Methamphetamine induces an increase in cell size and reorganization of myofibrils in cultured adult rat cardiomyocytes

Abstract

To investigate the direct effects of methamphetamine (MAP) on cardiac lesions seen in MAP abusers, isolated adult rat ventricular cardiomyocytes (ARCs) were exposed to MAP (0.05–1.0 mM) in medium 199 containing 10% fetal calf serum. Isolated ARCs attached to laminin-coated substrata and began to spread into polygonal shapes with pseudopodia at day 6 in normal culture. However, the cell attachment and spreading were inhibited by exposure to MAP (0.5 and 1.0 mM) for the first 7 days in culture. On the other hand, exposure to MAP (0.05 and 0.1 mM) for 7 days after a 6-day period of normal culture, led to a larger cross surface area of cells with more abundant actin bundles compared to control cells (p < 0.05). This development of spreading area resembled that of norepinephrine-treated ARCs. In addition, immunoreactive atrial natriuretic peptide (ANP) granules developed and accumulated around the nuclear region of ARCs exposed to MAP and the number of ANP positive cells tended to increase in a dose-dependent manner. These results suggest that chronic exposure to a high concentration of MAP may directly inhibit development of ARCs in culture and that a continuous exposure to a low concentration of MAP may facilitate the development of cellular hypertrophy. Therefore, hypertrophied cardiomyocytes in MAP abusers may be provoked by multifactorial incidents of direct and indirect actions of MAP.