Hideaki Fukunaga

Effects of tolbutamide on cultured heart cells of mice

To investigate the direct effects of tolbutamide on the myocardium, we studied the ultrastructure, direct effects of tolbutamide on the myocardium, we studied the ultrastructure, beating rhythm, cytotoxicity determining the 51Cr release from damaged cells and the 45Ca activity in the cultured heart cells of mice. After 48 h of cultivation, tolbutamide was added to give a final concentration of 0.37, 0.93, 1.85, and 3.7 nM. The addition of high dose of tolbutamide (greater than 1 mM) to the culture medium produced irregular beating after 1 min and cessation of beating after 20 h. The cultured heart cells incubated with control solution or low concentrations of tolbutamide (less than 1 mM) showed little change in the beating rhythm and frequency. Cytotoxicity of tolbutamide on the cultured heart cells was observed only in high concentrations (greater than 1 mM): the 51Cr release index was 23% at 1.85 mM and 40% at 3.7 mM. On electron microscopy, the heart cells cultured with high concentration of tolbutamide (greater than 1 mM) showed electron-dense bodies in the mitochondria and shortened Z-Z intervals. However, these ultrastructural alterations were not observed in the cultured heart cells incubated with low concentration of tolbutamide (less than 1 mM). The 45Ca activity of cultured heart cells, after the incubation for 24 h in medium containing 45Ca, was significantly increased only with high concentrations of tolbutamide (greater than 1 mM). We conclude that tolbutamide in dose of less than 1 mM had no cytotoxicity and had little effect on the beating rhythm, ultrastructure and intracellular calcium concentration of the cultured heart cells of mice.

Chlorpromazine-induced cardiomyopathy in rats

SummaryWe studied the chronic effects of chlorpromazine (CPZ) on the myocardium of rats using light and electron microscopy. Wistar strain rats were divided into two groups and given either normal saline or CPZ intraperitoneally at a dose of 5 mg/kg body weight/day for 30 consecutive days. Myocardial degeneration, atrophic muscle fiber, and myocardial fibrosis were observed by light microscopy in all CPZ-treated rats. Ultrastructural alterations of the myocardium were also found in all CPZ-treated rats. They consisted of contracted myofibers, mitochondriosis, degenerated mitochondria, dilated sarcoplasmic reticulum, and increased collagen fibers. However, no abnormal histologic or ultrastructural changes were observed in the normal saline-treated rats. We therefore conclude that a chronic administration of a sedative dose of CPZ causes myocardial damage in rats.

Diltiazem prevents the damage to cultured aortic smooth muscle cells induced by hyperlipidemic serum

Diltiazem, a calcium antagonist, significantly reduced the increased45Ca uptake and the number of dead cells in cultured aortic smooth muscle cells induced by hyperlipidemic serum.

Cultured heart cells from the spontaneously diabetic KK mouse

SummaryIn order to clarify the mechanism of myocardial changes in KK mice, cultured heart cells from both normal and spontaneously diabetic KK mice were studied by electron microscopy, photoelectric recording, and45Ca activity. Compared with cultured heart cells from normal mice, those from KK mice showed a decrease in beating frequency and ceased beating more rapidly. The rhythm of the beating cells from KK mice became irregular, while that of the heart cells from normal mice was not changed significantly over a period of 10 days. Electron micrographs of cultured heart cells from KK mice showed an increased number of mitochondria, an intricate arrangement of myofibrils, poorly formed Z bands, and a lipidlike substance. The45Ca activity of heart cells from KK mice, after incubation for 24 h in a medium containing45Ca, was increased compared with heart cells from normal mice.Based on these findings, we conclude that ultrastructural alterations exist in cultured heart cells from KK mice and we suggest that an increase of intracellular Ca might play an important role in the pathogenesis.