Science: Safer way to stop a coronary

 作者:毛腼     |      日期:2019-03-02 06:19:03
By BILL TARVER Coronary thrombosis may respond to a new version of an old treatment. Aspirin, which blocks one mechanism that causes blood clots, could be replaced by another drug that does the same job in a different and safer way. Blood platelets are the key to the formation of clots, or thrombi. Damage to fatty deposits (atheroma) or the endothelium lining the blood vessels changes the local serum chemistry, making platelets stick to the vessel surface. Platelets respond by releasing at least three important substances: thromboxane, adrenaline and serotonin. These in turn attract more platelets, which clump together and release more chemicals. The result is a positive feedback that develops into a thrombus and eventually a heart attack. Preventing a thrombosis depends on blocking the platelet cascade. Aspirin inhibits the thromboxane-induced sequence, but tends to cause internal bleeding, while blocking adrenaline would seriously disrupt the nervous system. So, what about blocking serotonin? Like adrenaline, serotonin (5-hydroxy-tryptamine, or 5HT) is an important neuro-transmitter with receptors in several locations: 5HT1 and 5HT3 receptors are found mainly in the brain, while 5HT2 receptors are found on platelets. Indeed, platelets are the richest source of serotonin outside the brain and secrete it in response to increased serotonin in the blood. Mark Noble of Charing Cross Hospital has spent several years experimentally blocking 5HT2 receptors in animals and people. In one early study, 61 patients with critical coronary artery disease were divided into two groups: 30 were treated with aspirin, and 31 with a 5HT2 blocker called ketanserin. After two years, seven people in the aspirin group had suffered a coronary thrombosis. Only one person in the ketanserin group suffered an attack (Coronary Artery Disease, vol 1, p 675). Ketanserin itself is not ideal as it has some unwanted side effects, but it is the only blocker currently licensed for treatment of people. Others have now been tested on animals, and a few are even better than ketanserin. According to research about to be published in the Quarterly Journal of Medicine, some will actually disperse a thrombus, which suggests that patients in the throes of a heart attack could be successfully treated, something not yet possible. Is there a danger that blocking the sero-tonin cascade will simply shift the impetus on to one of the thromboxane or adrenaline cascades? Results suggest not. 5HT2 antag-onists also reduce the effects of adrenaline and they don’t cause bleeding like aspirin. Assuming that licences are granted, Noble believes that all patients at risk can be treated with a 5HT2 antagonist. They can then wait in comparative security for a coronary bypass. The treatment should be quick,