Could scorpion toxin improve the outcome of heart bypass surgery?
27 October 2010
A coronary artery bypass graft (CABG) is performed on a patient when coronary arteries become narrowed or blocked. Typically a leg vein is taken and attached to the aorta to bypass the blockage. Despite an increase in less invasive procedures, some 25 000 CABGs are carried out in the UK each year, with 45 per cent of vein bypasses failing within seven years.
When a leg vein is grafted onto the heart, it has to cope with different circulatory pressures. Neointimal hyperplasia is the growth of new cells allowing the vein to strengthen and adapt to its new environment, but this is also the most common cause of CABG failure.
Problems arise when the growth of new cells becomes too prolific - causing blockages on the inside of the vessel, which can lead to a failure of the graft. Recent research funded by the Wellcome Trust, the British Heart Foundation and the Medical Research Council shows that venom from the Central American bark scorpion (Centruroides margaritatus) may prove to be an effective weapon against neointimal hyperplasia.
One of the scorpion's toxins, margatoxin, has been shown to be at least 100 times more potent at suppressing neointimal hyperplasia than any known compound. The toxin works by partially inhibiting a specific potassium ion channel. This channel is a pore in the cell membrane that opens and closes in response to electrical signals, indirectly enhancing delivery of an intracellular messenger.
By inhibiting this channel, margatoxin is able to prevent excessive cell proliferation and will potentially increase the long-term success of CABG. Whille a sting from the Central Amerian bark scorpion is not fatal to humans, the margatoxin is hugely potent and very effective.
"It's staggeringly potent. We're talking about needing very few molecules in order to obtain an effect," explains Professor David Beech, who lead the research.
"There were a number of good blockers of this ion channel available to screen. Several compounds are developed from plants, but margatoxin was the most potent of all these compounds by a significant margin," he says.
Professor Beech suggests that, in the future, margatoxin may be sprayed directly onto the leg vein, right before it is grafted onto the heart, as is common with other drugs.
Image: Central American bark scorpion; squamatologist on Flickr
Reference
Cheong et al. Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers. Cardiovasc Res 2010.