title: Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II.
abstract: 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 (AI) 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 micrograms AII over 90 s. 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 AII 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 AII 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 AII and other vasoconstrictors to enhance targeting precision.
authors.affiliation: University Department of Surgery, Glasgow Royal Infirmary, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Hemingway
authors.forename: W J
authors.initials: WJ
authors.lastname: Angerson
authors.forename: J H
authors.initials: JH
authors.lastname: Anderson
authors.forename: J A
authors.initials: JA
authors.lastname: Goldberg
authors.forename: C S
authors.initials: CS
authors.lastname: McArdle
authors.forename: T G
authors.initials: TG
authors.lastname: Cooke
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000556:secondary; D008991:Monitoring, Physiologic; D012039:Regional Blood Flow / Q000187:drug effects; D013599:Systole
chemical_list: D000804:Angiotensin II