Abstract 14827: Gender Differences and Sex Hormone Effects on Electro-Mechanical Cardiac Function in Transgenic Long-QT Type 2 Rabbits
Background: Women with long QT syndrome 2 (LQT2) are at high risk for polymorphic VT and sudden cardiac death. We have previously shown pro-arrhythmic effects of estradiol (EST) and anti-arrhythmic effects of testosterone (DHT) in transgenic LQT2 rabbits due to different effects on action potential duration (APD). Also, we demonstrated diastolic dysfunction and prolonged contraction duration in LQT2 rabbits. We here aimed at analyzing gender differences and hormone effects on electro-mechanical function in LQT2.
Methods: Prepubertal male and female transgenic LQT2 rabbits underwent sham surgery (8 SM, 7 SF) or ovariectomy followed by chronic hormone (4 DHT, 4 EST) or placebo (4 OVX) therapy. In vivo phase contrast MRI were performed to analyze regional radial (Vr) and longitudinal (Vz) myocardial velocities, followed by ex vivo monophasic AP measurements in corresponding segments.
Results: Ejection fractions were normal (64±7%) in all groups. Peak systolic Vz, however, was reduced in SF and all hormone groups compared to SM (base, all p<0.0001). Peak systolic Vr were reduced in OVX (base, p<0.05 vs. EST, SF; mid, p<0.01 vs. SF, SM). Time to diastolic peak (Vr_TTP_RR_dia, Vz_TTP_RR_dia) - as marker for contraction duration - were shorter in SM than in SF, OVX and EST (p<0.01-p<0.0001). Peak diastolic Vz was lower in EST and OVX than in DHT and SM (p<0.05) and diastolic Vz was lower in OVX than in SF (p<0.05), indicating an impaired diastolic function. APDs and QT intervals (SM 189±8 ms vs. SF 203±9) tended to be shorter in SM than in SF and were significant shortened in DHT and OVX compared to SF and EST (p<0.001 vs. SF, p<0.05 vs. EST).
Conclusions: LQT2 rabbits exhibit gender differences in electro-mechanical function with prolonged TTP_dia, reduced Vz_sys, and longer APDs in SF than in SM. Gender differences were partly mimicked by sex hormones: EST reduced Vz_dia and prolonged APD, DHT and OVX shortened APD, indicating hormone effects on electrical and mechanical function in LQTS.
- © 2013 by American Heart Association, Inc.