EFFECT OF CONTINUOUS REGIONAL VASOACTIVE AGENT INFUSION ON LIVER METASTASIS BLOOD-FLOW

Regionally administered vasopressors might increase tumour chemotherap y uptake by differentially constricting normal and tumour blood vessel s, leading to a selective increase in blood flow to the tumour. In thi s study, we compared the effects of the vasopressors angiotensin II, v asopressin and endothelin I and the vasodilator calcitonin gene-relate d peptide (CGRP) by continuously measuring liver parenchymal and tumou r blood flow during a 30-min regional vasoactive infusion in a rat HSN liver metastasis model. Vasopressin and angiotensin II produced a vas oconstriction that decreased despite continued infusion, while endothe lin I infusion led to prolonged vasoconstriction with a more gradual o nset. CGRP infusion resulted in increased vessel conductance but a red uction in blood flow due to systemic hypotension. The tumour to normal flow ratio (TNR) was transiently increased during infusion of all pre ssors, but only endothelin I produced sufficient change to result in a rise in average TNR throughout presser infusion. Continuous liver and tumour blood flow measurement throughout vasoactive infusion demonstr ated that the extent and the duration of blood flow change varied with the agents assessed. No vasoactive agent increased tumour blood flow, but endothelin I had the most suitable vasoactive properties for enha ncing tumour uptake of continuously infused chemotherapy.