A PRIMARY CULTURE SYSTEM OF RAT HEART-DERIVED ENDOTHELIAL-CELLS FOR EVALUATING COCAINE-INDUCED VASCULAR INJURY

In clinical reports during the last der-ade, acute myocardial infarcti on has been reported in young, otherwise healthy, persons after cocain e use. These clinical reports suggest that recreational use of cocaine has adverse effects on the vasculature of the heart. The purpose of t his investigation was to evaluate cocaine-induced injury to heart-deri ved endothelial cells (ECs) obtained from adult male Sprague-Dawley ra ts. Alterations in lactate dehydrogenase release (LDH), lysosomal neut ral red retention (NR), and cell proliferation were evaluated after tr eatment of the ECs with cocaine doses ranging from 1 X 10(-7) to 1 X 1 0(-3) Mat 1, 4, and 24 h. Intracellular calcium levels were determined immediately after exposure to 1 X 10(-3) and 1 X 10(-2) M cocaine. LD H release, an index of cytoplasmic membrane injury, was significantly elevated after 24 h only with those ECs exposed to the highest dose of cocaine, 1 X 10(-3) M. In using NR as a score for lysosomal integrity and cell viability, no significant differences were observed for all treatment groups. However, all doses of cocaine suppressed EC prolifer ation by 10 days. Intracellular calcium levels were elevated on acute exposure to high concentrations of cocaine. These data suggest that bo th low and high doses of cocaine are injurious to ECs maintained in cu lture. Although the EC cultures remained viable, the integrity of cyto plasmic membrane was compromised with high doses of cocaine as demonst rated by LDH release and elevated intracellular calcium levels, wherea s all doses inhibited EC growth and proliferation.