Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

In rats with portal hypertension induced by partial ligation of the portal vein, we have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. We evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 ± 0.89 vs. 4.18 ± 0.71 dyn.s.cm^-5 x 10⁴, mean ± SE, P<0.01), increased portal pressure (17.7 ± 0.9 vs. 9.5 ± 0.6 mmHg, P<0.001), and decreased portal venous inflow (3.93 ± 0.26 vs. 6.82 ± 0.49 ml.min^-1.100 g body wt^-1, P<0.001). In the following days rapid circulatory changes took place, and by the 8th day a new steady state was achieved characterized by the development of portal-systemic shunting (95.4 ± 3.3%), a decrease in portal resistance to control values, and an increase in portal venous inflow (8.10 ± 0.63 ml.min^-1.100 g body wt^-1, P<0.01) that contributes to the maintenance of an elevated portal pressure. These results demonstrate that, while the initial mechanism for portal hypertension in this model is due to a pure increase in resistance, subsequently portal venous inflow increases to play a more important role in the maintenance of portal hypertension.