Women's health research at NIEHS.

The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 106 HSN sarcoma cells. At 20 days, hepatic arterial blood flow was measured using the reference microsphere technique. Animals then randomly received 50 1l hepatic arterial saline or albumin microspheres (40jim, 20mgml-'). Hepatic arterial blood flow measurements were then repeated at 5 min. After 5 min, animals were killed and tissues were weighed and counted in a gamma well counter. There were no significant differences between the hepatic blood flow measurements recorded before and after the control hepatic arterial saline infusion. However, regional albumin microspheres produced a significant reduction in tumour and normal liver blood flow and an 80% reduction in mean T/N blood flow ratio. Regional albumin microspheres were delivered to tumour in greater proportions (mean T/N ratio 3.89, SE 0.49) than would be expected from baseline hepatic arterial blood flow (mean T/N ratio 1.28, SE 0.22. P = 0.006). There was no correlation between T/N for baseline blood flow and albumin microsphere distribution. Drug-loaded or radioactive microspheres may be administered via the hepatic artery for the treatment of liver metastases (Herba et al., 1988; McArdle et al., 1988). It has generally been assumed that such embolic particles are distributed to tumour and normal liver in proportion to their respective arterial blood flows. However, recent work in a rat liver tumour model has shown that the distribution of albumin microspheres to tumour relative to normal liver (T/N ratio) varies significantly with both microsphere diameter and concentration ; larger, more concentrated microspheres tend to produce higher T/N ratios than those obtained with dilute suspensions of small microspheres (Anderson et al., 1991). The reasons underlying these observed differences in T/N ratios and their relationship to the distribution of hepatic arterial blood flow are not understood. Furthermore, the effects of regional microsphere delivery on hepatic arterial blood flow require elucidation. Enhancement of the T/N ratio may be achieved with drug-induced modification of liver blood flow. Vasoactive agents, such as angiotensin II, induce vasoconstriction in normal liver whilst tumour vessels, which lack smooth muscle, remain dilated. Therefore microspheres administered after angiotensin II are targeted to tumour (Goldberg et al., 1991). It is not known whether the optimum T/N ratio achieved with large, concentrated microspheres can be potentiated …