. Importantly, this is the first study that has identified an association
between MEHP exposure and cardiac rhythm abnormalities.
study, published in Circulation:
Arrhythmia and Electrophysiology
, was led by Dr. Nikki Posnack, PhD, who is a
Principal Investigator with the Sheikh Zayed Institute for Pediatric Surgical
Innovation at the Children's Research Institute and an Assistant Professor of
Pharmacology & Physiology, George Washington University School of Medicine
and Health Sciences, Washington DC, USA.
The first author of
the paper was Dr. Rafael Jaimes, PhD, who is a Staff Scientist at the
Children's Research Institute, Washington DC, USA.
Phthalate and Its Effect on Health
esters of phthalic acid, which are primarily used as plasticizers. The main
function of plasticizers is to soften plastics such as polyvinyl chloride
(PVC). They make plastics more malleable, flexible, durable, and transparent.
common types of phthalates
are mono-(2-ethylhexyl) phthalate (MEHP) and
di-(2-ethylhexyl) phthalate (DEHP). DEHP is commonly used to make plastics more
soft and pliable, which are used in medical accessories such as plastic tubing.
It should be noted that DEHP accounts for 40 percent of the weight of plastic
bags used for storing blood and 80 percent of the weight of plastic tubes,
used for assisted feeding, artificial respiration, and catheters for cardiac
industrial usefulness, it has been documented based on epidemiological studies
that phthalates can have adverse effects on health. Studies have shown that
exposure to phthalates can lead to inflammatory conditions, metabolic
disturbances, neurological disorders, reproductive problems, as well as cardiac
Background of the Study
The present study
is based on previous studies conducted by the same research group. These
studies revealed that in cardiomyocyte models, the cellular electrical coupling
was reduced by exposure to DEHP, which slowed the conduction velocity of
electrical impulses, resulting in the development of arrhythmia.
using microarrays showed that DEHP treatment of cardiomyocytes led to changes
in the levels of mRNA, which affected calcium transport, resulting in
abnormalities in cardiac muscle contraction. Another preclinical study found
that DEHP interfered with the regulation of cardiovascular function by the
The major findings
are highlighted below:
"We chose to study the impact of MEHP exposure on
cardiac electrophysiology at concentrations that are observed in an intensive
care setting, since plastic medical products are known to leach these chemicals
into a patient's bloodstream,"
of in vitro heart models for 30
minutes to MEHP, a metabolite to DEHP, resulted in an increased risk of
irregular heart rhythms
effect of 60 µM of MEHP (equivalent to that present in stored blood used
for pediatric blood transfusions) on the heart was studied
to MEHP for 30 minutes reduced atrioventricular (AV) conduction velocity
and increased AV node effective refractory period
prolonged action potential duration and increased action potential
increased the ventricular effective refractory period
reduced the epicardial conduction velocity
says Posnack. "In critical conditions, a patient may
have a blood transfusion, require extracorporeal membrane
oxygenation, undergo cardiopulmonary bypass or require dialysis or intravenous
fluid administration. All of these scenarios can lead to plastic chemical
exposure. Our research team wants to investigate how these plastic chemicals
can impact cardiac health."
Explanation of the Study Findings
Phthalates have a
similar chemical structure to hormones, as a result of which they can interfere
with various biological processes. These low molecular weight chemicals are
capable of interacting with ion channels, cell membrane receptors, nuclear
receptors, as well as other targets in the cell. For example, they can cause
inhibition of NaV1.5 voltage-gated sodium (Na) channels present in
cardiomyocytes, which disrupts the flow of Na+
ions through these
channels. These types of interactions could explain the changes observed in the
preclinical heart models.
Implications of the Study
researchers at the Division of Cardiovascular Medicine, University of
Wisconsin-Madison in an accompanying Editorial entitled "Shocking Aspects of Nonconductive Plastics"
, note that
although the clinical effects of plasticizers on the heart still needs to be
studied in greater detail, the findings of the present study adds to the
accumulating evidence that MEHP and DEHP are not inert, but possess chemical
"Toxic plasticizers in children's toys and baby
products hit public headlines 20 years ago, but exposure to these
compounds is up to 25x higher in patients undergoing complex medical
write the University of Wisconsin-Madison researchers. "We readily (and unknowingly) administer
these compounds, and at times in high quantity, to some of our most vulnerable
patients. This work highlights the need for further investigation into short
and long-term plasticizer exposure on cardiac electrophysiology."
The research team
plans to build upon their current findings by using larger preclinical models
and eventually carry out human testing. They plan to use stem cell-derived
cardiomyocytes to compare the activities of plastic chemicals with other
alternatives in order to assess their safety profile.
Concluding Remarks "It's important to note that this was a preliminary
study performed on an ex vivo model that is largely resilient to arrhythmias",
says Jaimes. "Due to the nature of the design, it was
somewhat alarming that we found such significant effects. I predict that
electrophysiological disturbances will be more pronounced in models that more
closely resemble humans. These types of models should absolutely be studied."
Posnack adds: "And, importantly, our results may
incentivize the development and use of new products that are manufactured
The study was
funded by the National Institutes of Health, the Children's Research Institute,
and the Children's National Heart Institute, USA. NVIDIA Corporation, USA,
provided the graphics processing units, with partial support by the General Directorate
of Scientific Policy of the
- Plasticizer Interaction with the Heart - (https://www.ahajournals.org/doi/10.1161/CIRCEP.119.007294)