Angiotensin alteration of drug uptake in an experimental model of hepatic metastases.
To evaluate the use of angiotensin-II (A-II) as a means of improving results with intra-arterial infusions of hepatic tumors, 32 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine [( 3H]FUDR) was administered via peripheral ear vein in 9 control rabbits (iv), via the hepatic artery in 12 rabbits (HA), and following a constant infusion of A-II in the remaining 11 rabbits (HA/A-II). Biopsies of tumor and normal hepatic parenchyma were taken and tissue levels of FUDR measured. Hepatic artery infusions, both with and without A-II, resulted in a significantly greater tumor uptake of FUDR than the iv infusions (P less than 0.001). More importantly, the tumor/liver ratio of FUDR uptake was significantly greater in the HA/A-II group (3.40) than that in the HA without A-II (0.98) group (P less than 0.001). This difference is due to the decreased FUDR uptake by normal hepatic parenchyma in rabbits undergoing A-II infusion; tumor drug uptake is similar for both groups. We conclude that the addition of angiotensin II to hepatic artery infusional chemotherapy significantly improves the tumor/liver ratio of drug uptake in this experimental model of hepatic metastases.
Trezona
T
T
Harbor-UCLA Medical Center, Department of Surgery Torrance 90502.
Butler
J A
JA
Vargas
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005467:Floxuridine / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D011817:Rabbits; D014407:Tumor Cells, Cultured
D005467:Floxuridine; D000804:Angiotensin II