Amifostine improves hemodynamic parameters in doxorubicin-pretreated rabbits

Pharmacol Rep. Nov-Dec 2006;58(6):966-72.

Abstract

Amifostine reduces nephrotoxicity and myelotoxicity of alkylating agents. Little is known about its role in preventing cardiotoxicity. We studied if amifostine could affect the hemodynamic parameters in doxorubicin-pretreated rabbits. The animals were divided into six groups consisting of 6 rabbits each. Group 1--doxorubicin iv 2 mg/kg of body weight 4 times every 14 days (cumulative dose 8 mg/kg); group 2--a dose of doxorubicin was 3 mg/kg (cumulative dose 12 mg/kg); groups 3 and 4--amifostine iv 30 mg/kg 15 min prior to doxorubicin 2 and 3 mg/kg, respectively, groups 5 and 6--amifostine- and physiological saline-treated controls. Two-three weeks after the last dose the animals were anesthetized and cardiac index (CI) i.e. cardiac output/body weight, and total peripheral resistance (TPR) were calculated using the method of human I(125) albumin dilution. Mean CI was 71.4 +/- 40.5 ml/min/kg in group 2, 135.8 +/- 41.2 in group 5 (p < 0.001), and 116.4 +/- 47.8 in group 6 (p < 0.001), TPR was 4.7 +/- 3.3 kPa x s/l, 1.1 +/- 1.2 (p < 0.001), and 1.9 +/- 1.1 (p < 0.001), respectively. In group 4, CI was 135.4 +/- 33.2, and TPR was 1.1 +/- 0.6. The differences in CI and TPR between groups 2 and 4 were statistically significant (p < 0.001). In conclusion, pretreatment with doxorubicin at the total dose of 12 mg/kg significantly reduced CI and increased TPR. Amifostine improved CI and TPR in doxorubicin-pretreated rabbits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amifostine / pharmacology*
  • Animals
  • Cardiac Output / drug effects*
  • Doxorubicin / toxicity*
  • Female
  • Male
  • Rabbits
  • Vascular Resistance / drug effects*

Substances

  • Doxorubicin
  • Amifostine