A quantitative analysis of leptomeric fibrils in an adriamycin/carnitine chronic mouse model

A quantitative ultrastructural analysis of leptomeres in cardiac muscle was performed using an adriamycin/carnitine chronic mouse model. Five animals from each of the following four groups were sacrificed for evaluation by electron microscopy: the control group received saline injections only; the carnitine group received carnitine orally; the adriamycin group received a chronic dose of adriamycin (10 mg/kg over 4 weeks); the adriamycin/carnitine group received both the adriamycin and carnitine dosage regimens. The leptomeres were quantitated using a double-blind method. The total number of leptomeres were scored for 20 random low-power electron micrographs from each of 5 animals within each group. The adriamycin group contained 3 of the 4 lowest leptomere scores. The relationships between myofibrillar disruption (MD) and the number of leptomeres found in an intramyofibrillar location(IML) were then determined for each of the four groups using linear regression analysis. In the control group, increased MD was associated with a decrease in the number of IML. In the carnitine group, increased MD was associated with an increase in IML. In the adriamycin group, no significant change in the number of IML occurred with increasing levels of MD. The adriamycin/carnitine group was similar to the control group. It was concluded from this study that 1) a relationship exists between MD and the number of IML in normal murine cardiac muscle; 2) carnitine produces an inverse effect on this normal relationship; 3) adriamycin disturbs the normal relationship between IML and MD; and 4) the administration of carnitine to adriamycin-treated animals restored the normal relationship. The physiological significance of the leptomere to the cardiac cell is then discussed.