Slow delayed rectifier K+ current block by HMR 1556 increases dispersion of repolarization and promotes Torsades de Pointes in rabbit ventricles
Why the study?
Does I(Ks) block by HMR 1556 increase Torsades de Pointes incidence in rabbit ventricles predisposed to TdP?
Population
Bradycardic perfused rabbit ventricles (n=6 per group)
Comparison
HMR 1556 (100 nM, an I blocker) added to… vs Veratridine + dofetilide alone, or veratridine +…
Design
Preclinical
Authors
Discussion
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Member takes
Implication
I(Ks) blockade may heighten TdP risk via dispersion in vulnerable models; leaves open human translation and safety implications.
Structured PICO
Does I(Ks) block by HMR 1556 increase Torsades de Pointes incidence in rabbit ventricles predisposed to TdP?
P
Population
Bradycardic perfused rabbit ventricles (n=6 per group)
I
Intervention
HMR 1556 (100 nM, an I(Ks) blocker) added to veratridine (125 nM) and dofetilide (7.5 nM)
C
Comparator
Veratridine (125 nM) + dofetilide (7.5 nM) alone, or veratridine + dofetilide (10 nM)
O
Outcome
Incidence of spontaneous Torsades de Pointes (TdP), monophasic AP duration at 90% repolarization (MAPD90), and ECG interval between the peak and the end of T wave (Tpeak-end)surrogate
Blocking the slow delayed rectifier K+ current (I(Ks)) increases the dispersion of repolarization and promotes Torsades de Pointes in predisposed hearts, independent of further action potential prolongation.
Cite This Study
So et al. (2008) studied this question.