scholarly journals In Silico Assessment of Class I Antiarrhythmic Drug Effects on Pitx2-Induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues

2021 ◽  
Vol 22 (3) ◽  
pp. 1265
Author(s):  
Jieyun Bai ◽  
Yijie Zhu ◽  
Andy Lo ◽  
Meng Gao ◽  
Yaosheng Lu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antiarrhythmic Drugs ◽  
Drug Effects ◽  
Ionic Currents ◽  
Tissue Level ◽  
Drug Binding ◽  
Class I ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Upstroke Velocity

Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action po-tential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmaco-logical effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax), and decreased AP duration (APD), conduction velocity (CV), and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that disopyramide may be more effective against Pitx2-induced AF than propafenone and quinidine by prolonging WL.

scholarly journals In Silico Assessment of Class I Antiarrhythmic Drugs Effects on Pitx2-induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues

2020 ◽  
Author(s):  
Jieyun Bai ◽  
Yijie Zhu ◽  
Andy Lo ◽  
Meng Gao ◽  
Yaosheng Lu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antiarrhythmic Drugs ◽  
Ionic Currents ◽  
Tissue Level ◽  
Drug Binding ◽  
Class I ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Atrial Cells ◽  
Upstroke Velocity

Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)‐dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to Class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action potential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax) and conduction velocity (CV), and decreased AP duration (APD) and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that quinidine and disopyramide may be more effective against Pitx2-induced AF than propafenone by prolonging WL.

CHECKING THE ASSOCIATION OF FIVE SNP WITH UNVALVED ATRIAL FIBRILLATION IN PATIENTS WITH ACUTE CORONARY SYNDROME

2021 ◽  
pp. 42-52
Author(s):  
Lozhkina N.G. ◽  
Gurazheva A.A. ◽  
Maksimov V.N.
Keyword(s):  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Acute Coronary Syndrome Patient ◽  
Study Groups ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Male Patients ◽  
European Society Of Cardiology

Вackground. It is known that 5–21% of patients with acute coronary syndrome (ACS) develop atrial fibrillation (AF), which entails an increased risk of recurrence of myocardial infarction, heart failure, and increased mortality. The genetic predisposition to AF has been actively studied in recent years, but the data on the association of certain single nucleotide polymorphisms (SNPs) in the development of AF are contradictory, which determines the relevance of this study. Purpose of the study. To study five SNPs for associations with the development of non-valvular atrial fibrillation in patients with acute coronary syndrome Patient Characterization and Research Methods. The study included female and male patients not younger than 18 years old with ACS and AF (n = 133) and ACS without AF (n = 133) ACS was diagnosed according to the criteria of the European Society of Cardiology (2015; 2017). The study was approved by the Ethics Committee (Minutes No. 102 dated November 24, 2017). The observation period was 12 months. In addition to the standard examination, all patients underwent a SNP study: rs6795970 (Scn10a), rs2200733 (4th stage), rs11556924 (ZC3HC1), rs599839 (PSRC1), rs10824026 (10th stage). Statistical analysis was performed using Statistica 12.1 StatSoft. Results. The results of the rs599839 study showed that the GG genotype was significantly less common in the ACS + AF group compared to the ACS group without AF (OR 0.11 CI 95% 0.01; 0.86 p = 0.0163). A reliable connection was lost when divided by sex and by age (older and younger than 55). Allele G rs599839 significantly correlates with AF (p = 0.0043; OR 1.56). The T allele rs11556924 is highly reliably associated with a predisposition to atrial fibrillation (p = 0.0043; OR 1.93). Genotype GG rs10824026 is conditionally protective in terms of the risk of AF in patients with ACS. For rs6795970 (p = 0.290) and rs2200733 (p = 0.30), there were no statistically significant differences between the study groups. Conclusion. The study verified the association of rs6795970 (Scn10a), rs2200733, rs11556924, rs599839, rs10824026 with AF associated with ACS. The genotypes GG rs599839 and GG rs10824026 were found to be conditionally protective in relation to the risk of AF in patients with ACS.

