Fetal lead toxicity.

Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (Al) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 ltg AII over 90s. Six patients with isolated small metastases (<5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of All infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following All infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of All and other vasoconstrictors to enhance targeting precision. Regional administration of chemotherapeutic agents provides a means of increasing drug delivery to liver metastases (Kemeny et al., 1987), which derive their blood supply almost entirely from the hepatic artery (Ackerman et al., 1969). It has been suggested that the use of vasoconstrictors would further increase tumour exposure to regionally-delivered drugs (Suzuki et al., 1981). On the grounds that tumour blood vessels are deficient in both smooth muscle and adrenergic receptors, and are believed to lack the capacity to respond normally to vasoactive agents (Mattsson et al., 1977). Selective constriction of vessels supplying normal liver would be expected to divert a higher proportion of hepatic arterial flow, together with any arterially-infused drug to tumour. We have previously demonstrated that angiotensin II increases delivery of a regionally administered marker to liver tumour (Hemingway et al., 1991), and increases tumour uptake of radiolabelled albumen microspheres in patients with colorectal liver metastases (Goldberg et …