title: A pharmacodynamic model of portal hypertension in isolated perfused rat liver.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Xu
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Song
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Yin
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Peng-Tao
authors.initials: PT
authors.lastname: Li
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Cai
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D006505:Hepatitis / Q000150:complications / Q000503:physiopathology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008955:Models, Cardiovascular; D010656:Phenylephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D000109:Acetylcholine