Faculty of Biological Sciences

Research Bulletin

Anti-angina drug shows protective effects from carbon monoxide

6th August 2012

A University of Leeds led international research team has found that a common anti-angina drug could help protect the heart against carbon monoxide poisoning.

Animal studies have shown that the anti-angina drug ranolazine can significantly reduce the number of deaths from arrhythmias - irregular or abnormally paced heartbeats - that have been triggered by carbon monoxide.

The findings could have important implications for the development of a protective treatment for adults and children who have been exposed to toxic levels of the gas.

"When patients are admitted to hospital with carbon monoxide poisoning, the main problem doctors face is preventing damage to the body whilst the body slowly removes the chemical," said University of Leeds' Professor Chris Peers, who led the research. "We've shown that ranolazine can rapidly protect the heart and prevent the kind of cardiac events which threaten patients long after their exposure to the gas."

Carbon monoxide poisoning causes 1.6 million deaths worldwide every year. Many people who have been exposed to the gas develop cardiac arrhythmias, which if left untreated can lead to a fatal cardiac arrest.

Until now, however, the underlying biochemical mechanisms causing damage to the heart have not been fully understood, preventing the development of effective treatments.

Ranolazine, which is sold under the trade name Ranexa, was approved in 2006 in the US for the treatment of angina. The drug works by targeting a sodium channel in the heart - the same channel that can also induce irregular heartbeats.

Researchers at the University of Leeds examined the effect of ranolazine in single cardiac cells, to learn why carbon monoxide can trigger arrhythmias. They found that exposure to the gas caused a key membrane channel carrying sodium ions through the heart to stay open for longer. This in turn caused calcium to build up within cells, with the combined effect altering the heart's regular cycle.

Colleagues at the Université Montpellier 1 and Université de Avignon in France then trialled ranozaline on rats exposed to carbon monoxide, to test its protective effects. They found that the drug markedly reduced the chance of arrhythmia in the animals.

"Whilst the link between arrhythmias and carbon monoxide has been known for over 50 years, this is the first piece of research to explain the underlying process," said the Faculty of Biological Sciences' Professor Derek Steele, who co-authored the research. "At the molecular level, we have shown that the mechanism underlying this adverse effect of carbon monoxide is a rise in the level of nitric oxide within cells, which in turn alters the function of the sodium channel."

The findings may also help those living in built-up areas or whose work involves daily exposure to lower levels of carbon monoxide, such as firefighters, the researchers believe. A recent and extensive epidemiological study of nine million people in the US showed a clear link between environmental carbon monoxide exposure and hospitalisation due to cardiovascular complaints. As ranolazine is a daily medication for angina, the researchers suggest it may be suitable to protect patients from the harmful effects of chronic exposure, though human clinical trials will be required to confirm this.

"The next step will be to replicate these findings in human trials. As the drug has been clinically approved, roll out of this treatment could begin soon after we have these results," said Professor Peers.

Dr Hélène Wilson, Research Advisor at the British Heart Foundation (BHF), which co-funded the study, said: "This study is a good example of research being used to better understand the underlying causes of an abnormal heart rhythm and in this case it has uncovered the ability of an old drug to perform a new trick. Carbon monoxide poisoning is tragically common but hopefully these promising results can be replicated in people so that it saves lives in the future."

The research is funded by the BHF, Gilead Sciences, the Wellcome Trust and Fondation de France. The paper will be published in the American Journal of Respiratory and Critical Care Medicine.


Recent Grants

Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521

Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015

Bill Kunin, EU (Jan 2015), £157,490

John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000

Chris Hassall, Royal Society (Dec 2014), £14,500

Ryan Seipke, Royal Society (Nov 2014), £13,700

Alan Berry, Wellcome Trust (Oct 2014), £749,865

Ian Hope, Marie-Anne Shaw, BBSRC (Oct 2014), £396,565

Alison Ashcroft, Peter Stckley, Sheena Radford, Nic Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2014), £340,937

Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302

Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475

Paul Knox, EU (Oct 2014), £167,229

Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453

Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480

Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878

Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437

Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424

Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759

Andrew Peel, BBSRC (Sep 2014), £371,598

Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684

Lars Jeuken, BBSRC (Sep 2014), £313,463

Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763

Neil Ranson, BBSRC (Aug 2014), £355,253

Stuart Egginton, BHF (Aug 2014), £271,094

Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665

Peter Henderson, Leverhulme Trust (Aug 2014), £15,222

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960

John Trinick, BHF (Jun 2014), £222,614

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

Christine Foyer, Royal Society (May 2014), £24,000

Recent
News

New project to develop 'smart' pesticides

27th April 2015

University of Leeds researchers are playing a key role in an international collaboration to develop new, eco-friendly pesticides.


A bit of hot water can prevent the spread of invasive species

20th April 2015

When it comes to invasive species in the United Kingdom, a few ounces of hot water may be worth nearly £2 billion in annual management costs, according to a new study.


Parasite turns shrimp into voracious cannibals

18th March 2015

Parasites can play an important role in driving cannibalism, according to a new study.

 


New study on female fruit flies published by FBS Professor

17th March 2015

Female fruit flies may be more likely to reject the sperm of mates that are inferior, an international research team has found.


Uniting the women of science and engineering

10th March 2015

Three University of Leeds academics have been honoured with a Medical Research Council (MRC) Suffrage Award.


FBS Researchers volunteer to fight Ebola

17th February 2015

Four University of Leeds researchers have volunteered to fight the Ebola epidemic in Sierra Leone.


FBS Researchers discover viral code

4th February 2015

Researchers have cracked a code that governs infections by a major group of viruses including the common cold and polio.


Stroke damage mechanism identified

30th January 2015

FBS Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.


Impact
Stories

The Yorkshire Dales Environment Network is a partnership involved in the daily life and long term protection of the Yorkshire Dales.

Dr Utley has carried out research over a number of years to increase understanding of the issues faced by children with varying types of movement and co-ordination difficulties.

Research by Dr Keith Hamer on the foraging and breeding ecology has had impact in the understanding of interactions between seabirds and fisheries.

Badrilla is working with outstanding academic collaborators to develop new technologies for calibration of immunoassays.

All impact stories