Amifostine improves hemodynamic parameters in doxorubicin-pretreated rabbits.

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.