scholarly journals Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation

2020 ◽  
Author(s):  
Mazhar Warraich ◽  
Christina Peter ◽  
Mahmood Ahmad ◽  
Shazaib Sheikh ◽  
George R Abraham ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Antiarrhythmic Drugs ◽  
Class I

Inhibition of IK,ACh current may contribute to clinical efficacy of class I and class III antiarrhythmic drugs in patients with atrial fibrillation

2009 ◽  
Vol 381 (3) ◽  
pp. 251-259 ◽  
Author(s):  
Niels Voigt ◽  
Nadiia Rozmaritsa ◽  
Anne Trausch ◽  
Thomasz Zimniak ◽  
Torsten Christ ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Efficacy ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
Class Iii

scholarly journals 3321 European Ancestry as a Risk Factor for Atrial Fibrillation in Puerto Rican Hispanics

2019 ◽  
Vol 3 (s1) ◽  
pp. 10-11
Author(s):  
Ariel Gonzalez-Cordero ◽  
Jorge Duconge-Soler ◽  
Ángel López-Candales
Keyword(s):  
Atrial Fibrillation ◽  
Risk Factor ◽  
Single Nucleotide Polymorphisms ◽  
Puerto Rican ◽  
Population Sample ◽  
European Ancestry ◽  
Genetic Admixture ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

OBJECTIVES/SPECIFIC AIMS: Consequently, we have decided to evaluate the presence of single nucleotide polymorphism (SNP) previously associated with AF on a European-descent population in an attempt to first identify the most common loci present in the PRH population and then search for specific PRH SNP associated with AF. METHODS/STUDY POPULATION: A secondary analysis of a Puerto Rican population sample (n = 120) from The Pharmacogenetics of Warfarin in Puerto Ricans Study will be performed. We will implement data from the 1000 genome project to establish a control group of healthy PRH population. Will evaluate the presence of 111 known single nucleotide polymorphisms associated with AF in Europeans and determine the frequency in PRH population sample, and validate predictability of such SNPs. Using admixture informatic markers (AIM) analysis will determine the percentage of admixture by Yoruba, Native American and Iberic-European. Statistical analysis will include the use of the Pearson Product-Moment Coefficient correlation analysis and multivariate linear regression. For admixture will use Maximum Likelihood Estimation and Markov Chain Monte Carlo models. RESULTS/ANTICIPATED RESULTS: A higher frequency of AF associated European single nucleotide polymorphisms, and an overall higher percentage of European admixture will be associated with atrial fibrillation in Puerto Rican Hispanic patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Our contributions here are expected to be the elucidation of European ancestry as a risk factor for AF. These contributions will be significant because it can provide a robust scientific basis for larger GWAS studies in the Puerto Rican community and further narrow down the mechanism specific to this population. Research in this subject could lead to early identification of patients with high risk of developing atrial fibrillation and further decrease incidence and disease burden in the PRH population. Puerto Rican Hispanics have an exclusive genetic admixture that makes for an appealing research subject that could deliver unique results.

scholarly journals Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

2017 ◽  
Vol 95 (11) ◽  
pp. 1313-1318 ◽  
Author(s):  
Ursula Ravens
Keyword(s):  
Atrial Fibrillation ◽  
Drug Targets ◽  
Antiarrhythmic Drugs ◽  
Drug Effects ◽  
K Channel ◽  
Channel Blockers ◽  
Electrophysiological Properties ◽  
Cardiac Functions ◽  
K2p Channels ◽  
Pore Domain

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting IKur, the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting IK,ACh, the Ca2+-activated K+ channels of small conductance (SK) conducting ISK, and the two-pore domain K+ (K2P) channels (tandem of P domains, weak inward-rectifying K+ channels (TWIK-1), TWIK-related acid-sensitive K+ channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents ITWIK-1, ITASK-1, and ITASK-3. Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

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