QTU-Prolongation and Torsades de Pointes Induced by Putative Class III Antiarrhythmic Agents in the Rabbit

1990 ◽  
Vol 16 (2) ◽  
pp. 276-285 ◽  
Author(s):  
Leif Carlsson ◽  
Olle Almgren ◽  
Goran Duker
Keyword(s):  
Torsades De Pointes ◽  
Antiarrhythmic Agents ◽  
Class Iii

scholarly journals Cardioversion of recent-onset atrial fibrillation using intravenous antiarrhythmics

2021 ◽  
Author(s):  
Samuel Levy
Keyword(s):  
Atrial Fibrillation ◽  
Real Life ◽  
Torsades De Pointes ◽  
Antiarrhythmic Agents ◽  
Success Rates ◽  
Class Iii ◽  
Recent Onset ◽  
New Class ◽  
Pharmacological Cardioversion ◽  
Onset Atrial Fibrillation

ABSTRACT (195 words) Pharmacological cardioversion using intravenous antiarrhythmic agents is commonly indicated in symptomatic patients with recent-onset atrial fibrillation (AF). Except in hemodynamically unstable patients who require emergency direct current electrical cardioversion, for the majority of hemodynamically stable patients, pharmacological cardioversion represents a valid option and requires the clinician to be familiar with the properties and use of antiarrhythmic agents. The main characteristics of selected intravenous antiarrhythmic agents for conversion of recent-onset AF, the reported success rates and possible adverse events are discussed. Among intravenous antiarrhythmics, flecainide, propafenone, amiodarone, sotalol, dofetilide, ibutilide and vernakalant are commonly used. Antazoline, an old antihistaminic agent with antiarrhythmic properties was also reported to give encouraging results. Intravenous flecainide and propafenone are the only class I agents still recommended by recent guidelines. Intravenous new class III agents as dofetilide and ibutilide have high and rapid efficacy in converting AF to sinus rhythm but require strict surveillance with ECG monitoring during and after intravenous administration because the potential risk of QT prolongation and Torsades de Pointes which can be prevented and properly managed. Vernakalant, a partial atrial selective was shown to have a high success rate and to be safe in real life use.

scholarly journals QTc-prolonging drugs and the risk of sudden death

Medicina ◽  
2007 ◽  
Vol 43 (4) ◽  
pp. 347 ◽  
Author(s):  
Dagmara Reingardienė ◽  
Jolita Vilčinskaitė
Keyword(s):  
Sudden Death ◽  
Qt Interval ◽  
Antimicrobial Agents ◽  
Antidepressant Drugs ◽  
Torsades De Pointes ◽  
Qt Prolongation ◽  
Polymorphic Ventricular Tachycardia ◽  
Antiarrhythmic Agents ◽  
Class Iii ◽  
Increased Risk

Various drugs can be associated with QT prolongation. A prolonged QT interval leads to an increased risk for the development of ventricular tachyarrhythmias, particularly polymorphic ventricular tachycardia (torsades de pointes). Polymorphic arrhythmia may rapidly develop into ventricular fibrillation and cause sudden death. Torsades de pointes is classically associated with early depolarization. This review article discusses the mechanisms of QTc prolongation and triggering factors for proarrhythmia, drugs that prolong QT interval (class III antiarrhythmic agents, antimicrobial agents – fluoroquinolone and macrolide antibiotics, antipsychotic and antidepressant drugs, agents used in general anesthesia, antimycotics, and several other drugs), nonpharmacological and pharmacological risk factors for arrhythmias (due to pharmacokineticpharmacodynamic interactions), the treatment and recommendations to prevent arrhythmia related to QT prolongation.

scholarly journals Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.

1990 ◽  
Vol 96 (1) ◽  
pp. 195-215 ◽  
Author(s):  
M C Sanguinetti ◽  
N K Jurkiewicz
Keyword(s):  
Antiarrhythmic Agent ◽  
Reversal Potential ◽  
Differential Sensitivity ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Antiarrhythmic Agents ◽  
Class Iii ◽  
Activation Curve ◽  
Voltage Range ◽  
K Current

An envelope of tails test was used to show that the delayed rectifier K+ current (IK) of guinea pig ventricular myocytes results from the activation of two outward K+ currents. One current was specifically blocked by the benzenesulfonamide antiarrhythmic agent, E-4031 (IC50 = 397 nM). The drug-sensitive current, "IKr" exhibits prominent rectification and activates very rapidly relative to the slowly activating drug-insensitive current, "IKs." IKs was characterized by a delayed onset of activation that occurs over a voltage range typical of the classically described cardiac IK. Fully activated IKs, measured as tail current after 7.5-s test pulses, was 11.4 times larger than the fully activated IKr. IKr was also blocked by d-sotalol (100 microM), a less potent benzenesulfonamide Class III antiarrhythmic agent. The activation curve of IKr had a steep slope (+7.5 mV) and a negative half-point (-21.5 mV) relative to the activation curve of IKs (slope = +12.7 mV, half-point = +15.7 mV). The reversal potential (Erev) of IKr (-93 mV) was similar to EK (-94 mV for [K+]o = 4 mM), whereas Erev of IKs was -77 mV. The time constants for activation and deactivation of IKr made up a bell-shaped function of membrane potential, peaking between -30 and -40 mV (170 ms). The slope conductance of the linear portion of the fully activated IKr-V relation was 22.5 S/F. Inward rectification of this relation occurred at potentials greater than -50 mV, resulting in a voltage-dependent decrease in peak IKr at test potentials greater than 0 mV. Peak IKr at 0 mV averaged 0.8 pA/pF (n = 21). Although the magnitude of IKr was small relative to fully activated IKs, the two currents were of similar magnitude when measured during a relatively short pulse protocol (225 ms) at membrane potentials (-20 to +20 mV) typical of the plateau phase of cardiac action potentials.

