Abstract
Regional chemotherapy for colorectal liver metastases has not demonstrated a convincing survival benefit over systemic chemotherapy. This may be due to poor delivery of chemotherapeutic drugs to hypovascular liver tumour. Since vasoactive agents may influence hepatic blood flow this study investigated the effects of systemic and regional vasoconstrictors on the delivery of a regionally delivered marker in an experimental model of liver tumour. Systemic administration of angiotensin II caused a significant retention of marker in normal liver, but not in tumour compared to controls. Regional delivery of angiotensin II and phenylephrine caused significantly greater retention of marker in tumour than liver with an overall 4-fold increased retention of marker one minute after its injection. Ninety minutes after injection there was still significant retention of marker compared to control animals. Regional delivery of hepatic artery vasoconstrictors increase delivery of marker and may increase delivery of chemotherapeutic drug to liver tumour.
Highlights
Systemic administration of angiotensin II caused a significant retention of marker in normal liver, but not in tumour compared to controls
We have developed a model of hypovascular liver tumour in the rat, and a technique using a radiolabelled marker of similar molecular size to cytotoxic drug to determine whether manipulation of intrahepatic blood flow by vasoactive agent increases its delivery and retention by liver tumour relative to normal liver tissue (Cooke & Chang, 1990; Hemingway et al, 1989a)
The tumour:liver ratio in rats infused with angiotensin II was 0.6:1 compared to 1.5:1 in controls
Summary
The aim of this study was to investigate the effects of regional and systemic administration of angiotensin II and phenylephrine on the distribution of regionally delivered marker to normal liver tissue and tumour in rats
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