title: Physiological response of cardiac tissue to bisphenol A: alterations in ventricular pressure and contractility.
abstract: 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). Ca(2+) 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 Ca(2+) handling within whole hearts (reduced diastolic and systolic Ca(2+) transient potentiation) and neonatal cardiomyocytes (reduced Ca(2+) transient amplitude and prolonged Ca(2+) 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 Ca(2+) handing, and ventricular contractility.
authors.affiliation: Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia; and ngillum@gwu.edu.
authors.forename: Nikki Gillum
authors.initials: NG
authors.lastname: Posnack
authors.affiliation: Department of Biomedical Engineering, School of Engineering and Applied Sciences, The George Washington University, Washington, District of Columbia.
authors.forename: Daina
authors.initials: D
authors.lastname: Brooks
authors.affiliation: Department of Biomedical Engineering, School of Engineering and Applied Sciences, The George Washington University, Washington, District of Columbia.
authors.forename: Akhil
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Department of Biomedical Engineering, School of Engineering and Applied Sciences, The George Washington University, Washington, District of Columbia.
authors.forename: Rafael
authors.initials: R
authors.lastname: Jaimes
authors.affiliation: Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia; and.
authors.forename: Narine
authors.initials: N
authors.lastname: Sarvazyan
authors.affiliation: Department of Biomedical Engineering, School of Engineering and Applied Sciences, The George Washington University, Washington, District of Columbia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds / Q000633:toxicity*; D020013:Calcium Signaling / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010636:Phenols / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: calcium handling; cardiac; contraction; endocrine disrupting chemical; heart