Key result
Female rabbit Purkinje fibers exhibited a higher incidence of dofetilide-induced early afterdepolarizations at 0.2 Hz compared to male fibers (100% vs 60%, p<0.05).
Why the study?
Does sex affect ventricular repolarization and the incidence of drug-induced early afterdepolarizations in isolated rabbit Purkinje fibers?
Population
Isolated male (n=10) and female (n=11) rabbit Purkinje fibers
Comparison
Perfusion with dofetilide (1 x 10 M) or… vs Male vs. female fibers, and comparison with…
Design
Preclinical
Follow-up
25 minutes
Authors
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Supports mechanistic basis for female TdP susceptibility; leaves open translation to human drug-induced arrhythmia risk.
Does sex affect ventricular repolarization and the incidence of drug-induced early afterdepolarizations in isolated rabbit Purkinje fibers?
Absolute Event Rate: 100% vs 60%
p-value: p=<0.05
Female rabbit Purkinje fibers exhibit longer ventricular repolarization and a higher susceptibility to drug-induced early afterdepolarizations compared to male fibers, providing a mechanistic basis for sex differences in QT interval and torsades de pointes risk.
Lu et al. (2000) studied Ventricular repolarization and drug-induced early afterdepolarizations (n=21). Dofetilide and Quinidine vs. Solvent / Male vs Female fibers was evaluated on Incidence of early afterdepolarizations with dofetilide at 0.2 Hz (p=<0.05). Female rabbit Purkinje fibers exhibited a higher incidence of dofetilide-induced early afterdepolarizations at 0.2 Hz compared to male fibers (100% vs 60%, p<0.05).
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