Effects of seven anthracycline antibiotics on electrocardiogram and mitochondrial function of rat hearts.
Daunomycin, adriamycin and 5 semisynthetic anthracycline antibiotics inhibited oxygen consumption or ATP production of rat heart mitochondria in vitro. The no-effect levels varied depending on the substrate used and ranged from 1 nmole per mg mitochondrial protein. Mitochondrial functions were also studied in hearts of rats treated with repeated i.p. injections of the 7 antibiotics. Decrease in oxygen consumption without change in ATP production was observed with adriamycin and NSC-149584. Daunomycin, NSC-164011, NSC-143496 NSC-143114 affected primarily ATP production. The most potent compounds were daunomycin and adriamycin which damaged mitochondrial function at cummulative doses of approximately 10 mg/kg. ECGs were monitored in groups of equally treated rats. Cardiotoxicity manifested itself by progressive widening of the QRS complex often followed by the development of a S-wave trough. The most toxic compounds also induced intraventricular block, bradycardia and heart failure. The development of the ECG changes showed a good correlation with the impairment of mitochondrial function.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology* / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D004562:Electrocardiography; D004579:Electron Transport / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008931:Mitochondria, Muscle / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D000873:Anthracenes; D000900:Anti-Bacterial Agents; D000255:Adenosine Triphosphate