Redistribution of blood flow in experimental hepatic tumours with noradrenaline and propranolol

Abstract

Summary Noradrenaline induced changes in the distribution of blood flow in implanted tumour and normal liver tissue was measured using blood flow tracer microspheres. The ratio of embolised microspheres in tumour compared to normal tissue was determined before and after the intravenous infusion of noradrenaline, propranolol and a combination of the two drugs. The ratio was significantly decreased by noradrenaline alone but significantly increased when propranolol was added to the infusate. Propranolol had no effect on the ratio. The drug combination increased the tumour to normal ratio by approximately 69% and also doubled the proportion of microspheres entering the internal tumour circulation. This represents an enhanced relative blood supply to tumour and would provide a means of preferential carriage of blood borne cytotoxic agents to tumour tissue rather than normal tissue.

Randomised phase 2 trial of SIR‐Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer

“…The technique of SIRT, dosimetry, and preclinical studies have all been previously reported [2][3][4][5][6][7]. Injection of specific vasoactive drugs into the hepatic arterial circulation has been shown to greatly enhance tumour targeting with SIR-Spheres [8][9][10][11][12].…”

Selective internal radiation (SIR) therapy for treatment of liver metastases: Measurement of response rate

“…Furthermore, we have more recently described the use of several vasoactive agents that can preferentially redirect the microspheres into tumour tissue and away from normal hepatic parenchyma, further increasing the radiation dose delivered to the tumour metastases [9,10].…”

Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow

“…TNR increase has been shown to enhance the tumour uptake of small tracer molecules (Hemmingway et al, 1991) and the cytotoxic effect (Suzuki et al, 1981;Bloom et al, 1987). However, previous studies suggesting that vasoactive agents increase the TNR have measured blood flow with intermittent measuring techniques; these did not reveal either blood flow variations throughout vasoactive infusion (Burton, 1987;Carter et al, 1992) or the extent and direction of hepatic parenchymal and tumour blood flow change (Hafstrom et al, 1980;Burton et al, 1985). All the pressors tested in our study (but not the dilator CGRP) produced a significant maximal increase in the TNR because of a relatively larger pressor effect in liver parenchyma than in tumour ( Figure 5).…”