Despite cocaine's history of medical and recreational use, and despite its wide use as a tool in studying adrenergic synaptic function, there is a paucity of information concerning its cardiovascular effects. Cocaine, which blocks neuronal uptake of norepinephrine and also exerts local anesthetic actions, should have complex cardiovascular effects, but to date the only well documented actions in man or conscious animals are increases in heart rate and blood pressure. The effects of cocaine on the cardiovascular system during stress have not been studied. We propose to examine the cardiovascular effects of acute and chronic cocaine treatment in anesthetized dogs as well as in trained conscious dogs. In addition, we plan to study the effects of acute and chronic cocaine treatment on cardiovascular function during stress resulting from exercise and myocardial infarction. Initial studies will define the dose-response relationships for cocaine on cardiovascular parameters in order to determine a dose of cocaine which produces effects on blood pressure and heart rate in the dog comparable to those desceibed in humans after intravenous administration of moderate-to-high abuse doses (16-32 mg), so that subsequent chronic studies can be performed in a dose range of cocaine that produces cardiovascular actions similar to those observed in man. We will also examine the influence of cocaine on cardiac beta adrenergic receptors, since recent work in the central nervous system indicated that acute and chronic cocaine treatment stimulates up-regulation of beta receptors. If this occurs in the heart, it may be of profound importance during periods of stress when sympatho-adrenal activity is elevated. Finally, the effects of acute and chronic cocaine treatment on cardiovascular function during exercise will be studied to determine whether or not cocaine alters the cardiovascular and/or temperature regulatory responses to this stress. Similarly, the effects of acute and chronic cocaine treatment on the myocardial response to coronary artery occlusion will be studied to determine whether cocaine treatment alters the time course or intensity of arrhythmias and/or the extent of myocardial necrosis resulting from ischemia. These studies should provide answers to questions of whether or not acute or chronic cocaine use during exercise places additional demands on cardiovascular function and whether or not use of cocaine at the time of a heart attack or its subsequent use by individuals after recovery from a heart attack may increase morbidity and/or mortality.
