Platelet activation in clinical coronary artery disease and spasm

Current concepts of atherogenesis, based on animal models, suggest a role for platelets in the development of atherosclerotic lesions, possibly through the release of alpha granule constituents. Platelets may also contribute to the development of vascular spasm through thromboxane A 2 production. Platelet activation in the coronary circulation in patients with coronary artery disease (CAD) should occur if these hypotheses apply clinically. We measured aortic and coronary sinus plasma levels of the platelet alpha granule constituent β-thromboglobulin (B-TG) and thromboxane B 2 (TX B 2) by radioimmunoassay in 15 patients with severe atherosclerotic CAD, seven patients with angiographically normal coronaries, and five patients undergoing evaluation for coronary artery spasm (CAS). Compared with the controls, CAD patients had significantly greater transmyocardial release of B-TG (11.1 ± 8.1 ng/ml, mean ± SEM vs 62.5 ± 17.2, p < 0.05 by rank sum test); TX B 2 gradients showed a similar trend but the difference was not statistically significant (−0.08 ± 0.03 ng/ml vs 0.22 ± 0.02, 0.05 < p < 0.10). Three of the five patients studied developed CAS which was associated with acute elevation in coronary sinus TX B 2; the two non-CAS patients with drug provocation had undetectable coronary sinus TX B 2. We conclude that abnormal platelet activation takes place in the coronary circulation of CAD patients, and that production of acute myocardial ischemia by CAS occurs with increased coronary sinus TX B 2.