phenotype of the long QT syndrome.

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