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.
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000
Katie Field, BBSRC (Jan 2016), £830,381
Alan Berry, Alex Breeze, Adam Nelson, BBSRC (Jan 2016), £479,490
Alan Berry, Wellcome Trust (Oct 2015), £752,365
Julie Aspden, MRC (Oct 2015), £633,020
Steve Sait, NERC (Oct 2015), £386,061
Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293
Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621
Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975
Dave Westhead, Leukaemia & Lymphoma Research
Leukaemia & Lymphoma Research (Sep 2015), £430,567
Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594
Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000
Eileen Ingham, John Fisher, EPSRC (Jul 2015), £1,458,439
Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019
Alex O'Neill, MRC (Jul 2015), £249,822
Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034
Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895
Helen Miller, ABNA Ltd (Jul 2015), £22,968
Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475
Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693
Elwyn Isaac, EU (Jun 2015), £238,915
Christine Foyer, BBSRC (Jun 2015), £160,401
Adrian Goldman, EU (Jun 2015), £116,331
David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378
Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672
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Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021
Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703
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Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103
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Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900
Andrew Tuplin, Royal Society (Mar 2015), £15,000
Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770
Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960
Stuart Egginton, BHF (Mar 2015), £272,979
Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066
Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171
Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000
Ian Hope, Marie-Anne Shaw, BBSRC (Jan 2015), £381,998
Paul Knox, BBSRC (Jan 2015), £5,000
Andrew Peel, BBSRC (Jan 2015), £359,077
Christine Foyer, BBSRC (Jan 2015), £408,334
Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521
Mike McPherson, Christoph Walti, DSTL Porton Down (Jan 2015), £625,125
Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015
Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937
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
Neil Ranson, BBSRC (Nov 2014), £355,253