Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a

Abstract

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium-handling parameters in the presence of control or bisphenol-supplemented media. A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible. Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway

“…www.nature.com/scientificreports www.nature.com/scientificreports/ In our mouse model, BPA induced heart dysfunction with reduced EF, FS, increased IVS thickness, abnormalities on cardiac electric conductivity, hypertension, and cardiac congestion. These results are in agreement with several reports describing a pro-arrhythmogenic effect of BPA in female rat hearts 9,58 and impaired cardiac function and contractility through alterations of myocyte calcium handling initiated by estrogen receptor 15 . Although only male mice were used in our study, an effect mediated by the estrogen receptor cannot be excluded entirely.…”

The Neurochemical Characterization of Parasympathetic Nerve Fibers in the Porcine Uterine Wall Under Physiological Conditions and After Exposure to Bisphenol A (BPA)

“…Moreover, processes connected with BPA-induced influence on the uterine muscles are probably similar to mechanisms taking place in the heart, in which these processes have been investigated in detail. Namely, in the heart, BPA inhibits electrical conduction (Posnack et al 2014 ), influences protein kinase A (PKA) and Ca(2+)/CaM-dependent protein kinase II (CAMKII) signaling pathways (Gao et al 2013 ), and also affects the handling of calcium ions (Ramadan et al 2018 ). Moreover, it is known that BPA may affect neuronal nicotinic receptors (Borea et al 2004 ).…”

Lights, camera, path splitter: a new approach for truly simultaneous dual optical mapping of the heart with a single camera

“…After pre-processing, a peak detector was used to measure the total number of action potentials or calcium transients in the file across time. Characteristics from each event are measured and averaged, including action potential duration, calcium transient duration, time to 90% peak, and amplitude as described previously [26, 51, 57, 58].…”