The pathophysiology of cocaine cardiotoxicity

Abstract

Cocaine use is accompanied by a high risk of serious adverse effects involving the cardiovascular system. The basic cellular mechanisms of cocaine consist in [1] a potentiation of catecholamine effects by inhibition of the presynaptic uptake carrier [2] local anesthetic effects by the block of sodium-channels. Acute ischemic events can be induced by cocaine through coronary spasms in a situation of physiologic stress already accompanied by an enhanced myocardial oxygen demand. Procoagulant properties of cocaine may, moreover, favor coronary thrombosis formation and the development of myocardial infarction. Ischemia, reperfusion and the direct action of catecholamines on cardiocytes are accompanied by enhanced cytoplasmic calcium levels, inducing delayed after-potentials, repetitive action-potential generation and premature ventricular beats. Conduction velocity impairments caused by the local anesthetic effects of cocaine and inhomogeneous repolarization phenomena related to potassium channel inhibition may form a substrate for re-entrant circuits inducing ventricular fibrillation. Cocaine abuse may also cause degenerative and inflammatory alterations of the myocardium. Besides secondary ischemic changes, hypersensitivity-myocarditis and toxic cardiomyopathies that may be due to the cardiotoxic effects of catecholamines have been described in cocaine abusers. Moreover, persons using cocaine intravenously seem to be particularly endangered by bacterial endocarditis compared to the users of other intravenous drugs, for still unknown reasons.