Prenylamine inhibition of adriamycin-induced myocardiopathy.
Adriamycin (ADM) is an effective antineoplastic drug. However, ADM induces alterations in cardiac function which limit the safe dose which can be administered. As it was suggested that ADM-induced cardiomyopathy is related to a calcium mediated necrosis and/or an increase in lipid peroxidation, the cardioprotective potential of prenylamine (PNL) (a well known calcium antagonistic drug) was evaluated in rabbits given chronically large doses of ADM. Twenty five rabbits were allotted to 4 groups. Group I (PNL-ADM) was given 334 +/- 82 mg of PNL and 12.2 +/- 3.8 mg of ADM, group II (water-ADM) 14.4 +/- 4.6 of ADM, group III (PNL-saline) 280 +/- 91 mg of PNL and group IV (water-saline), same doses as ADM and PNL. Rabbits were sacrificed between 38 and 65 days after the beginning of the trial. In group I weight increased only 13% and in group II, 39% (p less than 0.01). Correlation coefficients were significant for variations of weight and ADM-doses (r = 0.875). In group II 8/10 rabbits showed post-treatment electrocardiographic changes, while group I changes were found in a lesser extent (5/10). Heart homogenates from ADM-treated rabbits showed an increased lipoperoxidation (74 +/- 5 cpm/mg protein X 10(-3) as compared with the control animals (58 +/- 6 cpm/mg protein X 10(-3) (p less than 0.05), while PNL treatment did not alter myocardial lipoperoxidation. Microscopically, myocardial fibers had from mild to severe hydropic vacuolization of sarcoplasm which led to progressive myocytolysis. Myocardial damage was lower in group I (ADM-PNL), 41.7 +/- 7.6 than in group II (water-ADM), 104 +/- 10.8 (p less than 0.05). It is suggested that ADM-peroxidation effects lead to lipoperoxidation with membrane damage and increase in Ca++ permeability, the latter being counteracted by PNL.
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000517:prevention & control; D004317:Doxorubicin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004562:Electrocardiography; D005260:Female; D008297:Male; D009206:Myocardium / Q000473:pathology; D011299:Prenylamine / Q000494:pharmacology*; D011817:Rabbits
D004317:Doxorubicin; D011299:Prenylamine