Portacaval transposition and subsequent partial hepatectomy in the rat: A study of liver regeneration

Guest, Jonathan (1984) Portacaval transposition and subsequent partial hepatectomy in the rat: A study of liver regeneration. MD thesis, University of Glasgow.

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In the study presented in this thesis, portacaval transposition was carried out with in addition left adrenalectomy in the rat. Control operations included sham portacaval transposition with left adrenalectomy, left adrenalectomy alone and ether anaesthetic controls. Each animal was allowed to recover and was in good health 3 weeks later, by which time they had again reached a stable state. At that time a partial hepatectcmy was performed and liver regeneration monitored by measurement of liver weight and D.N.A. synthetic activity at multiple time points for the first 72 hours. Final liver weights were examined 3 weeks after partial hepatectomy and those values compared to a separate group of animals which were also a total of 6 weeks post-transposition or sham operation, and thus represented true controls for each procedure. We have shown from previous work (Ryan et al 1974) that the operation of portacaval transposition produces profound changes in the rat growth curve and also in relative liver weights. The work presented confirms the depressed growth rate after portacaval transposition compared to sham operated controls and this is even more marked after partial hepatectomy in the portacavally transposed rat. A reduction in relative liver weight is also confirmed. Hepatic tissue perfusion 3 weeks after portacaval transposition was shown to be not significantly different to controls. However, the 300% increase in liver blood flow seen after partial hepatectomy in the normal rat (Rice et al 1977) does not appear to occur after partial hepatectcmy in the portacavally transposed rat. The histology of the regenerating liver of the portacavally transposed rat revealed some differences from the control animals. Particularly, much more extensive fat infiltration of the liver which also persisted for a longer period. For all groups undergoing partial hepatectomy there was a peak of D.N.A. activity 21-24 hours after partial hepatectomy. During the first 36 hours after partial hepatectomy there was no significant difference either in magnitude or timing between rats previously subjected to portacaval transposition and those subjected to control procedures. This is the period which has been associated with hepatocyte replication in the rat (Bucher et al 1967). The alteration in relative liver weight after partial hepatectomy in the portacavally transposed animal was similar to controls during the first 48 hours, but was significantly lower at 72 hours. However, if the final relative liver weight at 3 weeks after partial hepatectomy in the portacavally transposed rat is compared with the expected relative liver weight 6 weeks after portacaval transposition, it does not differ significantly. Partial hepatectomy carried out 3 weeks after portacaval transposition plus left adrenalectomy in the rat results in a hyperplastic response of the hepatocyte which is similar in both timing and magnitude to controls. The relative liver weight 3 weeks after partial hepatectomy does not differ significantly from that expected. This response occurs despite the porta-prival state of the liver and without the dramatic rise in tissue perfusion seen in control animals. Any specific initiator of liver regeneration would, of course, reach the liver via the systemic circulation. If such a factor does exist, it is unaffected by passage through the general circulation. Specific portal hepatotrophic factors may exist and under normal circumstances may maintain the liver cell size and stability. Portal blood per se is not required to perfuse directly the hepatic portal bed for adequate regeneration on liver to occur.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine
Date of Award: 1984
Depositing User: Enlighten Team
Unique ID: glathesis:1984-76517
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 14:14
Last Modified: 19 Nov 2019 14:14
URI: https://theses.gla.ac.uk/id/eprint/76517

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