Suppression of repolarization-related arrhythmias in vitro and in vivo by low-dose potassium channel activators.
Key result
Pretreatment with low-dose pinacidil significantly reduced total ventricular ectopic beats (168 vs 582, p<0.005) and episodes of ventricular tachycardia in rabbits given cesium.
Why the study?
Do low-dose potassium channel activators suppress repolarization-related arrhythmias in preclinical models?
Population
Canine cardiac Purkinje fibers (in vitro) and anesthetized rabbits (in vivo, n=18)
Comparison
Potassium channel activators vs Vehicle (in vivo)
Design
Preclinical, randomly pretreated, double-blind fashion
Authors
Discussion
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Implication
Pinacidil and cromakalim suppress repolarization-related arrhythmias experimentally; leaves open clinical translation to long-QT syndromes.
Study Design
Type
RCT (n=18)
Blinding
double-blind
Randomization
randomly
Structured PICO
Do low-dose potassium channel activators suppress repolarization-related arrhythmias in preclinical models?
P
Population
18 anesthetized rabbits subjected to intravenous cesium to produce ventricular arrhythmias.
I
Intervention
Potassium channel activators (pinacidil and cromakalim in vitro; low-dose pinacidil 0.2 mg/kg in vivo)
C
Comparator
Vehicle (in vivo)
O
Outcome
Total ventricular ectopic beats and episodes of ventricular tachycardia (in vivo); early afterdepolarizations and triggered activity (in vitro)surrogate
Main Result
Absolute Event Rate: 168% vs 582%
p-value: p=<0.005
Low-dose potassium channel activators suppress triggered activity and arrhythmias related to prolonged repolarization in preclinical models without affecting normal action potential characteristics or blood pressure.
Cite This Study
Fish et al. (1990) conducted an RCT in cesium-induced ventricular arrhythmias (n=18). pinacidil vs. vehicle was evaluated on total ventricular ectopic beats (p=<0.005). Pretreatment with low-dose pinacidil significantly reduced total ventricular ectopic beats (168 vs 582, p<0.005) and episodes of ventricular tachycardia in rabbits given cesium.