Mortality and morbidity from cardiovascular toxicities of the recreational use of cocaine has become rampant in the Unites States. However, the prevalence of cardiovascular abnormalities in cocaine addicts is unknown, nor do we know the mechanism by which cocaine adversely affects the heart. The following protocol designs are based on our recent experience in studying cocaine-induced heart disease in chronic cocaine users. This was funded in part by the R01 DA05485 which show a significant cardiac abnormalities (i.e., abnormal ECGs, silent ischemic episodes). In addition, our pilot acute study revealed that at the 48 mg dose cocaine is sympathomimetic agent which abruptly increases dopamine, norepinephrine, epinephrine which are concordant with the increase in blood pressure and heart rate and serum cocaine concentration. We propose the study with the following objective. A prospective longitudinal study (Protocol 1) to determine the effects of chronic cocaine use on cardiac function, incidence of myocardial ischemia and other ischemic syndromes, and altered catecholamine states. A pilot study is also proposed to determine the acute pharmacologic effects of intravenous cocaine (48 mg) on coronary hemodynamics, the electrical activity of the heart and cardiac function at rest and during exercise. A double-blind dose-ranging study (Protocol 5) to determine the acute effects of intravenous cocaine on catecholamine homeostasis. The data from Protocols 2-5 will be crucial for the design of definitive studies to answer the following key questions: 1) What are the dose range and serum cocaine concentration that will compromise cardiac function and/or precipitate coronary vasoconstriction and/or spasm? 2) At what dose will the direct cardiovascular effects of cocaine become manifest? At what dose will cocaine effects on sympathetic activities become manifest? What are the roles of sympathetic blockade and calcium antagonist therapy in the treatment of cocaine toxicity?
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