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.

Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR-Sprague-Dawley rat: A CLARITY-BPA study

“…These analyses are a part of a larger integrated multi-investigator effort performed in parallel with the comprehensive GLP-compliant 2-year CLARITY-BPA chronic exposure study investigating the toxicity of BPA (21, 24). The premise for analysis of these cardiac endpoints was derived from accumulating evidence indicating that the heart is a target for the effects of the endocrine disrupting chemical BPA (16–19, 37). While the heart of both males and females express estrogen receptors (38), the impacts of ER activation by estradiol and the disruptive actions of BPA in the heart are sex specifically regulated and often differ in males and females (12, 13, 17–19).…”

“…These estrogen-like effects of BPA increased arrhythmia frequencies in response to β-adrenergic stress in isolated hearts from female rats and mice, but not those of males (13). Additional in vitro studies have also demonstrated that acute exposures to high concentrations of BPA could decrease the rate and force of contractility and cardiac conduction velocity in hearts from female rats (14, 15) and to a lesser extent in the male heart (16). In vivo studies involving analysis of large numbers of male and female CD-1 or C57Bl/6n mice exposed throughout life to a wide range of BPA doses have also identified a number of sex and strain specific exposure-related effects (17–19).…”

Functional response of the isolated, perfused normoxic heart to pyruvate dehydrogenase activation by dichloroacetate and pyruvate

“…Isovolumic LVDP was measured by inserting a latex balloon (size 5) into the LV using established techniques [17, 41]. The balloon was attached to a pressure transducer and the diastolic LV pressure was set to 10 mmHg using a spindle syringe.…”

“…Neonatal rat ventricular myocytes were isolated and plated from a heterogeneous population of hearts, as previously described [41, 42]. Intracellular Ca 2+ transients were imaged using Fluo-4 and confocal fluorescence microscopy [42].…”

Bisphenols as a Legacy Pollutant, and Their Effects on Organ Vulnerability

“…Several studies have established the role of bisphenol in cardiovascular diseases, including myocardial infarction, cardiomyopathy, and hypertensive heart disease [105][106][107][108][109]. A survey conducted in the United States shows the correlation between urinary BPA levels and increased prevalence of heart disease [84].…”