Physiological response of cardiac tissue to bisphenol A: alterations in ventricular pressure and contractility

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility.