Key result
Dofetilide-induced early afterdepolarizations occurred in 67% of female, 56% of castrated male, 40% of male, and 28% of castrated female rabbit ventricular endocardium preparations.
Why the study?
Does sex and gonadal steroid status affect ventricular repolarization prolongation and arrhythmia incidence induced by IK-blocking drugs in isolated rabbit right ventricular endocardium?
Does sex and gonadal steroid status affect ventricular repolarization prolongation and arrhythmia incidence induced by IK-blocking drugs in isolated rabbit right ventricular endocardium?
Testosterone appears to protect against excess ventricular repolarization prolongation from I(Kr) blockade, while female risk involves sex-determined factors beyond estrogen.
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Rabbit tissue data on gonadal modulation of EADs warrant no clinical practice change; leaves open human translation of testosterone protection against IKr-blockade arrhythmias.
Pham et al. (2001) studied Drug-induced torsade de pointes and ventricular repolarization prolongation. Dofetilide and chromanol 293B vs. Male vs female vs castrated rabbits was evaluated on Incidence of early afterdepolarizations. Dofetilide-induced early afterdepolarizations occurred in 67% of female, 56% of castrated male, 40% of male, and 28% of castrated female rabbit ventricular endocardium preparations.
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