Effects of estrogen on cardiac electrophysiology in female mice.
BACKGROUND
Understanding the molecular mechanisms that underlie gender- and hormonal-related differences in susceptibility to cardiac arrhythmias has been hampered by the lack of a suitable animal model. We examined the effect of hormonal status on the electrophysiologic (EP) properties of the mouse heart in an in vivo, closed chest model.


RESULTS
Fifty-three female C57/J mice aged 10 to 12 weeks were studied. Thirty-six mice underwent bilateral ovariectomies; 18 received estrogen (OVX+E) and 18 received placebo (OVX). Seventeen female mice underwent only sham surgery. All animals underwent in vivo EP studies. Select EP parameters were measured after quinidine treatment. Data were analyzed by a blinded observer. Compared with the intact female mice, the PR and AH intervals were significantly shorter in the OVX mice, and these parameters normalized with estrogen replacement (PR = 45.9+/-4.5 msec in the intact mice, 42.1+/-4.3 msec in the OVX group, and 46.9+/-3.5 msec in the OVX+E group, P < 0.005; AH = 36.5+/-4.9 msec in the intact mice, 34.4+/-4.7 msec in the OVX group, and 38.8+/-2.7 msec in the OVX+E group, P = 0.03). The right ventricular effective refractory period was significantly shorter in the OVX mice versus the intact mice, and this also normalized with estrogen replacement. Hormonal status did not significantly affect any other EP variable, including QT interval.


CONCLUSIONS
In female mice, estrogen prolongs AV nodal conduction and the right ventricular effective refractory period. Taken together, these data suggest that hormonal status affects aspects of cardiac EP function. Future application of this mouse model will be helpful in determining the molecular pathways that mediate hormonal differences in cardiac EP.
Saba
Samir
S
Molecular Cardiology Research Institute, New England Cardiac Arrhythmia Center, Tufts University-New England Medical Center, Boston, Massachusetts 02111, USA.
Zhu
Wei
W
Aronovitz
Mark J
MJ
Estes
N A Mark
NA
Wang
Paul J
PJ
Mendelsohn
Michael E
ME
Karas
Richard H
RH
D000704:Analysis of Variance; D000818:Animals; D001283:Atrioventricular Node / Q000502:physiology*; D004594:Electrophysiology; D004958:Estradiol / Q000502:physiology*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D012008:Recurrence; D016278:Ventricular Function, Right / Q000502:physiology*
D004958:Estradiol