Stop the beat to see the rhythm: excitation-contraction uncoupling in cardiac research.

Optical mapping is an imaging technique that is extensively used in cardiovascular research, wherein parameter-sensitive fluorescent indicators are used to study the electrophysiology and excitation-contraction coupling of cardiac tissues. Despite many benefits of optical mapping, eliminating motion artifacts within the optical signals is a major challenge, as myocardial contraction interferes with the faithful acquisition of action potentials and intracellular calcium transients. As such, excitation-contraction uncoupling agents are frequently used to reduce signal distortion by suppressing contraction. When compared with other uncoupling agents, blebbistatin is the most frequently used, as it offers increased potency with minimal direct effects on cardiac electrophysiology. Nevertheless, blebbistatin may exert secondary effects on electrical activity, metabolism, and coronary flow, and the incorrect administration of blebbistatin to cardiac tissue can prove detrimental, resulting in erroneous interpretation of optical mapping results. In this “Getting It Right” perspective, we briefly review the literature regarding the use of blebbistatin in cardiac optical mapping experiments, highlight potential secondary effects of blebbistatin on cardiac electrical activity and metabolic demand, and conclude with the consensus of the authors on best practices for effectively using blebbistatin in optical mapping studies of cardiac tissue

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

Characteristics of Bisphenol Cardiotoxicity: Impaired Excitability, Contractility, and Relaxation

Bisphenol a (BPA) is a high production volume chemical that is frequently used to manufacture epoxy resins and polycarbonate plastics. BPA-containing products are now pervasive, and as a result, biomonitoring studies report widespread exposure in \u3e 90% of adults, adolescents, and children. Both epidemiological and experimental studies have reported associations between BPA exposure and adverse cardiovascular health outcomes. With increasing concerns regarding BPA exposure, a few structurally similar bisphenol chemicals have been introduced as replacements, including bisphenol s (BPS) and bisphenol f (BPF). In accordance with the recently established Key characteristics of cardiovascular toxicants , we reviewed the literature to highlight the immediate effects of bisphenol chemicals on (1) cardiac excitability, and (2) contractility and relaxation. BPA inhibits key cardiac ion channels, impairs cardiac excitability, and acts as a more potent inhibitor as compared to BPF and BPS. Through the inhibition of calcium current, some studies report that bisphenol chemicals can act as negative inotropic agents. Yet, others suggest that low dose exposures may increase contractility and precipitate triggered arrhythmias via the phosphorylation of key calcium handling proteins. Accordingly, we propose additional considerations for future work to comprehensively address the cardiac safety profile of BPA, as compared to replacement chemicals

Adapting to a new environment: postnatal maturation of the human cardiomyocyte

The postnatal mammalian heart undergoes remarkable developmental changes, which are stimulated by the transition from the intrauterine to extrauterine environment. With birth, increased oxygen levels promote metabolic, structural and biophysical maturation of cardiomyocytes, resulting in mature muscle with increased efficiency, contractility and electrical conduction. In this Topical Review article, we highlight key studies that inform our current understanding of human cardiomyocyte maturation. Collectively, these studies suggest that human atrial and ventricular myocytes evolve quickly within the first year but might not reach a fully mature adult phenotype until nearly the first decade of life. However, it is important to note that fetal, neonatal and paediatric cardiac physiology studies are hindered by a number of limitations, including the scarcity of human tissue, small sample size and a heavy reliance on diseased tissue samples, often without age-matched healthy controls. Future developmental studies are warranted to expand our understanding of normal cardiac physiology/pathophysiology and inform age-appropriate treatment strategies for cardiac disease

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes.

Phthalates and bisphenols are high production volume chemicals that are used in the manufacturing of consumer and medical products. Given the ubiquity of bisphenol and phthalate chemicals in the environment, biomonitoring studies routinely detect these chemicals in 75–90% of the general population. Accumulating evidence suggests that such chemical exposures may influence human health outcomes, including cardiovascular health. These associations are particularly worrisome for sensitive populations, including fetal, infant and pediatric groups—with underdeveloped metabolic capabilities and developing organ systems. In the presented article, we aimed to review the literature on environmental and clinical exposures to bisphenols and phthalates, highlight experimental work that suggests that these chemicals may exert a negative influence on cardiovascular health, and emphasize areas of concern that relate to vulnerable pediatric groups. Gaps in our current knowledge are also discussed, so that future endeavors may resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology