Double pharmacological challenge on repolarization opens new avenues for drug safety research

British Journal of Pharmacology

Volumn 151, Issue 7, 2007, Pages 909-911

  Thomsen, M B ^a  

^a Columbia University ^*  (United States)

Author keywords

Action potential; Beat to beat variability of repolarization; Drug research; Electrophysiology; Long QT; Proarrhythmia; Repolarization reserve; Torsades de pointes

Indexed keywords

DOFETILIDE; N [3 HYDROXY 2,2 DIMETHYL 6 (4,4,4 TRIFLUOROBUTOXY)CHROMAN 4 YL] N METHYLMETHANESULFONAMIDE;

CARDIOVASCULAR RISK; DISEASE MARKER; DOG; DRUG INDUSTRY; DRUG RESEARCH; DRUG SAFETY; DRUG SCREENING; HEART PROARRHYTHMIA; HEART REPOLARIZATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; TORSADE DES POINTES;

ANIMALS; CHROMANS; DELAYED RECTIFIER POTASSIUM CHANNELS; DOGS; DRUG SYNERGISM; DRUG TOXICITY; ELECTROCARDIOGRAPHY; HUMANS; LONG QT SYNDROME; PHENETHYLAMINES; POTASSIUM CHANNEL BLOCKERS; POTASSIUM CHANNELS, VOLTAGE-GATED; RABBITS; RISK FACTORS; SULFONAMIDES; TORSADES DE POINTES;

EID: 34547607863     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/sj.bjp.0707299     Document Type: Review

References (13)

1. Biliczki P, Virag L, Iost N, Papp JG, Varro A (2002). Interaction of different potassium channels in cardiac repolarization in dog ventricular preparations: role of repolarization reserve. Br J Pharmacol 137: 361-368.
2. Burashnikov A, Antzelevitch C (2002). Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations. J Cardiovasc Electrophysiol 13: 172-177.
3. Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C et al. (2000). The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology. Cardiovasc Res 47: 219-233.
4. Jost N, Virag L, Bitay M, Takacs J, Lengyel C, Biliczki P et al. (2005). Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle. Circulation 112: 1392-1399.
5. Ks increases short-term QT interval variability and provokes torsades de pointes. Br J Pharmacol 151: 941-951 (this issue).
6. So PP, Hu XD, Backx PH, Puglisi JL, Dorian P (2006). Blockade of IKs by HMR 1556 increases the reverse rate-dependence of refractoriness prolongation by dofetilide in isolated rabbit ventricles. Br J Pharmacol 148: 255-263.
7. Thomsen MB, Matz J, Volders PG, Vos MA (2006). Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias. Pharmacol Ther 112: 150-170.
8. Thomsen MB, Oros A, Schoenmakers M, van Opstal JM, Maas JN, Beekman JD et al. (2007). Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation. Cardiovasc Res 73: 521-530.
9. Thomsen MB, Verduyn SC, Stengl M, Beekman JD, de Pater G, van Opstal J et al. (2004). Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation 110: 2453-2459.
10. van der Linde H, Van de Water A, Loots W, Van Deuren B, Lu HR, Van Ammel K et al. (2005). A new method to calculate the beat-to-beat instability of QT duration in drug-induced long QT in anesthetized dogs. J Pharmacol Toxicol Methods 52: 168-177.
11. Varro A, Balati B, Iost N, Takacs J, Virag L, Lathrop DA et al. (2000). The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization. J Physiol 523 (part 1): 67-81.
12. Volders PG, Stengl M, van Opstal JM, Gerlach U, Spatjens RL, Beekman JD et al. (2003). Probing the contribution of IKs to canine ventricular repolarization: key role for beta-adrenergic receptor stimulation. Circulation 107: 2753-2760.
13. Wu L, Shryock JC, Song Y, Belardinelli L (2006). An increase in late sodium current potentiates the proarrhythmic activities of low-risk QT-prolonging drugs in female rabbit hearts. J Pharmacol Exp Ther 316: 718-726.