Cocaine-Induced Myocardial Ultrastructural Alterations and Cardiac Output Responses in Rats

Abstract

Cocaine use has been associated with profound functional and pathological myocardial responses in otherwise asymptomatic humans, yet a number of individuals appear to tolerate large doses of the drug. This study was designed to determine whether there is a relationship between the differential effects of cocaine administration on cardiovascular responses and on the development of cardiomyopathies in rats. After instrumentation for determination of cardiac output, conscious, freely moving rats were treated with cocaine (5 mg/kg) or saline intravenously twice daily for 14 days before removing the myocardium for analysis. Although most cardiovascular responses were similar, cocaine administration elicited consistent decreases in cardiac output in some rats, whereas others showed little change or an increase. While little change was evident at low magnification, electron microscopy revealed diffusely distributed myocardial lesions including locally dilated sarcoplasmic reticulum and myofibrillar derangement, early signs of mitochondrial alterations, and foci of myocardial fibrosis. The incidence of these alterations was greater in rats with a decrease in cardiac output. We also observed these lesions in a subset of rats treated with cocaine without cardiac output instrumentation. These data represent the first evidence that there is a relationship between cocaine-induced functional and pathological alterations and that rats, like humans, may be differentially sensitive to these effects.