How nitrate could bring an end to heartache

There are hopes of major improvements in the care of angina patients following the successful investigation of a newly developed nitrate medicine by researchers at King's College School of Medicine in London.

More than 12,000 patients in the United Kingdom each year undergo balloon angioplasty, a widening of the coronary arteries to relieve angina, which is caused by a shortage of blood supply to the heart. A catheter with an uninflated balloon at its tip is inserted into an artery in the groin, and inflated at the area where the arteries narrow, widening the diseased area and restoring blood flow.

The procedure is highly effective, but in some cases patients suffer complications with blood clots which can cause an acute blockage, and around a third of patients find the coronary artery narrows again.

Platelets, the small white blood cells which begin the process of blood clotting, are thought to be implicated both in the formation of clots and in the longer term process of renarrowing arteries. Aspirin is used to reduce clot formation, but does not prevent renarrowing.

The King's College team, lead by John Martin, British Heart Foundation professor of cardiovascular science, studied 13 patients undergoing angioplasty, all of whom received standard medication to inhibit clotting. But ten minutes before the angioplasty, six of them were also given nitrate medicine which inhibited the platelet activity.

In the seven patients who formed the control group, there was increased platelet activity, which was at its height five minutes after angioplasty. This is the first time that this activity has been demonstrated in humans.

Professor Martin and his team, writing in the Lancet, suggest that the nitrate medicine causes nitric oxide to be released by the platelets, which stops them sticking either together or to the wall of the artery and forming clots.

The effect of nitric oxide on the whole body is to relax blood vessels and cause a drop in blood pressure. But the new medicine seems to deliver nitric oxide locally to platelets which are becoming sticky, and not to blood vessels, avoiding side effects of the blood pressure drop, headache and nausea.

Professor Martin said the discovery by Salvador Moncada in 1987 of nitric oxide as a messenger in the body was one of the most important biological discoveries of the decade. "Now we are seeing for the first time that the blood-clotting mechanism is activated during angioplasty and we have evidence that this might be counteracted without side effects."

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