Effect of adriamycin on blood flow in renal tumour and normal renal tissue

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.