scholarly journals Antiarrhythmic and cardiac electrophysiological effects of SZV-270, a novel compound with combined Class I/B and Class III effects, in rabbits and dogs

2020 ◽  
Author(s):  
Richard S Varga ◽  
Tibor Hornyik ◽  
Zoltán Husti ◽  
Zsófia Kohajda ◽  
Gábor Krajsovszky ◽  
...  
Keyword(s):  
Torsades De Pointes ◽  
Coronary Artery Occlusion ◽  
Canine Model ◽  
Artery Occlusion ◽  
Class I ◽  
Class Iii ◽  
Drug Induced ◽  
Pharmacological Management ◽  
Repolarization Reserve ◽  
Electrophysiological Effects

Cardiovascular diseases are the leading causes of mortality. Sudden cardiac death is most commonly caused by ventricular fibrillation (VF). Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of stroke and heart failure. Pharmacological management of VF and AF remains suboptimal due to limited efficacy of antiarrhythmic drugs and their ventricular proarrhythmic adverse effects. In this study, the antiarrhythmic and cardiac cellular electrophysiological effects of SZV-270, a novel compound, were investigated in rabbit and canine models. SZV-270 significantly reduced the incidence of VF in rabbits subjected to coronary artery occlusion/reperfusion, reduced the incidence of burst-induced AF in a tachypaced conscious canine model of AF. SZV-270 prolonged frequency corrected QT interval, lengthened action potential duration and effective refractory period in ventricular and atrial preparations and blocked IKr in isolated cardiomyocytes (Class III effects), reduced maximum rate of depolarization (Vmax) at cycle lengths smaller than 1000 ms in ventricular preparations (Class I/B effect). Importantly, SZV-270 did not provoke Torsades de Pointes arrhythmia in an anesthetized rabbit proarrhythmia model characterized by impaired repolarization reserve. In conclusion, SZV-270 with its combined Class I/B and III effects can prevent re-entry arrhythmias with reduced risk of provoking drug-induced Torsades de Pointes.

Abstract MP44: Biomarker Measures of Fish-Derived Omega-3 Fatty Acids and J-Point Elevation in the Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Noelle N Gronroos ◽  
Pamela J Schreiner ◽  
Elsayed Z Soliman ◽  
Lisa Harnack ◽  
Richard F MacLehose ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linear Trend ◽  
Antiarrhythmic Agents ◽  
Omega 3 ◽  
Class Iii ◽  
Atherosclerosis Risk In Communities ◽  
Surface Ecg ◽  
Atherosclerosis Risk ◽  
Aric Study

Background: Higher intake of fish-derived omega-3 polyunsaturated fatty acids (PUFAs) has been associated with lower incidence of Sudden Cardiac Death (SCD), but the exact mechanisms underlying this association are unconfirmed. Early ventricular repolarization characterized by an elevation of the QRS-ST junction (J-Point) in the surface ECG has been associated with idiopathic ventricular fibrillation, the most common cause of SCD. We aimed to study the association of fish-derived PUFAs in plasma with the prevalence of J-Point elevation. Methods: We conducted a cross-sectional analysis of participants aged 45-64 (45.7% male, 100% whites) from the Minnesota Field Center of the Atherosclerosis Risk in Communities (ARIC) Study. Participants were excluded if they did not have an ECG, had a QRS duration ≥ 120 ms, were taking Class I or Class III antiarrhythmic agents, or had prevalent cardiovascular disease. Fish-derived PUFAs were measured in plasma phospholipids as a percentage of total fatty acids, categorized into quartiles, and logistic regression was used to estimate the odds of J-Point Elevation, defined as elevation of greater than 100 microvolts in at least two contiguous leads. Models were adjusted for potential confounders and tests of linear trend were conducted by assigning the median values for each exposure category and modeling as a continuous variable. Results: Among 3,330 eligible individuals, 126 presented J-Point elevation. Median fish-derived fatty acid percentage was 3.2% (range: 0.7-12.2). Using multivariable analyses, plasma measures of fish-derived omega-3 PUFAs were linearly associated with the log odds of J-Point elevation with increasing fatty acid percentages associated with lower odds of J-Point elevation (see Table). Conclusions: In this population, higher plasma levels of fish-derived PUFAs were inversely associated with J-Point elevation. Fish-derived PUFAs could reduce risk of SCD through decreased prevalence of early repolarization.

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