Methamphetamine-induced toxicity in cultured adult rat cardiomyocytes

Abstract

In an attempt to differentiate the direct effects of methamphetamine from the indirect sympathomimetic effects on the myocardium, primary culture of adult rat myocytes were established under serum-free conditions, and they were exposed to methamphetamine (1 x 10(-5) and 1 x 10(-3) M) for 1 to 24 h in the presence and absence of 1 x 10(-6) M propranolol. Cardiotoxicity was evaluated by light and ultramicroscopy, release of cytoplasmic enzymes (Lactate dehydrogenase: LDH and Creatine phosphokinase: CPK) and change in membrane permeability (Trypan blue stain). After 24 h methamphetamine treatment, light microscopy exhibited cellular granulation and swelling, myocyte hypercontraction, broken cellular membrane and cellular destruction. After the same time, electron microscopy revealed swelling and irregular mitochondria with disrupted cristaes, clump of sarcomeres with nearly complete loss of organized contractile elements, injury of intracellular membrane system and dissolution of myofibrils. These injurious features were more severe with the 1 x 10(-3) M methamphetamine. Propranolol (1 x 10(-6) M), a beta-adrenergic antagonist, failed to protect the myocytes against methamphetamine-induced cell injury. Release of LDH from methamphetamine (1 x 10(-5) and 1 x 10(-3) M)-treated myocytes increased significantly only after 24 h, while significant CPK release was observed in 1 x 10(-3) M methamphetamine-treated myocytes at 4 h. These findings suggest that methamphetamine exerts direct toxic effects on adult rat myocytes rather than indirect ones via receptors, although further experiments on more concentrations of propranolol are required.