The candidate's major career research goals are to explore the pathophysiologic mechanisms by which psychological variables affect the etiology and outcomes in coronary heart disease. The major emphasis in this area will be hemostatic factors, particularly the role of platelets in acute coronary thrombosis. There is substantial evidence that platelets play a central role in acute coronary events, and there is also evidence that psychological stress can induce increased platelet activation, most likely through epinephrine stimulation. Much of the evidence to date in this area has relied on indices of platelet secretion for measurement of platelet activation, which are indirect and may not completely reflect activation induced by epinephrine. Recent developments in platelet physiology have led to the development of direct measures of activation, including membrane receptor markers that define activation (glycoprotein IIb/IIIa). We intend to use these measures initially in two studies: (1) activation induced by a laboratory stressor (speech) and a naturalistic stressor (dissertation defense) in 40 healthy graduate students; and (2) activation as it occurs during atherosclerotic plaque rupture, subsequent thrombosis, and after thrombolytic therapy in patients admitted to the coronary care unit. In both studies, catecholamine levels will be measured and related to platelet activation. Studies that follow will use these measures as well. In addition, an in vitro model using a perfusion chamber (badimon chamber) will be used to examine the effects of stress on platelet deposition on injured stenotic blood vessels. The candidate has access to multiple resources to accomplish these studies, including psychophysiology, flow cytometry, and perfusion laboratories.
