Ku Y, Saitoh M, Nishiyama H, Fujiwara S, Iwasaki T, Tominaga M, Maekawa Y, Ohyanagi H, Saitoh Y
First Department of Surgery, Kobe University School of Medicine, Japan.
Surgery. 1990 Mar;107(3):273-81.
The effect of a new extracorporeal system combining direct hemoperfusion (DHP) with venovenous bypass was evaluated in the elimination of anticancer drugs in hepatic artery infusion. Adriamycin (3 mg/kg) and mitomycin C (1 mg/kg) were given to mongrel dogs through the hepatic artery with three different durations of 1, 10, and 20 minutes. Plasma drug levels were determined at the inlet and outlet of DHP and right external jugular vein (systemic level). Blood flow through DHP averaged 200 ml/min. In dogs without DHP (group I; n = 4), systemic levels of adriamycin and mitomycin C increased rapidly with 1-minute infusion, reaching the peak values of 6.61 +/- 2.44 (mean +/- SD) and 2.20 +/- 1.05 micrograms/ml, respectively. With DHP under single venous bypass (group II; n = 5), the peak values were reduced to 1.25 +/- 1.02 and 0.79 +/- 0.52 microgram/ml. Moreover, the peak levels were markedly reduced by DHP under hepatic venous isolation (group III; n = 6), the values being 0.41 +/- 0.15 and 0.13 +/- 0.07 microgram/ml with 1-minute infusion. The drug-removal rates were improved substantially in group III compared with group II. The longer the duration of infusion, the higher the removal rates tended to be in group III. These results indicate that effective elimination of anticancer drugs can be accomplished by this system during intraarterial chemotherapy of the liver.
评估了一种将直接血液灌流(DHP)与静脉-静脉旁路相结合的新型体外系统在肝动脉灌注中消除抗癌药物的效果。通过肝动脉向杂种犬给予阿霉素(3mg/kg)和丝裂霉素C(1mg/kg),持续时间分为1、10和20分钟三种不同情况。在DHP的入口和出口以及右颈外静脉(全身水平)测定血浆药物水平。通过DHP的血流量平均为200ml/min。在未使用DHP的犬(I组;n = 4)中,1分钟输注后阿霉素和丝裂霉素C的全身水平迅速升高,分别达到峰值6.61±2.44(平均值±标准差)和2.20±1.05μg/ml。在单静脉旁路下使用DHP(II组;n = 5)时,峰值分别降至1.25±1.02和0.79±0.52μg/ml。此外,在肝静脉隔离下使用DHP(III组;n = 6)时,峰值水平明显降低,1分钟输注时的值分别为0.41±0.15和0.13±0.07μg/ml。与II组相比,III组的药物清除率有显著提高。在III组中,输注时间越长,清除率往往越高。这些结果表明,在肝脏动脉内化疗期间,该系统可有效消除抗癌药物。