Illicit use of cocaine has reached epidemic proportions in most major cities in the USA and at least 4 to 5 million Americans use it regularly. Cocaine has been clinically described to cause myocardial ischemia and infarction, coronary thrombosis and sudden cardiac death. We have observed in a preliminary study on """"""""Pathobiologic determinants of atherosclerosis in youth"""""""" that the thoracic and abdominal aorta from young cocaine associated death victims (19 patients) had increased sudanophilia in the absence of well known risk factors compared to non-cocaine associated trauma related deaths (17 pts). Also, in another study, severe coronary atherosclerosis (>75% cross-sectional area luminal narrowing) occurred in 5 of 6 patients who died with cocaine associated thrombosis (mean age 29 + 6 years). The atherosclerotic plaques were rich in macrophages and smooth muscle cells. Acute and chronic inflammatory cells (T and B cells) were seen within intima, media, and adventitia suggestive of an immunologically mediated injury. Therefore, we propose to expand these observations to determine the role of cocaine in atherogenesis. In the aortas and coronary arteries of young (15-44 years) cocaine and noncocaine-associated death victims we will: 1. determine the role of cocaine and other drugs of abuse in the initiation and progression of atherosclerosis and their relationship to the usual risk factors. 2. determine the presence and extent of macrophages; B and T lymphocytes; mast cells and smooth muscle cells utilizing immunohistochemical techniques and computerized image processing and their relationship to cocaine and other risk factors. 3. subtype T cells into CD4 (inducer) and CD8 (cytotoxic), and natural killer lymphocytes, and determine if these may be present in different proportions in cocaine and noncocaine users. 4. determine the presence and role of cytokines (interleukin-1, tumor necrosis factor and interferon gamma) in atherosclerosis and if these are present in increased amounts in cocaine users. These studies will help us confirm our preliminary observations of accelerated atherogenesis in cocaine user, establish the relationship to other risk factors of atherogenesis, and clarify a mechanism of initiation and progression of atherosclerosis.
