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Environmental Factor, May 2012

BPA exposure traced to abnormal heart rhythms

By Thaddeus Schug

Scott Belcher, Ph.D.

Belcher is shown in his lab at UC. (Photo courtesy of Steve McCaw)

Hong-Sheng Wang, Ph.D.

Wang spoke at NIEHS in January at a meeting of grantees researching Bisphenol A (see story), where he presented his group’s findings. (Photo courtesy of Steve McCaw)

A new study (http://www.ncbi.nlm.nih.gov/pubmed/22166976)  by NIEHS grantees reports that the chemical bisphenol A (BPA), commonly found in many plastic household items, has been linked to increased frequency of arrhythmias, or heartbeat irregularities, in animals.

Plastics made with BPA are used in many consumer products, including food and beverage containers, toys, eyeglasses, computers, kitchen appliances, and medical equipment. Epoxy resins containing the chemical are used in dental work and in metal coatings for food cans, pipes, cars, dairy equipment, office equipment, and other metal products. BPA is also used in the production of certain flame retardants and as a color developer in some thermal receipt paper.

While the findings of this study are intriguing, this is only one of many NIEHS-funded studies currently underway to better understand if there are health effects related to BPA. A single study is not sufficient to make a determination about the health effects in humans.

Experiments in rats and mice

Prior to their investigation, the effects of BPA on the heart were largely unknown, according to study co-authors Scott Belcher, Ph.D., and Hong-Sheng Wang, Ph.D., from the University of Cincinnati (UC) Department of Pharmacology and Cell Biophysics. The study reports that low doses of BPA and estrogen can act alone, or in combination, to increase arrhythmias in female rats and mice. Mice and rats in the study had normal heart rhythms at baseline, before administration of BPA or the estrogen, estradiol, Belcher said.

The investigators studied heart rhythms in both the working heart and in cultured heart muscle cells. In both models, exposure to BPA increased the frequency of arrhythmias in females but not males. Administration of estrogen alone also increased the frequency of arrhythmias in females.

Arrhythmias were most frequent in the female rats and mice, when they received both BPA and estrogen at levels normally found in female humans.

"We have identified a new possible risk for female heart health, caused by increased levels of estrogens in the body and exposure to the environmental estrogen BPA," Belcher said.

Heart rhythm irregularities

Arrhythmias occur when the heart beats too slowly or too fast, or when it skips heartbeats. These heart rhythm irregularities can cause fatigue, lightheadedness, fainting, or sudden cardiac death. If a fast heart rate affects the heart's ability to pump, it can cause a heart attack.

“From a cardiac physiologist’s point of view, I think it is intriguing that a common environmental chemical can have such marked impact on the heart, as demonstrated in our study,” said Wang. Combined with recent epidemiological evidence, our work points to a potentially significant role of environmental BPA exposure in cardiovascular disease, particularly in females,” Wang added.

The rapid proarrhythmic effect of BPA was observed at very low doses, as low as subnanomolar or picomolar range, which is within the range of human BPA exposure, according to most epidemiological studies in the literature.

Citations:

Belcher SM, Chen Y, Yan S, Wang HS. (http://www.ncbi.nlm.nih.gov/pubmed/22166976)  2012. Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17beta-estradiol and the environmental endocrine disruptor bisphenol A. Endocrinology 153(2):712-720.

Yan S, Chen Y, Dong M, Song W, Belcher SM, Wang HS. (http://www.ncbi.nlm.nih.gov/pubmed/21980463)  2011. Bisphenol A and 17beta-estradiol promote arrhythmia in the female heart via alteration of calcium handling. PLoS One 6(9):e25455.

(Thaddeus Schug, Ph.D., is a health scientist in the NIEHS Division of Extramural Research and Training (DERT) and a regular contributor to the Environmental Factor.)


Graphic demonstrating how acute low dose exposures to BPA and estradiol promote arrhythmic events in female rat heart cells

These figures demonstrate how acute low dose exposures to BPA and estradiol promote arrhythmic events in female rat heart cells. (A) Low dose levels of BPA elicit spontaneous contraction in myocytes. (B) BPA exposure induces calcium transients. (C-D) Percentage of female and male myocytes with triggered activities following estradiol and BPA exposure. (Photo courtesy of Hong-Seng Wang)




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