Ashraf, Shahzad; (1996) Ultrastructure and perivascular innervation of blood vessels in human colorectal liver metastases and two animal models. Masters thesis (M.Phil), UCL (University College London).

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Abstract

This thesis examines the perivascular innervation and ultrastructure of blood vessels in the normal human liver and colorectal liver metastases and compares them with two different animal models of liver metastases in order to examine their suitability for future pharmacological studies. Liver metastases and macroscopically normal liver from human resection specimens (n=13) and the two animal models (Hooded Lister rat with MC28 liver tumour, n=14 and nude rats with HT29 liver tumours, n=14) were studied immunohistochemically for the presence of various types of immunoreactive nerves. The ultrastructure and perivascular innervation of blood vessels supplying liver metastases were examined by transmission electron microscopy. In the normal human liver, perivascular immunoreactive (IR) nerve fibers containing PGP, NPY and TH were observed along the interlobular blood vessels, the sinusoids and the central vein of the hepatic lobule. The greatest density of immunoreactive nerve fibers was seen for PGP followed (in decreasing order) by NPY and TH. VIP, SP and CGRP immunoreactivity was observed only in nerve bundles associated with large interlobular vessels. SOM-IR, ANP-IR and AT II-IR nerves were absent. In contrast, no perivascular immunoreactive nerves were observed in colorectal liver metastases. Electron microscopy confirmed the absence of perivascular nerves in liver metastases. It also showed that the vessel walls were composed of a layer of endothelial cells surrounded by an incomplete, or very rarely in the periphery of the tumour a complete, layer of synthetic phenotype of smooth muscle-like cells. In the normal livers of nude and Hooded Lister rats perivascular immunoreactive nerve fibers containing PGP, NPY, TH, CGRP and SP (in dereasing densities) were observed around the interlobular blood vessels near the hilum and in the portal tracts. VIP immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In contrast, no perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves in both of these tumours. Smooth muscle cells were not observed in the vessel walls in these animal models. These results compared with those on human liver and colorectal liver metastases suggest that these two animal models may be suitable for pharmacological studies involving vascular manipulation for hepatic artery infusion chemotherapy.

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