Abstract Body: Background:
Diastolic dysfunction is a cause of significant morbidity and mortality in women after menopause. In females, increased prevalence of disease corresponds to menopause, indicating that female sex hormones protect against cardiac dysfunction. We hypothesize that female sex hormones, specifically estradiol and progesterone, improve cardiomyocyte function through improved metabolic and mechanical parameters, thus protecting against diastolic dysfunction.

Methods:
Myofibrils were isolated from cardiomyocytes of healthy female rats and treated with 100nM estradiol (E2), 4.5uM progesterone (P4), a combination solution of 100nM estradiol and 4.5uM progesterone, or vehicle (10% ethanol) for 20 minutes. Cell dynamics were measured by Ionoptix and mitochondrial respiration measured using a Seahorse XFe 96-well Bioanalyzer.

Results:
Cardiomyocytes treated with 100nM E2, 4.5uM P4, and combination showed significantly faster return velocity (+dl/dt) (Veh = 82.14+/-6.22; E2 = 135.4+/- 8.93 p = 0.007; P4 = 148.4+/-9.82 p = 0.001; Combo = 128.4 +/- 8.39 uM/s p = 0.010). Percent shortening in response to E2, P4, and combination was also higher than vehicle treated cells (Veh = 6.80+/-0.38; E2 = 10.39+/-0.61 p = 0.017; P4 = 10.37+/-0.45 p = 0.017; Combo = 9.76+/-0.47 % length p = 0.03). For mitochondrial respiration, cells treated with E2 and combination had greater maximal respiration (Veh = 147.7 +/-14.9; E2 = 248.9+/-27.1 p = 0.024; P4 = 143.3+/-36.4 ns; Combo = 236.4+/-37.65 p = 0.032) and respiratory capacity (Veh = 130.9 +/-20.0; E2 = 240.5+/-32.8 p = 0.025; P4 = 115.2+/-34.4 ns; Combo = 220.5+/-43.5 p = 0.047). None of the cells treated with P4 alone had any significant increase in respiration.

Conclusions:
Our research shows that female sex hormones such as estradiol and progesterone present in women between puberty and menopause can significantly improve both relaxation, contraction, and respiratory function of cardiomyocytes. This research demonstrates the importance of female sex hormones in cardiomyocyte function and gives insight into how the loss of such hormones can precipitate cardiac decline in postmenopausal women.