Effects of Acute and 2-Day Genistein Treatment on Cardiac Function and Ischemic Tolerance in Ovariectomized Rats

Background: Genistein, a naturally occurring isoflavonic phytoestrogen associated with reduced incidence of heart disease, may be a possible alternative treatment for postmenopausal women with heart disease. Objective: This study examined the effects of genistein on in vitro heart function and ischemic tolerance in ovariectomized (OVX) Sprague-Dawley rats. Methods: To examine the acute effects of genistein on cardiac function, isolated working hearts were perfused under aerobic conditions with increasing concentrations of genistein (10-150 mu M). A separate group of OVX rats was used to assess ischemic tolerance: treated rats received genistein (250 mg/kg, dissolved in 200 mu L. dimethyl sulfoxide [DMSO]) injected once daily for 2 days, and control rats received DMSO only. After treatment, hearts were perfused for 30 minutes under aerobic conditions and then subjected to 20 minutes of global no-flow ischemia by clamping the preload and afterload lines, followed by 30 minutes of reperfusion. Results: Genistein was associated with improvements in mechanical function in OVX rat hearts (n = 5) with maximum increases in contractility (259 mm Hg/sec above baseline) and cardiac output (7 mL/min above baseline) observed with 30 mu M of genistein (both, P < 0.05). Relative to baseline, genistein-treated hearts (n = 5) also had greater ischemic tolerance than did control hearts (n = 6) and significant improvements in mean (SEM) recovery of contractility (to 75.0% [9.7%] of preischemic function; P < 0.05) and cardiac output (to 48.8% [12.3%] of preischemic function; P < 0.05) after reperfusion. These effects occurred without significant changes in myocardial levels of nonprotein thiols or thiobarbituric acid reactive substances, although a reduction in mean glucose transporter protein 4 content (13.2% [2.7%]; P < 0.05) was observed in genistein-treated hearts. No significant changes in blood pressure were observed with genistein. Conclusions: Despite the lack of significant changes in physical characteristics, 2-day treatment with genistein was associated with significant cardioprotective effects in OVX rats, suggesting a potential therapeutic role in postmenopausal women. (Gend Med. 2009;6:488-497) (C) 2009 Excerpta Medica Inc.