'Bear bile' chemical studied for irregular hearts

Behind the Headlines

Wednesday August 3 2011

Bear bile does contain UDCA, but the chemical is usually man-made

“Bear bile could help prevent arrhythmia in heart attack sufferers,” reported the Daily Mail.

This headline is based on a laboratory study investigating the effects of bile acid on the electrical signals of foetal heart cells from rats. The study found that the addition of a specific bile acid called ursodeoxycholic acid (UDCA) to a layer of rat foetal heart cells protected them against impaired electrical signals – a characteristic of irregular heart rhythm.

The study provides an important new insight into a potential therapy for heart arrhythmia at the cellular level. However, this study on rat cells in the laboratory cannot show whether UDCA will be effective at reducing arrhythmia in either adults or children.

Further research is needed to see whether the protective effects of UDCA seen in this laboratory study will translate into similar effects on human heart cells and if there are any safety issues. Although UDCA can be derived from bear bile, the drug is more commonly produced synthetically, as was the case in this study.

 

Where did the story come from?

The study was carried out by researchers from Imperial College London. Funding was provided by Action Medical Research, the Wellcome Trust, the British Heart Foundation, the Biomedical Research Centre at Imperial College Healthcare NHS Trust and the Swiss National Science Foundation.

The study was published in the peer-reviewed science journal Hepatology. It was generally covered accurately in the news.

 

What kind of research was this?

The researchers say that previous studies suggests that cholestasis (a condition of the digestive system) is a common disorder in women in their third trimester of pregnancy. They say there is a range of associated foetal complications, and that pregnant women with cholestasis are at a higher risk of their unborn baby having irregular heart rhythms (arrhythmia), low oxygen or being miscarried.

This research aimed to investigate the biological link between cholestasis in pregnancy and arrhythmia in the foetus. Cholestasis is where bile, which aids digestion, cannot flow from where it is made in the liver to where it is needed in the digestive system. The excess bile builds up and can cause damage, potentially to the unborn baby. Heart arrhythmia is a condition where there is abnormal electrical activity in the heart. Some arrhythmias can result in sudden death, whereas others may be much less serious.

The researchers aimed to explore the reasons behind this association at a cellular level. In this laboratory study, they examined the effect of different bile acids on rat heart tissue.

 

What did the research involve?

The researchers tested the action of the bile acid on two types of heart cell derived from rats. They used a non-beating type of heart cell called myofibroblasts, as well as cardiomyocytes, which contract and cause the beating movement of the heart.

The researchers used human heart samples of foetuses at 9-26 weeks to detect the presence of myofibroblasts at different stages of the foetal heart development. Healthy adult heart tissue does not usually have myofibroblasts, so the presence of these was used to detect damage to the heart during foetal development.

The researchers then set up laboratory models of the maternal heart and foetal heart using rat cells and exposed these tissues to different levels of a specific bile acid called taurocholoate to mimic the effect of cholestasis. They measured the effect of the different levels of bile acid on the electrical signals being transmitted in the heart cells.

They then used a second bile acid (ursodeoxycholic acid, or UDCA) to see how this affected the electrical signal characteristics of the cells, both alone and in combination with taurocholate. Although UDCA can be derived from the bile of bears, the drug is more commonly produced synthetically, as was the case in this study.

 

What were the basic results?

Results using human cells

The researchers found that MFBs temporarily appeared in human foetal heart tissue around the second and third trimesters, reaching a peak at 15 weeks. This is the same period of pregnancy that cholestasis-related sudden foetal death is most common. These cells were not detected after birth.

Results using rat cells

Temporary (10-20 minutes) addition of the bile acid taurocholate to the foetal heart cells markedly decreased the speed at which the electrical signal spread across the heart tissue, from 19.8cm per second to 9.2cm per second. This effect was also seen when taurocholate was applied for longer (12-16 hours).

In the maternal heart model the addition of taurocholate showed no effect.

Exposure of the maternal heart cells to the other bile acid (UDCA) had no effect. However, in foetal heart cells treated with UDCA the speed of the electrical signals increased significantly compared to cells that were not treated with UDCA.

When UDCA was used alongside taurocholate in foetal cells, there was no decrease in electrical signal speed that would otherwise have been caused by taurocholate. When UDCA was withdrawn the electrical signal speed again decreased, suggesting that the presence of UDCA was key to maintaining the normal speed of the electrical signal. The effect of UDCA was found to be greatest in the myofibroblast heart cells.

 

How did the researchers interpret the results?

The authors conclude that their study shows that myofibroblasts temporarily appear in the heart during foetal development and that taurocholate (at concentrations comparable with cholestasis during pregnancy) induces signs of arrhythmia in the foetus. They also conclude that UDCA protects against the effects of this condition by acting on the myofibroblast cells.

They go on to report that the prevention of these arrhythmias by UDCA “represents a new therapeutic approach for cardiac arrhythmia” at the cellular level.

 

Conclusion

This study provides important new information about the effect of UDCA on the electrical signalling patterns of rat foetal heart cells. However, it has some limitations.

This study was mainly conducted in the laboratory on rat heart cells that were used to mimic human foetal and maternal heart cells. Some experiments on human cells were carried out, but none that directly studied human heart cells within the body. Therefore the effect of UDCA on human heart cells within the body is unknown and may be different from the effect seen in the rat cells under the artificial laboratory conditions.

The study provides an important insight into a potential therapeutic approach for heart arrhythmia at the cellular level. However, there is often a substantial delay between the identification of a therapeutic target in the laboratory and the production of a drug or treatment that can be used in humans. Future experiments on human heart cells within the body will provide further insight into the effect of UDCA on heart cells and its safety.

At present, its potential to protect developing foetuses from arrhythmia in women who suffer from cholestasis during pregnancy remains unknown. Further research would also need to establish whether UDCA can be used in adults or children to potentially reduce arrhythmia or the risks of sudden death.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Bear bile could help to prevent arrhythmia in heart attack sufferersDaily Mail, August 3 2011

Bear chemical brings heart hope. BBC News, August 3 2011

Links to the science

Miragoli M, Sheikh SH, Kadir A, et al. A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart. Hepatology 2011, article first published online: August 1

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