The Study of the Changes of Myocardial Histology and Left Ventricular Function according to the Total Doses of Doxorubicin in Rabbits

Choi, Jeong Hwa; Park, Hee Ju; Lim, Young Tak; Kim, Bong Seon; Huh, Eun Young

Abstract

PURPOSE: We'd like to evaluate the relationship between the degree of cardiac damage and that of cardiac function according to the total injected dose of doxorubicin.
METHODS
12 rabbits(body weight : 2.0-3.2 kg) were used and 30 mg/m2/week of doxorubicin hydrochloride was injected intravenously. The cardiac function was checked under anesthesia, after which the thorax was opened and cardiac samples were evaluated with light and electron microscopics.
RESULTS
Regardless of total injected dose of doxorubicin, there was no difference between the general appearance, sizes and thickness of both atria and ventricles of doxorubicin injected rabbits and those of normal control. The rabbits with total cumulative dose <180 mg/m2 showed no differences with the rabbits of normal control in the cardiac histology. The rabbits with cumulative doses of 210 mg/m2 had an increased number of vacuoles in the interspaces of the myofibrils and glucogen granules in myocytes. The rabbits with the cumulative dose of 240 mg/m2 had focal necrosis and degeneration of myocytes with fibrous cells infiltration. The rabbits with cumulative doses of 300 mg/m2 demonstrated severe and diffuse degenerations with markedly decreased numbers of myocytes and increased intracellular vacuoles. All the rabbits with total cumulative doses <240 mg/m2 showed no difference in the aortic pressure, left ventricular(LV) maximal dP/dt and left ventricular end diastolic pressure(LVEDP) compared to normal control. The rabbit with total cumulative doses of 300 mg/m2 showed no difference in the aortic pressure and LV maximal dP/ dt, but revealed significantly elevated LVEDP compared to normal control.
CONCLUSION
These results showed doxorubicin induced cardiotoxicity is dose related and may be certain at total cumulative dose >200 mg/m2, although cardiac function is normal.