Better stents for the future

Dr Janet ChamberlainResearchers in the Department of Cardiovascular Science believe carbon monoxide could reduce complications arising from stent insertions. Dr Janet Chamberlain has £187,294 of British Heart Foundation funding over two years.

Every year, thousands of people in the UK receive a stent, or stents, to improve blood flow through a narrowed segment of a coronary artery called a stenosis. This stenosis is caused by a disease known as atherosclerosis. Stenting involves inserting a small mesh tube to widen narrowed coronary arteries. Generally, the procedure is effective in reducing symptoms of atherosclerosis and patients recover well.

However, scar tissue in the stented area can lead to re-narrowing of the blood vessel. BHF- funded researchers in the Dept of Cardiovascular Science believe that Carbon Monoxide Releasing Molecules (CORMs) may help to prevent this scarring or ‘restenosis’.

The most common treatment for symptomatic atherosclerosis is to put in a stent. This is a metal cage that opens up the artery, and keeps it open. Unfortunately, in the process of inserting the stent causes injury, or damage to the artery wall. This causes a wound healing reaction. Wounds heal by creating a scar that sometimes re-blocks the artery, so instead of being blocked by the disease of atherosclerosis, the artery is blocked by a scar. We call this re-blocking restenosis. It happens in around five per cent of patients with a stent, which doesn’t sound like a lot but it is several thousand people a year, when you consider the number of stents inserted each year.

Currently drug-eluting stents – polymer-coated stents that release drugs – are used to reduce the size of scar that forms, but they’re not perfect. Others have shown that Carbon Monoxide Releasing Molecules (CORMs) can reduce the risk of inflammation – which plays a major role in causing restenosis - and so we want to see whether they can reduce the risk of restenosis in stenting. The focus of this study is to establish the best type of CORM to use, and to find out how they are working.

The body produces carbon monoxide naturally. Previously, we thought it was just a by-product that we get rid of by breathing it out, however, people now recognise it has a positive biological effect in the body. Some have tried to increase this positive effect by giving more carbon monoxide to the body, giving it as an inhalable gas, but this has a lot of hazards because too much can lead to poisoning.

Restenosis ImageThe CORMs we’re working with are synthesised molecules. We’re using carbon monoxide bound to a chemical compound in the chemistry lab that releases carbon monoxide in the body, but they only release it in areas where conditions are right to allow the carbon monoxide to detach. Therefore, what happens is that the carbon monoxide is released in the body in the area where you want it as opposed to it being breathed into the lungs where it can cause toxic side effects.

We’re using two different types of CORM: CORM-3 and CORM-A1. One releases carbon monoxide very quickly, the other at a slower rate. Our aim is to find which CORM is the most effective and then, hopefully, in a project leading on from this look into whether we can put this onto a stent.