Compound in bear bile could prevent arrhythmia after heart attack
3 August 2011
A synthesised compound which is also found in bear bile could
help prevent disturbances in the heart’s normal rhythm, according to
research published today in the journal Hepatology by a team
from Imperial College London.
The compound, ursodeoxycholic acid (UDCA), alters the electrical
properties of myofibroblasts, which are muscle fibres present in
foetal hearts and in adult hearts following a heart attack.
UDCA is manufactured as a drug to decrease production of
cholesterol in the body and to dissolve gallstones. It is also
present in many traditional Chinese medicines made from bear bile.
The new study suggests it could also potentially treat abnormal
heart rhythm or arrhythmia, both in the fetus and in people who have
suffered a heart attack. Laboratory tests suggested that UDCA acts
on non-beating pathological heart cells called myofibroblasts, which
interfere with how electrical signals travel across the heart.
UDCA is already used to treat a condition called obstetric
cholestasis, which affects around one in 200 pregnant women in the
UK and is linked to a higher risk of arrhythmia and sudden death in
the fetus. UDCA lowers the levels of harmful bile acids which build
up in the mother’s blood in the disease and can pass into the infant
through the placenta.
The new study demonstrates for the first time that UDCA can
prevent arrhythmia by altering the electrical properties of
myofibroblasts. These cells are found in the fetal heart but
disappear shortly after birth. However, they reappear in patients
that have had a heart attack, when they are involved in laying down
scar tissue. The study found that these cells disrupt the
transmission of electrical signals that control the heart’s rhythm.
The study is the result of a long-term collaboration between two
Imperial research groups, headed by Dr Juila Gorelik, at the
National Heart and Lung Institute and Professor Catherine Williamson
at the Institute of Reproductive and Developmental Biology.
“These findings are exciting because the treatments we have now
are largely ineffective at preventing arrhythmia in patients who
develop an abnormal heart rhythm after a heart attack,” said Dr
Julia Gorelik, the study’s senior author.
“Our results from the lab suggest that UDCA could help the heart
muscle conduct electrical signals more normally. We’re hoping to set
up a clinical trial to test whether these results translate to
patients with heart failure.”
The researchers became interested in the role of myofibroblasts
after observing that they appear in the heart tissue in the second
and third trimesters of gestation, when sudden death of the infant
is most common in pregnancies affected by obstetric cholestasis.
The researchers grew myofibroblasts on top of heart muscle cells
in the laboratory to create a model for studying the fetal heart.
Then they used a number of specialised microscopic techniques to
study how the cells communicate to relay electrical signals.
Exposing the cells to high level of bile acid, as found in the
mother’s and fetal blood in obstetric cholestasis, caused the cells
to conduct electrical signals more slowly and increased the
likelihood of arrhythmia. This effect was not seen when there were
no myofibroblasts present among the heart muscle cells, as in the
healthy adult heart.
When the cells were exposed to bile acids and UDCA, it altered
the electrical properties of the myofibroblasts, and the electrical
signals propagated across the cell culture more regularly.
“Myofibroblasts affect the propagation of electrical signals that
co-ordinate the pumping function of the heart,” said Dr Michele
Miragoli, first author of the study. “Complications from obstetric
cholestasis occur most commonly in the last trimester of pregnancy,
when the density of myofibroblasts is highest in the fetal heart.
“Our study suggests that it is the appearance of myofibroblast
cells that make the fetus vulnerable to arrhythmia in obstetric
cholestasis. We think that targeting these cells could be an
important new approach for preventing abnormal heart rhythm, not
just in the fetus, but also in people who have had a heart attack.”
The study was funded by Action Medical Research, the Wellcome
Trust, the Swiss National Science Foundation, and the Imperial
Comprehensive Biomedical Research Centre, which was established by a
grant from the National Institute of Health Research.
M. Miragoli et al. A protective anti-arrhythmic role of
ursodeoxycholic acid in an in-vitro rat model of the cholestatic
fetal heart. Hepatology, 2011.