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.
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Lisa Collins, BBSRC (Feb 2018), £49,950
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Alison Baker, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
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Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
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Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
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Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
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Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
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Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
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Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
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Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576