A pharmacodynamic model of portal hypertension in isolated perfused rat liver

AIM: To develop a pharmacodynamic model of portal hypertension from chronic hepatitis.METHODS: Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl₄-induced chronic hepatitis. At d₀, d₂₈, d₅₆ and d₈₄ of the process, the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump. The pressure (mmHg) was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.RESULTS: At d₀, d₂₈, d₅₆ and d₈₄, the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y = 0.1732 + 0.3970/1 + 10^{(-4.3061-0.4407 X)}], Y = -0.004934 + 0.12113/1 + 10^{(-3.1247-0.3262 X)}], Y = 0.0104 + 0.2643/1 + 10^{(-8.8462-0.9579 X)}], and Y = 0.01603 + 0.12107/1 + 10^{(-5.1134-0.563 X)}]; the median effective concentrations were 1.69 × 10^-10 mol/L, 2.64 × 10^-10 mol/L, 5.82 × 10^-10 mol/L, and 8.24 × 10^-10 mol/L, respectively. The equations from the concentrations of acetylcholine used to relax the portal vein were Y = -0.4548 + 0.3274/1 + 10^{(6.1538 + 0.5554 X)}], Y = -0.05391 + 0.06424/1 + 10^{(3.8541 + 0.3469 X)}], Y = -0.2733 + 0.22978/1 + 10^{(3.0472 + 0.3008 X)}], and Y = -0.0559 + 0.053178/1 + 10^{(5.6336 + 0.5883 X)}]; the median effective concentrations were 8.40 × 10^-10 mol/L, 7.73 × 10^-12 mol/L, 5.98 × 10^-11 mol/L, and 2.66 × 10^-10 mol/L, respectively.CONCLUSION: A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.