Abstract 14969: Echocardiographic Analysis of Left Ventricular Function in Stress-Challenged Aged Mice: Effects of Gender (Sex) and Menopause
Stress-induced cardiomyopathies such as Tako-Tsubo or Broken-Heart Syndrome predominantly afflict post-menopausal women (greater than 82% of such cases) who have experienced a sudden emotional shock. These women present with symptoms mimicking a myocardial infarction, but show no significant occlusion of the coronary arteries. Instead, they display left ventricular (LV) dysfunction characterized by hypo- or a-kinetic regions, particularly near the apex. These patients often have elevated plasma catecholamines, and are at high risk of arrhythmia and sudden cardiac death if left untreated. At present, it is not entirely clear why only specific regions of the LV are primarily affected, nor is it understood why postmenopausal women are particularly susceptible to these types of stress cardiomyopathies. To investigate these questions, we first induced menopause in a group of female mice beginning around 12 months of age using 4-vinylcylcohexene diepoxide. Menopausal status was confirmed by vaginal cytology, and LV function was evaluated using high-resolution ultrasound in age-matched male and pre- and post-menopausal female mouse hearts at baseline and in response to physical restraint stress over a period of two hours. While all three groups showed similarly robust increases in heart rates, only the post-menopausal females displayed an immediate (within first 15-mins following restraint) decline in cardiac output (11.6 ± 1.5 ml/min) compared to cycling females (17.5 ± 1.8 ml/min) that was ameliorated over the two-hour duration of the experiment. In contrast, only the cycling (non-menopausal) females exhibited significant (p<0.05, n=5) decreases in diastolic volume (24.0 ± 2.8 versus 33.6 ± 2.5 μL), stroke volume (22.9 ± 2.6 versus 31.5 ± 2.3 μL) and cardiac output (15.9 ± 1.8 versus 21.7 ± 1.6 ml/min) relative to males postmenopausal females at two hours of restraint. These data demonstrate that gender (biological sex) and menopause have significant influence on LV function in response to various stressors in mice, and thus should serve as a useful biological model for uncovering the physiological basis for stress-induced cardiomyopathies.
- © 2013 by American Heart Association, Inc.