2000 Fiscal Year Final Research Report Summary
Studies on the mechanism of cardiotoxicity of methamphetamine using isolated cardiomyocytes.
| Project/Area Number |
11670423
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Nagoya City University |
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Principal Investigator |
MAENO Yoshitaka Nagoya City University, Medical School, Assistant Professor, 医学部, 講師 (00145749)
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| Co-Investigator(Kenkyū-buntansha) |
IWASA Mineo Nagoya City University, Medical School, Associate Professor, 医学部, 助教授 (00021452)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Methamphetamine / Isolated cardiomyocyte / Cellular hypertrophy / ANP / Cardiotoxicity |
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| Research Abstract |
Pathological alterations occasionally found in the myocardium of methamphetamine (MA) abusers include cellular hypertrophy, atrophy, and disarrangement of myofibrils, myolysis and fibrosis. These cardiac alterations have been considered to be due to an indirect action of MA via catecholamines released by MA administration. However, the direct effects of MA on cardiomyocytes are not clear. The aim of this study is to investigate isolated adult rat ventricular cardiomyocytes (ARCs) whether MA directly influences the development of cardiac lesions such as seen in MA abusers. Freshly isolated ARCs were cultured in medium 199 containing 10% fetal calf serum (FCS) and were chronically exposed to various concentrations of MA (0.05-1.0 mM) for 7 days. The exposure to 0.5 and 1.0 mM MA for the first 7 days in culture inhibited the cell attachment to substrata and the cell spreading which were seen in the morphological transition of control ARCs in a long-term culture including FCS.On the other
… More
hand, after a 6-day period of FCS-supplemental culture, ARCs undergo redifferentiation (Rediff), namely cellular spreading and growth. When ARCs were exposed to 0.05 and 0.1 mM MA during Rediff, the largest cross surface area of a cell, which was measured using an image analytical system after labeling for F-actin with rhodamine conjugated phalloidin, was significantly larger than that of untreated cells (p<0.05). Furthermore, immunoreactive atrial natriuretic peptide (ANP) granules developed and accumulated around the nuclear region of ARCs exposed to MA and the number of the positive cells tended to increase as compared with control cells. On exposure to 0.5 mM MA, the development of cell size was not observed and either disappearance of immunoreactive microtubular structure or loosely and irregularly oriented actin fibers existed in the cytoplasm of ARCs. Therefore, several cardiac lesions seen in MA abusers may be provoked by multifactorial incidents of direct and indirect actions of MA. Less
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