A Role of Preload Variability in Quantifying Cardiac Repolarization Reserve in Baseline

2016 ◽  
Vol 8 (3) ◽  
pp. 107-111
Author(s):  
Valerie Y. H. van Weperen
Keyword(s):  
Cardiac Repolarization ◽  
Repolarization Reserve

scholarly journals Interaction of different potassium channels in cardiac repolarization in dog ventricular preparations: role of repolarization reserve

2002 ◽  
Vol 137 (3) ◽  
pp. 361-368 ◽  
Author(s):  
Péter Biliczki ◽  
László Virág ◽  
Norbert Iost ◽  
Julius Gy Papp ◽  
András Varró
Keyword(s):  
Potassium Channels ◽  
Cardiac Repolarization ◽  
Repolarization Reserve

Role of Mg2+ block of the inward rectifier K+ current in cardiac repolarization reserve: A quantitative simulation

2009 ◽  
Vol 47 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Keiko Ishihara ◽  
Nobuaki Sarai ◽  
Keiichi Asakura ◽  
Akinori Noma ◽  
Satoshi Matsuoka
Keyword(s):  
Inward Rectifier ◽  
Cardiac Repolarization ◽  
Repolarization Reserve ◽  
K Current

scholarly journals The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations

2021 ◽  
Author(s):  
Leila Topal ◽  
Muhammad Naveed ◽  
Péter Orvos ◽  
Bence Pászti ◽  
János Prorok ◽  
...  
Keyword(s):  
Side Effects ◽  
Action Potentials ◽  
Oral Intake ◽  
Potassium Currents ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Cardiovascular Side Effects ◽  
Channel Inhibition ◽  
Repolarization Reserve ◽  
Electrophysiological Effects

AbstractCannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased IKr, IKs and Ito (only in dog) significantly with corresponding estimated EC50 values of 4.9, 3.1 and 5 µM, respectively, without changing IK1. Although the EC50 value of CBD was found to be higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.

Interaction of different potassium channels in dog ventricular repolarization: Role of the repolarization reserve

2002 ◽  
Vol 34 (6) ◽  
pp. A10
Author(s):  
Péter Biliczki ◽  
László Virág ◽  
Norbert Iost ◽  
Julius Gy. Papp ◽  
András Varró
Keyword(s):  
Potassium Channels ◽  
Ventricular Repolarization ◽  
Repolarization Reserve

Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na+ current in the heart

2009 ◽  
Vol 297 (3) ◽  
pp. H1048-H1057 ◽  
Author(s):  
Lin Wu ◽  
Sridharan Rajamani ◽  
Hong Li ◽  
Craig T. January ◽  
John C. Shryock ◽  
...  
Keyword(s):  
Torsade De Pointes ◽  
Polymorphic Ventricular Tachycardia ◽  
Isolated Hearts ◽  
T Wave ◽  
Dispersion Of Repolarization ◽  
Transmural Dispersion Of Repolarization ◽  
Repolarization Reserve ◽  
Monophasic Action Potentials ◽  
Transmural Dispersion

Reduction of repolarization reserve increases the risk of arrhythmia. We hypothesized that inhibition of K+ current ( IK) to decrease repolarization reserve would unmask the proarrhythmic role of endogenous, physiological late Na+ current (late INa). Monophasic action potentials (MAP) and 12-lead electrocardiogram were recorded from female rabbit isolated hearts. To block IK and reduce repolarization reserve, E-4031, 4-aminopyridine, and BaCl2 were used; to block endogenous late INa, tetrodotoxin (TTX) and ranolazine were used. E-4031 (1–60 nM) concentration-dependently prolonged MAP duration (MAPD90) and increased duration of the T wave from Tpeak to Tend (Tpeak-Tend), transmural dispersion of repolarization (TDR), and beat-to-beat variability (BVR) of MAPD90. E-4031 caused spontaneous and pause-triggered polymorphic ventricular tachycardia [ torsade de pointes (TdP)]. In the presence of 60 nM E-4031, TTX (0.6–3 μM) and ranolazine (5–10 μM) shortened MAPD90, decreased TDR, BVR, and Tpeak-Tend ( n = 9–20, P < 0.01), and abolished episodes of TdP. In hearts treated with BaCl2 or 4-aminopyridine plus E-4031, TTX (0.6–3 μM) shortened MAPD90 and decreased Tpeak-Tend. Ranolazine could not reverse the effect of E-4031 to inhibit human ether-a-go-go-related gene (HERG) K+ current; thus, the reversal by ranolazine of effects of E-4031 was likely due to inhibition of late INa and not to antagonism of the HERG-blocking action of E-4031. We conclude that endogenous, physiological late INa contributes to arrhythmogenesis in hearts with reduced repolarization reserve. Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by IK inhibitors.

scholarly journals Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs

2013 ◽  
Vol 591 (17) ◽  
pp. 4189-4206 ◽  
Author(s):  
Norbert Jost ◽  
László Virág ◽  
Philippe Comtois ◽  
Balázs Ördög ◽  
Viktória Szuts ◽  
...  
Keyword(s):  
Cardiac Repolarization ◽  
Repolarization Reserve ◽  
Ionic Mechanisms

scholarly journals Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization

2008 ◽  
Vol 295 (6) ◽  
pp. H2264-H2272 ◽  
Author(s):  
Katja E. Odening ◽  
Omar Hyder ◽  
Leonard Chaves ◽  
Lorraine Schofield ◽  
Michael Brunner ◽  
...  
Keyword(s):  
Heart Rate ◽  
Polymorphic Ventricular Tachycardia ◽  
In Vivo Model ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Drug Induced ◽  
Littermate Control ◽  
Anesthetic Agents ◽  
Anesthetic Drugs ◽  
Repolarization Reserve

Anesthetic agents prolong cardiac repolarization by blocking ion currents. However, the clinical relevance of this blockade in subjects with reduced repolarization reserve is unknown. We have generated transgenic long QT syndromes type 1 (LQT1) and type 2 (LQT2) rabbits that lack slow delayed rectifier K+ currents ( IKs) or rapidly activating K+ currents ( IKr) and used them as a model system to detect the channel-blocking properties of anesthetic agents. Therefore, LQT1, LQT2, and littermate control (LMC) rabbits were administered isoflurane, thiopental, midazolam, propofol, or ketamine, and surface ECGs were analyzed. Genotype-specific heart rate correction formulas were used to determine the expected QT interval at a given heart rate. The QT index (QTi) was calculated as percentage of the observed QT/expected QT. Isoflurane, a drug that blocks IKs, prolonged the QTi only in LQT2 and LMC but not in LQT1 rabbits. Midazolam, which blocks inward rectifier K+ current ( IK1), prolonged the QTi in both LQT1 and LQT2 but not in LMC. Thiopental, which blocks both IKs and IK1, increased the QTi in LQT2 and LMC more than in LQT1. By contrast, ketamine, which does not block IKr, IKs, or IK1, did not alter the QTi in any group. Finally, anesthesia with isoflurane or propofol resulted in lethal polymorphic ventricular tachycardia (pVT) in three out of nine LQT2 rabbits. Transgenic LQT1 and LQT2 rabbits could serve as an in vivo model in which to examine the pharmacogenomics of drug-induced QT prolongation of anesthetic agents and their proarrhythmic potential. Transgenic LQT2 rabbits developed pVT under isoflurane and propofol, underlining the proarrhythmic risk of IKs blockers in subjects with reduced IKr.

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