Carbon monoxide: a controlled heart therapy?

By Mike Nagle

- Last updated on GMT

Related tags: Blood, Hypertension

Several groups of scientists are developing compounds that slowly
release carbon monoxide directly into the bloodstream and that
could be used to treat diseases as diverse as high blood pressure,
heart disease and cancer.

Dr Ian Fairlamb and Dr Jason Lynam from the University of York have been awarded a £110,000 grant by the Leverhulme Trust for a three-year project to investigate using metal compounds to release carbon monoxide.

It may come as a surprise to learn that carbon monoxide, which is best known as a colourless, odourless highly toxic gas, can also used as an anti-inflammatory therapy.

Studies have shown it could reduce the risk of organ rejection after a transplant or even treat potentially fatal diseases such as pulmonary arterial hypertension (PAH). It could also prove to be a useful treatment for high blood pressure, heart disease and cancer.

However, inhaling the gas, even in small quantities is inherently dangerous. Carbon monoxide binds to and blocks haemoglobin, preventing it from carrying out its function as the body's oxygen carrier.

Even a small amount of carbon monoxide - whether the source from car fumes, smoking or even medicinal - can lead to oxygen starvation and, in higher concentrations, be fatal. Using metal compounds to deliver precise doses of carbon monoxide circumvents this risk.

Dr Lynam said: "We don't want to administer carbon monoxide in its normal toxic gaseous form; rather we want to develop molecules that will release it in a sort of slow trickle feed.

"We aim to make tuneable compounds which allow you to alter the rate at which carbon monoxide is released, which could be important in different bioapplications."

Dr Fairlamb added: "The research is very much in its infancy. We became involved because some of our organometallic compounds were showing potential to release carbon monoxide in a controlled manner. They degrade to give benign non-toxic products, which do not target immune response."

He continued: "You can use certain carbon monoxide molecules to elicit a whole range of biological effects. Carbon monoxide causes vasorelaxation and is produced naturally as a result of the breakdown of haemoglobin.

"This can be seen in the healing process of a bruise, where various colour changes indicate the degradation of haemoglobin and release of carbon monoxide. The slow release of carbon monoxide reduces blood pressure for someone who has angina, for instance."

This research builds on a study by Professor Brian Mann, University of Sheffield and Roberto Motterlini, Northwick Park Hospital, London.

Dr Mann's team have patented the use of metal carbonyls as a means of delivering carbon monoxide as a therapy. They have shown that the molecules can cause blood vessels to dilate, reduce hypertension, reduce transplant rejection, inhibit blood clotting and partially inhibit the production of nitric oxide, a molecule used by blood vessels to signal to surrounding muscles to relax, thereby dilating the artery and increasing blood flow.

Related topics: Preclinical Research

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