COCAETHYLENE TOXICITY IN RAT PRIMARY MYOCARDIAL-CELL CULTURES

Cocaethylene is a unique cocaine metabolite formed in the presence of ethanol by the liver. Neither acute nor chronic cardiotoxic effects of this metabolite have been investigated. The purpose of this study was to establish a time- and dose-dependent toxicity profile for cocaethy lene in primary myocardial cell cultures established from 3-5-day-old Sprague-Dawley rats. Alterations in lactate dehydrogenase (LDH) releas e, lysosomal neutral red (NR) retention, thiobarbituric acid-reactive substances (TBARS), morphology, and beating activity were evaluated af ter treatment of cultures with cocaethylene doses ranging from 1.0 X 1 0(-3) to 1.0 X 10(-9) M from 1 to 24 h. LDH release was significantly elevated after 24 h only with those cultures exposed to the highest do se of cocaethylene (1.0 x 10(-3) M). The highest dose of cocaethylene also significantly depressed NR retention. While all doses of cocaethy lene depressed contractile activity and altered cellular morphology by 24 h, there were no TBARS formed up to 15 h. Thus, both low and high doses of cocaethylene are injurious to the cellular integrity and cont ractility of myocardial cell cultures. Future studies are warranted to determine mechanisms of cocaethylene toxicity in this in vitro model of spontaneously contracting myocardial cells.