Effects of amifostine on perfused isolated rat heart and on acute doxorubicin-induced cardiotoxicity

Cancer Chemother Pharmacol. 1999;43(3):227-32. doi: 10.1007/s002800050888.


Purpose: To determine the effects of amifostine on an isolated perfused rat-heart model and its protective activity with regard to cardiotoxic doxorubicin perfusion.

Methods: Langendorff constant-pressure isolated rat-heart preparations were used to analyze the effects of the drugs during a 40-min period of perfusion after a 20-min stabilization interval. The first study was conducted with amifostine alone (controls and 10(-6), 10(-5), and 10(-4) M amifostine; n=6 in each group). The second study was conducted with amifostine and doxorubicin (controls, 2.5 x 10(-5) M doxorubicin, 2.5 x 10(-5) M doxorubicin and 10(-5) M amifostine, and 2.5 x 10(-5) M doxorubicin and 10(-4) M amifostine; n=4 in each group).

Results: Amifostine had no significant effect on hemodynamic parameters at 10(-6), 10(-5), and 10(-4) M concentrations. However. amifostine increased the coronary flow expressed as a percentage+/-SEM of the baseline flow as follows: 82+/-4% for controls, 95+/-6% for 10(-6) M amifostine, (P=0.13), 111+/-4% for 10(-5) M amifostine (P < 0.01), and 104+/-3% for 10(-6) M amifostine (P < 0.01). When we commenced an amifostine perfusion 20 min in advance of and then during a 40-min perfusion with doxorubicin, at a cardiotoxic concentration of 2.5 x 10(-5) M the left ventricular pressures (LVDP, expressed as percentages +/-SEM of the baseline LVDP before doxorubicin) were 55+/-3% for the doxorubicin controls, 68+/-2% for doxorubicin with 10(-5) M amifostine (P=0.05), and 80+/-3% for doxorubicin with 10(-4) M amifostine (P < 0.01). Whether this protective effect might be related to the known free-radical-scavenging activity of amifostine remains to be determined.

Conclusion: On a Langendorff-type model of rat heart, 10(-5) and 10(-4) M amifostine alone induced a coronary dilation and, when associated with a cardiotoxic concentration of 2.5 x 10(-5) M doxorubicin, 10(-5) and 10(-4) M amifostine displayed a cardioprotective effect.

MeSH terms

  • Amifostine / pharmacology*
  • Animals
  • Antibiotics, Antineoplastic / antagonists & inhibitors*
  • Antibiotics, Antineoplastic / toxicity
  • Coronary Circulation / drug effects
  • Creatine Kinase / metabolism
  • Doxorubicin / antagonists & inhibitors*
  • Doxorubicin / toxicity
  • Heart / drug effects*
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects
  • Myocardium / enzymology
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Wistar


  • Antibiotics, Antineoplastic
  • Doxorubicin
  • Creatine Kinase
  • Amifostine