Induced Liver Hyperplasia

The liver strictly regulates its own volume relative to body mass. We aim to investigate and manipulate the mechanisms underlying this phenomenon. Based on increasing evidence that regeneration after partial hepatectomy (PHx) is triggered immediately by changes in hemodynamics, we have designed and tested through a series of trials, a surgical experimental model of partial portal vein arterialisation (PPVA) in the pig. The controlled shunting of arterial blood from the aorta to the portal vein branch su pplying liver segments II, II and IV creates a hyperdynamic flow and increased sinusoidal shear stress, hypothetically inducing selective hyperplasia in the arterially perfused area resulting in a supranormal liver weight/body mass ratio surpassing the na tural confinements of liver growth. The hypothesis that increased sinusoidal shear stress results in induced liver hyperplasia, possibly by the same molecular mechanisms seen after PHx, will be examined in a chronic series where the animals undergo a PPV A, which they bear for 21 days after which liver weight and volume changes and BrDu incorporation are measured. To better understand the mechanisms surrounding liver regeneration and hyperplasia, and how these may be manipulated, the molecular-genetic, metabolic, hemodynamic, ultrastructural, biochemical and extracellular matrix component changes occurring during PPVA will be examined in detail in an acute series. Should the metabolic profiles attained from segments II, III and IV by microdialysis reve al the expression of specific growth factors and cytokines, then further experiments will be planned aimed at inducing liver growth by utilizing these substances.