Abstract

The effect of low (0.08 microU g-1 body wt min-1) and high (0.16 microU g-1 body wt min-1) rates of vasopressin infusion on blood flow to normal liver tissue and to liver metastases derived from azoxymethane induced colorectal carcinomas was studied in 36 male Wistar rats. Portal venous flow was measured by electromagnetic flowmetry and blood flow to normal and metastatic liver tissue by the clearance of xenon-133 injected directly into the liver parenchyma or metastasis. The low rate of vasopressin infusion decreased portal venous flow but increased blood flow to normal and metastatic liver tissue while at the higher rate of infusion these effects were reversed. Hepatic artery ligation (HAL) immediately following a low rate of vasopressin infusion abolished the observed increase in blood flow to both normal liver tissue and metastases. HAL immediately following the higher rate of vasopressin infusion further reduced blood flow to metastases but did not further alter blood flow to normal liver tissue. HAL prior to the infusion of the vasoactive drug significantly reduced blood flow to metastatic liver tissue, increased portal venous flow and was without effect on blood flow to normal liver tissue. Following HAL, blood flow to metastatic liver tissue was not further altered by either the low or high rates of vasopressin infusion. However, blood flow to normal liver tissue after HAL was reduced by a low rate of infusion of vasopressin and increased by the higher rate of infusion. The results of this study indicate that blood flow to normal or metastatic liver tissue can be increased or decreased by differential rates of infusion of vasopressin. These observations may have important implications in the treatment of liver metastases in man where different rates of vasopressin infusion may potentiate the effects of hepatic artery ligation or cytotoxic therapy.

Highlights

  • Study 1: The effect on portal haemodynamics of vasopressin infusion followed by hepatic artery ligation

  • Liver blood flow measured by the clearance of xenon-133 is lower in azoxymethane treated rats than in untreated rats (Mooney & Taylor, 1981)

  • Hepatic artery ligation has no effect on blood flow to the liver of azoxymethane treated rats (Mooney & Taylor, 1981)

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Summary

Methods

One hundred and eighty male Wistar rats (250 g) received s.c. injections of azoxymethane (10mg kg-1 body wt week -1) for 12 weeks. Forty-four weeks following the end of the azoxymethane treatment the animals were anaesthetised by an i.p. injection of sodium pentobarbitone and subjected to laparotomy. Multiple colonic tumours were found in all animals but liver metastases were only observed in 47. Rats with metastases in the liver were used in this study. Two studies were carried out differing from each other in the timing of hepatic artery ligation. Hepatic artery ligation was carried out after the infusion of vasopressin while in the second experiment the artery was ligated before the infusion of the hormone

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