title: Cocaine-induced cardiotoxicity in vitro.
abstract: A growing number of reports have related cocaine use with the onset of myocardial infarction in young otherwise healthy individuals. Although the cardiac effects of cocaine have traditionally been attributed to sympathomimetic stimulation, several studies have suggested that cocaine may be directly cardiotoxic. The purpose of this study was to evaluate the cardiotoxic effects of cocaine in an in vitro preparation devoid of sympathetic innervation. Primary cultures of rat cardiac muscle and non-muscle cells were prepared from hearts excised from 3-5-day-old Sprague-Dawley rats. Cultures were exposed to various cocaine concentrations (1 x 10(-7)-1 x 10(-3)m) for 1-24 hr. Beating activity, morphological status and lactate dehydrogenase (LDH) leakage were evaluated following cocaine exposure. A decrease in the beating activity of cultured muscle cells was observed 1 hr after exposure to the highest cocaine concentrations (1 x 10(-5)-1 x 10(-3)m) tested. Similar results were obtained 24 hr after exposure. Morphological alterations in muscle cells were evident only after exposure to the highest concentration (1 x 10(-3)m). Vacuoles appeared 1 hr after cocaine exposure and were replaced by dark granules within 24 hr. LDH release was significantly elevated in the muscle cell cultures exposed to 1 x 10(-3)m cocaine for 24 hr. The pattern of cocaine-induced morphological alterations and enzyme leakage was similar in non-muscle cells. These data suggest that cocaine induces direct toxic effects on both cardiac muscle and non-muscle cells maintained in an environment free of neuronal and hormonal influences.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, The University of Texas, Austin, TX 78712, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Welder
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Ramos
authors.forename: D
authors.initials: D
authors.lastname: Acosta