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.