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Effects of seven anthracyclin antibiotics on electrocardiogram and mitochondrial function of rat hearts

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Abstract

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 to 800 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 funciton at cumultive doses of approximately 10mg/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 mitochondiral function.

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This paper is dedicated to Professor A. Töndury Zurich, at the occassion of this 70th birthday.

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Bachmann, E., Weber, E. & Zbinden, G. Effects of seven anthracyclin antibiotics on electrocardiogram and mitochondrial function of rat hearts. Agents and Actions 5, 383–393 (1975). https://doi.org/10.1007/BF02205248

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Keywords

  • Oxygen
  • Heart Failure
  • Oxygen Consumption
  • Mitochondrial Function
  • Anthracycline