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.

Maternal methamphetamine administration during pregnancy influences on fetal rat heart development

“…In histopathological examinations, myocardial damage, such as eosinophilic changes, large and picnotic nuclei, hypertrophy and disarray of myofibers, was recognized in hearts from rats in the experimental group. These changes may arise from pharmacodynamic effects and/or direct toxicity of MAP (Matoba et al, 1985;He, 1995;He et al, 1996;Maeno et al, 2000). Although the MAP concentration (1.0 mg/kg) administered in our study was low (Cho, 1990;He et al, 1996), it was shown that MAP injured cardiomyocytes.…”

Cellular redox state protects acetaldehyde-induced alteration in cardiomyocyte function by modifying Ca2+ release from sarcoplasmic reticulum

“…After excision from male Wistar rat (7 wk old) under pentobarbital (50 mg/kg ip, Sigma, St Louis, MO) sedation, the heart was superfused with Krebs-Henseleit buffer solution composed of 118 mM NaCl, 2.6 mM KCl, 1.2 mM MgSO4, 1.2 mM KH2PO4, 11 mM glucose, and 25 mM NaHCO3 (pH 7.4), gassed with 95% O2 and 5% CO2. Cardiomyocytes were isolated by a collagenase digestion procedure described previously (13,20). Freshly isolated myocytes were suspended in Medium 199 (Sigma), containing 0.2% bovine serum albumin, and then seeded on laminin-coated glass coverslip bottom dishes and incubated at 37°C until used.…”

Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

“…However, since the effects of methamphetamine can include myocyte hypertrophy [10] and fibrosis [11,12], both relatively irreversible processes, it is likely that some patients will not recover left ventricular function with either appropriate medical therapy or abstinence from methamphetamine.…”