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.