Bisphenol A exposure and cardiac electrical conduction in excised rat hearts

BACKGROUND: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown. OBJECTIVES: The goal of our studies was to measure BPA\u27s effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats. METHODS: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. RESULTS: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1 - 100 μM), prolonged action potential duration (1 - 100 μM) and delayed atrioventricular conduction (10 - 100 μM). Importantly, these effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals, dropped ventricular beats and eventually resulted in complete heart block. CONCLUSIONS: Our results show that acute BPA exposure slows electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA\u27s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause/exacerbate conduction abnormalities in patients with pre-existing heart conditions and other high-risk populations

Optogenetic control of cardiac autonomic neurons in transgenic mice

© Springer Science+Business Media, LLC, part of Springer Nature 2021. Optogenetic technology has enabled unparalleled insights into cellular and organ physiology by providing exquisite temporal and spatial control of biological pathways. Here, an optogenetic approach is presented for selective activation of the intrinsic cardiac nervous system in excised perfused mouse hearts. The breeding of transgenic mice that have selective expression of channelrhodopsin in either catecholaminergic or cholinergic neurons is described. An approach for perfusing hearts excised from those animals, recording the ECG to measure heart rate changes, and an illumination technique using a custom micro-LED light source to activate channelrhodopsin is explained. We have used these methods in ongoing studies of the kinetics of autonomic control of cardiac electrophysiology and contractility, demonstrating the proven utility of optogenetic technology to enable unparalleled spatiotemporal anatomic-functional probing of the intrinsic cardiac nervous system