Cardiac autonomic modulation by estrogen in female mice undergoing ambulatory monitoring and in vivo electrophysiologic testing.
BACKGROUND
Estrogen is an important modulator of cardiovascular risk, but its mechanism of action is not fully understood. We investigated the effect of ovariectomy and its timing on the cardiac electrophysiology in mice.


METHODS
Thirty female mice (age 18.8 +/- 3.1 weeks) underwent in vivo electrophysiologic testing before and after autonomic blockade. Fifteen mice were ovariectomized prepuberty (PRE) and ten postpuberty (POST), 2 weeks prior to electrophysiologic testing. Five age-matched sham-operated female mice (Control) served as controls. A subset of 13 mice (5 PRE, 3 POST, and 5 Controls) underwent 24-hour ambulatory monitoring.


RESULTS
With ambulatory monitoring, the average (668 +/- 28 vs 769 +/- 52 b/min, P = 0.008) and minimum (485 +/- 47 vs 587 +/- 53 b/min, P = 0.02) heart rates were significantly slower in the ovariectomized mice (PRE and POST groups) compared to the Control group. At baseline electrophysiologic testing, there were no significant differences among the ovariectomized and intact mice in any of the measured parameters. With autonomic blockade, the Control group had a significantly larger change (delta) in the atrioventricular (AV) nodal Wenckebach (AVW) periodicity (deltaAVW = 11.3 +/- 2.9 vs 2.1 +/- 7.3 ms, P = 0.05) and functional refractory period (deltaFRP = 11.3 +/- 2.1 vs 1.25 +/- 6.8 ms, P = 0.02) compared to the ovariectomized mice. These results were not altered by the time of ovariectomy (PRE vs POST groups).


CONCLUSIONS
Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.
Saba
Samir
S
Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.savas@msx.upmc.edu
Shusterman
Vladimir
V
Usiene
Irmute
I
London
Barry
B
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology*; D015716:Electrocardiography, Ambulatory; D022062:Electrophysiologic Techniques, Cardiac; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D008955:Models, Cardiovascular; D009929:Organ Size; D010052:Ovariectomy; D011433:Propranolol / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology
D000889:Anti-Arrhythmia Agents; D004967:Estrogens; D001285:Atropine; D011433:Propranolol