Effect of regional angiotensin II infusion on the relationship between tumour blood flow and fluorouracil uptake in a liver metastasis animal model.
The aim of this study was to assess the relationship between tumour:liver blood flow and 5-fluorouracil (5-FU) uptake ratios in a hypovascular liver metastasis animal model, and examine whether they were similarly affected by a 5 min infusion of angiotension II via the hepatic artery. Tumour:liver blood flow ratio was measured using the isotope tracer 64Copper (II)-pyruvaldehyde bis(n-4 methyl thiosemicarbazone, and 5-FU was tritiated. There was a wide variation in tumour:liver blood flow and 5-FU uptake ratios which could only partly be explained by between animal variation, and was not related either to individual tumour size or overall tumour burden within the liver. There was a close correlation (r = 0.957, P < 0.0001) between tumour:liver blood flow and 5-FU uptake ratios. Angiotensin II infusion significantly increased tumour:liver blood flow (nested analysis of variance, P= 0.05) but not 5-FU uptake (P = 0.29) ratios. There was a poor correlation (r = 0.51, P = 0.13) between tumour:liver blood flow and 5-FU uptake ratios with angiotensin II infusion. Thus, despite an increased 5-FU blood concentration arising from angiotensin-induced reduction in blood flow at constant 5-FU infusion dose, tumour:liver 5-FU uptake ratio did not increase as expected, and there ceased to be a significant correlation between tumour:liver blood flow and 5-FU uptake ratios. We conclude that the vasoactive changes within the hypovascular tumour circulation produced by a 5 min angiotensin II infusion did not significantly increase tumour 5-FU uptake.
Department of Surgery, Charing Cross and Westminister Medical School, London, U.K.
M J
MJ
Dworkin
J
J
Zweit
P
P
Carnochan
B
B
Deehan
T G
TG
Allen-Mersh
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D001783:Blood Flow Velocity / Q000187:drug effects*; D005472:Fluorouracil / Q000493:pharmacokinetics*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism* / Q000556:secondary; D008297:Male; D011849:Radioactive Tracers; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D011849:Radioactive Tracers; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005472:Fluorouracil