Changes in hepatic haemodynamics in rats with overt liver tumour

Abstract

Summary Overt liver tumour was induced in Fisher rats by intraportal administration of 1.6 x 107 Walker carcinosarcoma cells. Control groups of rats received similar volumes of dead cells or saline intraportally. All animals were studied at 3 weeks when overt tumour was present. The Hepatic Perfusion Index (HPI) was significantly raised in rats with overt tumour compared to both groups of control animals. Portal flow and portal venous inflow were significantly reduced in the presence of overt tumour but hepatic arterial flow did not alter. These observations suggest that the alteration in the HPI in the presence of overt tumour results from an alteration in portal venous flow and inflow even though the blood supply to the tumour is principally derived from the hepatic artery. The changes in hepatic haemodynamics in the presence of tumour were accompanied by a reduction in portal pressure, an increase in splanchnic vascular resistance and an increase in the degree of arteriovenous shunting through the liver. Portal vascular resistance was unchanged. These findings indicate that the presence of overt hepatic tumour results in gross derangements of hepatic blood flow. These changes must be taken into consideration when attempting to potentiate the delivery of cytotoxic drugs to hepatic tumour by manipulation of hepatic haemodynamics.The hepatic perfusion index (HPI), that is the ratio of hepatic arterial to total hepatic blood flow determined by dynamic scintigraphy is elevated in the presence of overt tumour in man (Leveson et al., 1983). Previous studies have suggested that the blood supply to overt liver tumour is derived principally from the hepatic artery (Taylor et al., 1979 Radionuclide studies Ten rats injected intraportally with either viable Walker cells or the same number of dead Walker cells and ten rats receiving saline were anaesthetised with intraperitoneal sodium pentobarbitone and the right common carotid artery exposed through a midline cervical incision. A 10 cm length 2FG polyethylene cannula was introduced into the carotid artery via an arteriotomy. The cannula was screened into position in the left ventricle using a Siemens Siremobile (Siemens Ltd., Sunbury-on-Thames, UK) image intensifier such that its tip was approximately 1 mm below the aortic valve. Adequate expulsion of a small bolus of injectate by the left ventricle was confirmed by injecting 0.1 ml Sodium Meglumine via the cannula. The rats were then placed under an N.E.8900 Gamma camera (Nuclear Enterprises Ltd., Edinburgh, UK) with a 1 cm pinhole collimator linked to a PDP DEK computer (Digital Equipment Corporation, Maynard, Massachusetts, USA). 9'9Tc sulphur colloid (0.04 ml) with an activity of 80 MBq was injected rapidly as a bolus into the left ventricle using a 50 tl High Pressure Liquid Chromatography syringe. Images were acquired at three frames per second and stored on hard disc for subsequent analysis. A compositie image of the first five frames of each study was constructed and regions of interest (ROI) were drawn arqund t...

Nature of Doppler Perfusion Index Changes in Patients With Colorectal Cancer Liver Metastases

“…13 Also, portal vasoconstriction was noted in rats with experimental cholangiosarcoma (Walker carcinosarcoma). 12 However, no systemic humoral vasoactive agent responsible for hemodynamic changes in patients with colorectal liver metastases has been identified to date.…”

“…10 Conversely, a significant reduction of portal venous flow was recorded in another experimental model, with no alterations in arterial hepatic flow. 12 Therefore, the main hemodynamic alteration in patients with colorectal cancer liver metastases (an increase in arterial hepatic flow or a decrease in portal venous flow) is still not clearly defined. Total body plasma volume was found to be significantly related to body surface area, and blood flow through various vessels is routinely expressed in relative proportions to body surface area.…”

“…It has been postulated that these changes in hepatic blood flow are the result of increased hepatic arterial blood flow, 7,10 whereas other studies suggested a predominant role of decreased portal venous flow. 11,12 Such conclusions have been based on the assessment of a predominant change in blood flow through the common hepatic artery or portal vein.…”

Arteriovenous Sphingosine-1-Phosphate Differences Across Selected Organs of the Rat

“…Sphingolipid concentration in mixed portal and arterial plasma was calculated using weighted averages of sphingolipid levels determined in samples taken from these blood vessels, assuming that 80% of total liver blood flow was supplied by the portal vein [27, 28]. …”

Contrast‐Enhanced Doppler Perfusion Index

“…t is known from experimental animal studies [1][2][3] and clinical patient studies [4][5][6][7][8][9] that the presence of even microscopic liver metastases is associated with changes in hepatic hemodynamics. The mechanism is not clear, although changes have been shown to originate from the early nonvascular phase of the metastases 3 and may be mediated by circulating vasoactive agents as a response to neoplastic growth.…”