Detecting Doxorubicin Cardiotoxicit in Rats Morphological and Hemodynamic Findings

Background. The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the "'In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings. Methods and Results. DOX was administered by intravenous injection to rats at a dose of 3 mg. kg' week` for 5 weeks. Three weeks after the final injection, an intravenous dose of "'In antimyosin, 740 kBq (20 pCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventzicles was more prominent in the DOX-treated rats than in control rats (p<0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p<0.001). As the severnty of the myocardial damage increased, there was a progressive increase in myocardial uptake. There