Estradiol promotes sudden cardiac death in transgenic long QT type 2 rabbits while progesterone is protective

2012 
Background Postpubertal women with inherited long QT syndrome type 2 (LQT2) are at increased risk for polymorphic ventricular tachycardia (pVT) and sudden cardiac death (SCD), particularly during the postpartum period. Objective To investigate whether sex hormones directly modulate the arrhythmogenic risk in LQTS. Methods Prepubertal ovariectomized transgenic LQT2 rabbits were treated with estradiol (EST), progesterone (PROG), dihydrotestosterone (DHT), or placebo (OVX). Results During 8 weeks of treatment, major cardiac events—spontaneous pVT or SCD—occurred in 5 of the 7 EST rabbits and in 2 of the 9 OVX rabbits ( P P P P P P P P 2+ oscillations resulted in early afterdepolarizations in EST-treated hearts (4 of 4), while PROG prevented SCD by eliminating this early afterdepolarization formation in 4 of the 7 hearts ( P = .058 vs EST; P Ca,L as compared with OVX ( P P Conclusion This study reveals the proarrhythmic effect of EST and the antiarrhythmic effect of PROG in LQT2 in vivo, outlining a new potential antiarrhythmic therapy for LQTS.
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