A pharmacodynamic model of portal hypertension in isolated perfused rat liver

Figure 1 Group design of pharmacological model of portal hypertension. Oil indicated was administered subcutaneously with 3 mL/kg olive oil twice weekly for 84 d, as was CCl₄ + Oil 40% (v/v) CCl₄ in olive oil; IPPRL: Isolated portal perfused rat livers; EV₅₀: Median effective velocity; PE: Phenylephrine; Ach: Acetylcholine; CEC₅₀: Median effective concentration of PE constriction; REC₅₀: Median effective concentration of Ach relaxation; HE: Hematoxylin and eosin.

Figure 2 Collagen distributions in rat model livers (Masson × 40). Normal hepatic structure (d₀) was demonstrated in control rats administered 3 mL/kg olive oil subcutaneously twice weekly for 84 d. Hepatic degeneration (d₂₈), fibrosis (d₅₆) and cirrhosis (d₈₄) were seen in the chronic hepatitis model rats administered 3 mL/kg 40% (v/v) CCl₄ in olive oil subcutaneously twice weekly for 28 d, 56 d, and 84 d, respectively. There was less collagen mainly around the central veins (solid arrow) and the portal areas, with some staining noise signals in lobules (dashed arrow) in normal hepatic structure (d₀). The collagen fiber bundles (solid arrow) had partly spread into the lobules from the portal areas, the hepatic cells had obvious watery and fatty degeneration (dashed arrow) and had not been isolated by collagen during hepatic degeneration (d₂₈). The collagen fiber bundles (solid arrow) had completely separated some of the lobules to form many pseudo-lobules, several hepatic cells with obvious fatty degeneration (dashed arrow) had been completely isolated by collagen in hepatic fibrosis (d₅₆). The collagen fiber bundles (solid arrow) had limited smaller pseudo-lobules, some single hepatic cells (dashed arrow) were completely isolated by collagen in hepatic cirrhosis (d₈₄).

Figure 3 Phenylephrine elevates portal pressure (mean ± SE, n_i = 4). The dose-effect relationship between phenylephrine and portal vein constriction in isolated portal perfused rat livers without chronic hepatitis, where rats were administered 3 mL/kg olive oil subcutaneously twice per week for 84 d (control rats) (d₀). Rats with chronic hepatitis at three stages, hepatic degeneration (d₂₈), fibrosis (d₅₆) and cirrhosis (d₈₄), were administered 3 mL/kg 40% (v/v) CCl₄ in olive oil subcutaneously twice per week for 28 d, 56 d and 84 d, respectively. PE: Phenylephrine.

Figure 4 Acetylcholine reduces portal pressure (mean ± SE, n_i = 4). The dose-effect relationship between Acetylcholine and portal vein relaxation in isolated portal perfused rat livers without chronic hepatitis, where rats were administered 3 mL/kg olive oil subcutaneously twice per week for 84 d (control rats) (d₀). Rats with chronic hepatitis at three stages, hepatic degeneration (d₂₈), fibrosis (d₅₆) and cirrhosis (d₈₄), were administered 3 mL/kg 40% (v/v) CCl₄ in olive oil subcutaneously twice per week for 28 d, 56 d and 84 d, respectively. Ach: Acetylcholine.