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.


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Peter Stockley, Wellcome Trust (Apr 2014), £251,019

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Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237

Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350

Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874

Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Ronaldo Ichyama, Samit Chakrabarty, International Spinal Research Trust (Jan 2014), £304,600

Brendan Davies, BBSRC/Bayer Crop Science SA-NV (Jan 2014), £470,053

Adrian Goldman, Steve Baldwin, Stephen Muench, Thomas Edwards, Arwen Pearson , BBSRC (Jan 2014), £467,103

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Elwyn Isaac, EU (Jan 2014), £179,445

Dave Westhead, Leukaemia & Lymphoma Research (Jan 2014), £105,937

John Barr, Thomas Edwards, MRC (Dec 2013), £469,505

Alex O'Neill, MRC (Dec 2013), £349,017

Darren Tomlinson, Yorkshire Cancer Research (Nov 2013), £142,334

Nikita Gamper, MRC (Nov 2013), £336,563

Keith Hamer, Alison Dunn, NERC (Nov 2013), £47,233

Alan Berry, Wellcome Trust (Oct 2013), £749,365

Urwin, Howard Atkinson, BBSRC (Oct 2013), £360,508

Eileen Ingham, Stacey-Paul Wilshaw, NHS R&D (Oct 2013), £356,623

Sheena Radford, BBSRC (Oct 2013), £329,906

Nigel Hooper, Alzheimer's Research (Oct 2013), £327,075

Eileen Ingham, EPSRC (Oct 2013), £276,751

David Beech, BHF (Oct 2013), £109,974

Mark Harris, Medical Research Foundation (Oct 2013), £34,455

James Dachtler, Royal Society (Oct 2013), £15,000

Ade Whitehouse, Teresa Rosenbaum Golden Charitable Trust (Oct 2013), £10,000

Jurgen Denecke, BBSRC (Sep 2013), £382,093

Andy Cuming, EU (Sep 2013), £257,714

Paul Knox, BBSRC (Sep 2013), £411,948

Vas Ponnambalam, Leverhulme Trust (Sep 2013), £245,031

Peter Meyer, EU (Sep 2013), £242,166

Dave Rowlands, Nic Stonehouse, EU (Sep 2013), £202,556

Derek Steele, BHF (Sep 2013), £103,629

Joan Boyes, NC3Rs (Sep 2013), £90,000

Peter Stockley, Royal Society (Sep 2013), £11,400

Darren Tomlinson, Leverhulme Trust (Sep 2013), £5,645

Nic Stonehouse, Dave Rowlands, BBSRC (Aug 2013), £574,906

Eileen Ingham, Wellcome Trust (Aug 2013), £191,470

Adrian Goldman, Royal Society (Aug 2013), £75,000

Mike McPherson, Wellcome Trust (Aug 2013), £40,000

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