Tvete S, Hope A, Elsayed E A, Clausen G
Eur J Cancer Clin Oncol. 1982 Jun;18(6):565-71. doi: 10.1016/0277-5379(82)90226-7.
The effect of adriamycin (Adm) on local blood flow was simultaneously measured in neoplastic tumour, diameter 3-5 mm, and intact tissue in rat kidneys using the H2 gas washout technique. Constant rate i.v. infusion of Adm, 0.3-6 mg/kg/min for 3-15 min, increased mean arterial blood pressure (AP) by 20%, a maximum already obtained at the lower infusion rate, without affecting heart rate. Control tumour flow averaged 0.9 (0.4-1.1) ml/min/g. Flow was inversely related to Adm infusion rate in both tissues, but tumour flow tended to be relatively less affected. In another series of experiments total renal blood flow (RBF) was recorded electromagnetically during constant rate infusion of Adm into the renal blood stream, 0.03-3 mg/kg/min for 3-20 min. AP increased and RBF decreased during the first 2 min of infusion, whereafter steady levels were maintained. Both parameters returned to control levels within 4 min after completed infusion, irrespective of infusion rate and duration. High i.a. infusion rates, 2-3 mg/kg/min, almost stopped RBF but gave no further AP increase (max at approximately 0.5 mg/kg/min), indicating a direct constrictor effect on renal vessels. On the other hand, the AP response persisted when renal circulation was excluded, suggesting a general pressor response evoked by Adm. A 60% RBF reduction was obtained by 1 mg/kg/min i.a. as compared to 4-6 mg/kg/min i.v. infusions. This indicates that a several times higher Adm concentration was maintained in renal blood during i.a. infusion. Taken together with the recovery time, this observation also suggests a post-infusion blood clearance of Adm with an initial half-time of about 2 min or less. This was confirmed in additional experiments where [3H]-labelled Adm was determined in timed blood samples.
采用氢气洗脱技术,同时测量了直径3 - 5毫米的大鼠肾脏肿瘤组织及完整组织中阿霉素(Adm)对局部血流的影响。以0.3 - 6毫克/千克/分钟的恒定速率静脉输注Adm 3 - 15分钟,平均动脉血压(AP)升高了20%,在较低输注速率时就已达到最大值,且不影响心率。对照肿瘤血流平均为0.9(0.4 - 1.1)毫升/分钟/克。两种组织中的血流均与Adm输注速率呈负相关,但肿瘤血流受影响的程度相对较小。在另一系列实验中,以0.03 - 3毫克/千克/分钟的恒定速率向肾血流中输注Adm 3 - 20分钟,期间用电磁法记录总肾血流量(RBF)。输注的前2分钟内AP升高,RBF降低,之后维持稳定水平。输注结束后4分钟内,无论输注速率和持续时间如何,两个参数均恢复至对照水平。高腹腔内输注速率(2 - 3毫克/千克/分钟)几乎使RBF停止,但未使AP进一步升高(最大值约为0.5毫克/千克/分钟),表明对肾血管有直接的收缩作用。另一方面,排除肾循环时AP反应仍持续存在,提示Adm引发了全身性升压反应。腹腔内输注1毫克/千克/分钟时RBF降低60%,而静脉输注4 - 6毫克/千克/分钟时降低程度相同。这表明腹腔内输注期间肾血中Adm浓度维持在数倍于静脉输注的水平。结合恢复时间来看,该观察结果还提示输注后Adm的血液清除存在,初始半衰期约为2分钟或更短。在额外实验中,通过定时采集血样测定[³H]标记的Adm,证实了这一点。