Effects of nitrendipine on cocaine-induced toxicity evaluated in primary myocardial cell cultures.
Currently, there is no uniform treatment for abnormal cardiac events precipitated by cocaine use. However, clinical strategies include use of calcium channel antagonists for cardiovascular emergencies. In experimental situations using rats, simultaneous administration of nitrendipine (NIT) with cocaine to the whole animal (1.46 x 10(-3) mg/kg/min of NIT; 2 mg/kg/min of cocaine) and isolated retrograde perfused hearts (Langendorff; 1 x 10(-7) M NIT; 1 x 10(-7) to 1 x 10(-4) M cocaine) normalized cocaine-induced abnormalities in heart rhythm and provided protection from acute cocaine-induced morphological lesions. Using similar concentrations of NIT and cocaine, the purpose of this study was to evaluate the direct cardiac cellular effects of NIT on cocaine-induced alterations in beating activity, morphology, and lactate dehydrogenase (LDH) release in a controlled in vitro system of primary myocardial cell cultures. Cultures were established from hearts of 3-5-day-old Sprague-Dawley rats. After the cells had been maintained in culture for 4 days, evaluation of drug effects were made with exposure to 1 x 10(-3) and 1 x 10(-5) M cocaine alone and combinations of these two concentrations of cocaine with simultaneous exposure to 1 x 10(-7) M NIT for 1 to 24 h. Those cells exposed to 1 x 10(-5) M cocaine alone maintained some beating activity after 1, 4, and 24 h. Beating activity was significantly depressed after treatment with 1 x 10(-3) M cocaine alone and with both combinations of cocaine and NIT. Morphological integrity was maintained in all treatment groups for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
R B
RB
Melchert
J A
JA
Eselin
J F
JF
O'Dell
A A
AA
Welder
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009568:Nitrendipine; D007770:L-Lactate Dehydrogenase; D003042:Cocaine