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

作者：Nazeyrollas P1, Prévost A, Baccard N, Manot L, Devillier P, Millart H.

网址:PMID: 9923553

求助者：天空的翅膀

• 求助时间：2015/6/27 21:37:36
• 求助状态：AB图书馆客服已找到全文，详情咨询在线客服qq 1257749646
• 文献摘要：

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.

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