Noradrenaline improves the tumour to normal blood flow ratio and drug delivery in a model of liver metastases.
Br J Surg
BACKGROUND: Vasopressors administered via the hepatic artery appear to increase drug delivery to colorectal liver metastases, but are limited by a short duration of action. This study measured their effect on blood flow and drug delivery during a prolonged infusion in a model of liver metastases. METHODS: In Hooded Lister rats with liver metastases, blood flow in tumour and adjacent normal liver was measured using laser Doppler flowmetry during a 30-min hepatic arterial infusion of endothelin 1, angiotensin II, vasopressin, N-nitro-L-arginine methyl ester (L-NAME), noradrenaline or saline (n = 6 per group). The same agents were co-administered with radiolabelled 5-fluorouracil (5-FU) (n = 6 per group) and uptake in the tumour and normal liver was measured. RESULTS: The mean(s.d.) duration of effect and resulting percentage changes in tumour to normal blood flow ratio of the vasopressors during this period were: noradrenaline, 2.9(0.4) min and 34(5) per cent (P < 0.05); angiotensin II, 4.2(0.2) min and 10(2) per cent (P < 0.05); vasopressin, 11.1(0.9) min and 7(2) per cent (P < 0.05); endothelin 1, 21.5(2.3) min and 14(5) per cent (P < 0.05); and L-NAME, 22.6(3.3) min and 2(1) per cent (P not significant). The mean(s.d.) uptake of radiolabelled 5-FU by the tumour in the groups studied was: saline, 5.1(3.2) x 10(5) c.p.m. per g tissue; angiotensin II, 5.1(1.4) x 10(5) c.p.m. per g; endothelin 1, 15.8(14.2) x 10(5) c.p.m. per g; L-NAME, 3.5(1.3) x 10(5) c.p.m. per g; and vasopressin, 6.8(3.5) x 10(5) c.p.m. per g. Significant improvements in 5-FU uptake only resulted from noradrenaline infusion (22.0(9.8) x 10(5) c.p.m. per g; P < 0.05). CONCLUSION: These findings suggest that hepatic arterially infused noradrenaline might be used to improve drug delivery to liver metastases.
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