The adverse effects of Bisphenol A on cardiac mechanical function

Abstract

Biomonitoring studies indicate that 90% of the population is routinely exposed to Bisphenol‐A (BPA), a compound commonly found in household plastics. Environmental exposure varies between 1– 100 nM, while clinical and industrial exposure can reach 10 uM. Epidemiological studies have shown an association between increased BPA exposure and cardiovascular diseases. We aimed to test the direct effects of BPA on cardiac function using a Langendorff‐perfusion model. Excised female rat hearts were treated with 1 nM‐10 uM BPA and the resulting effects on cardiac mechanical function and calcium handling were monitored. For calcium imaging, excised hearts were treated with Blebbistatin to arrest mechanical function, and then stained with Rhod‐2, a calcium indicator dye. Epicardial calcium transients were recorded using an Andor CCD camera equipped with wavelength specific filters (570+/‐ 30 nm), and an LED spotlight (535 nm) was used for dye excitation. Calcium transients were initiated at various pacing frequencies (5Hz, 6.6Hz, and 9Hz). To assess the effect of BPA on the mechanical function of the heart, a latex balloon was inserted into the left‐ventricle to quantitate left‐ventricular developed pressure (LVDP) and maximum contractility. At high pacing frequencies, BPA decreased LVDP by 16% at 1 nM, 24% at 100nM and 36% at 10 uM, while the maximum contractility decreased by 23% at 100 nM and 33% at 10 uM. We conclude that alterations to mechanical function and calcium handling are a sensitive parameter for assessing BPA cardiac toxicity.