Environmental chemicals can disrupt neonatal cardiomyocyte physiology

Abstract

BackgroundThe ubiquitous nature of plastics has raised concerns pertaining to continuous exposure to plastic polymers and human health risks. Of particular concern is the use of endocrine‐disrupting chemicals in plastic production, including bisphenol A (BPA). Widespread and continuous exposure to BPA can occur through dietary intake, inhalation, dermal and intravenous exposure via consumer products and medical devices. Recent studies have shown a link between BPA exposure and adverse cardiovascular outcomes. This is particularly concerning for vulnerable populations who are at risk of high BPA exposure due to medical treatment, including pediatric patients. Despite significant differences in the cardiac physiology of the developing and adult heart, our current understanding of BPA‐induced cardiac dysfunction has been limited to adult models.ObjectiveCardiac physiology differs significantly between the pediatric and adult heart. We aimed to determine the extent to which BPA exposure contributes to cardiovascular dysfunction, using a neonatal cardiomyocyte model.MethodsNeonatal rat ventricular myocytes (NRVM) were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium‐handling in the presence of control or bisphenol‐supplemented media. A range of environmental and clinically‐relevant exposure levels were tested [10−9 – 10−5M].ResultsAcute BPA exposure (15 – 20 min) altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability beginning at low concentrations (10−8M BPA). BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes and prolonged calcium transient duration time, which replicated our previously published studies in isolated‐whole hearts. BPA‐induced changes in calcium handling increased the propensity for calcium transient alternans, beginning at low BPA concentrations (10−9M). The observed alterations in calcium kinetics following BPA exposure were not the result of cytotoxicity or altered cell viability.ConclusionOur studies show that acute BPA chemical exposure can alter neonatal cardiomyocyte physiology. Additional studies are necessary to determine the effects of bisphenol exposure on pediatric heart electrophysiology and mechanical function, as well as the impact of long‐term treatment that more closely mimics clinical exposure.Support or Funding InformationThis publication was supported by the National Institutes of Health (R00ES023477, UL1TR000075), Children's Research Institute and Children's National Heart Institute.