Inhibition of platelet function in vivo or in vitro by organic nitrates.

Organic nitrates have been used to relieve angina since Brunton (l) first described their use in 1867. The assumption has been that nitrates decrease myocardial oxygen demand by reducing preload and afterload. In the last 20 years it has been established that unstable angina and possibly silent ischemia at rest are often due to platelet aggregates forming in stenosed coronary arteries. This platelet thrombus reduces coronary flow until the thrombus either disaggregates or embolizes distally, thereby restoring coronary flow. Several studies (2,3) have clearly demonstrated that aspirin reduces myocardial ischemic events in patients with unstable angina. There is considerable interest in being able to measure platelet function in vivo and in vitro to determine which substances-drugs or hormones-increase or decrease platelet activity. Until 1962 the only available means of measuring platelet function was clot retraction or bleeding time. In 1962 Born (4) developed the platelet aggregometer, a device in which light is passed through platelet-rich plasma placed in a clear glass cuvette. When a platelet agonist, such as collagen or adenosine diphosphate, is injected into the platelet-rich plasma, the platelets aggregate, making clumps of platelets that then fall to the bottom of the cuvette. As the platelets aggregate, the solution clears and the light transmittance increases. The degree to which the platelet-rich plasma solution clears is proportional to the functional activity of the platelets. Although this technique is useful, it takes approximately 90 min from the time blood is drawn from a patient or animal until the platelets can be studied. Thus, transient changes in platelet activity, such as those produced by cigarette smoking, can be missed (5). The present study. Stamler and Loscalzo (6) in this issue of the Journal carefully review the considerable evidence that suggests that part of the antianginal effect of nitro compounds given intravenously over time may well be due to the antiplatelet effect. The two main methods used to