A pharmacodynamic model of portal hypertension in isolated perfused rat liver

Table 1 Hepatic pathological changes in model rats (mean ± SE, n_i = 8)

Advanced	Lobule ratio	Collagen ratio
d0	0.38 ± 0.05	0.0000700 ± 0.0001180
d28	0.33 ± 0.04b	0.0019658 ± 0.0024864b
d56	0.11 ± 0.04b,d	0.0043315 ± 0.0048768b,d
d84	0.06 ± 0.01b,d,f	0.0143996 ± 0.0143860b,d,f

Lobule ratio is the average percentage obtained from ten random fields using Image-Pro Plus v 5.1 software, and each field had a ratio of lobule area per total analyzed field area in hematoxylin-eosin stained sections under a Digital Pathology System at × 20 magnification from isolated portal perfused rat livers. Collagen ratio is the average percentage obtained from ten random fields using Image-Pro Plus v 5.1 software, and each field had a ratio of collagen area per total analyzed field area in Masson-stained sections under a Digital Pathology System at × 40 magnification from isolated portal perfused rat livers. a and b denote significant (^bP ＜ 0.01) differences between those at d₀ and at d₂₈, d₅₆, or d₈₄. c and d denote significant (^cP ＜ 0.05 and ^dP ＜ 0.01) differences at d₂₈ and at d₅₆, or d₈₄. e and f denote significant (^eP ＜ 0.05 and ^fP ＜ 0.01) differences at d₅₆ and at d₈₄.

Table 2 Phenylephrine elevates portal pressure (mean ± SE, n_i = 4)

Log[PE (mol/L)]	d0	d2	d56	d84
-12	0.210 ± 0.19	0.013 ± 0.02	0.013 ± 0.02	0.019 ± 0.03
-11	0.260 ± 0.16	0.025 ± 0.03	0.017 ± 0.02	0.024 ± 0.04
-10	0.360 ± 0.18	0.044 ± 0.06	0.046 ± 0.06	0.047 ± 0.07
-9	0.420 ± 0.24	0.072 ± 0.09	0.182 ± 0.25	0.076 ± 0.09
-8	0.550 ± 0.37	0.090 ± 0.12	0.247 ± 0.27	0.119 ± 0.10
-7	0.520 ± 0.37	0.093 ± 0.12	0.269 ± 0.27	0.123 ± 0.11
-6	0.570 ± 0.24	0.113 ± 0.13	0.286 ± 0.28	0.138 ± 0.12

Primary data were used to calculate the dose-effect relationship between phenylephrine and portal vein constriction in the 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.

Table 3 Acetylcholine reduces portal pressure (mean ± SE, n_i = 4)

Log[Ach (mol/L)]	d0	d28	d56	d84
-13	-0.16 ± 0.12	-0.002 ± 0.01	-0.076 ± 0.08	-0.001 ± 0.01
-12	-0.19 ± 0.10	-0.009 ± 0.01	-0.091 ± 0.10	-0.006 ± 0.01
-11	-0.31 ± 0.07	-0.025 ± 0.01	-0.125 ± 0.15	-0.012 ± 0.01
-10	-0.39 ± 0.08	-0.035 ± 0.18	-0.176 ± 0.23	-0.019 ± 0.01
-9	-0.42 ± 0.08	-0.043 ± 0.04	-0.203 ± 0.26	-0.041 ± 0.02
-8	-0.44 ± 0.12	-0.049 ± 0.05	-0.225 ± 0.26	-0.050 ± 0.03
-7	-0.47 ± 0.14	-0.052 ± 0.07	-0.256 ± 0.28	-0.054 ± 0.03

Primary data were used to calculate the dose-effect relationship between acetylcholine and portal vein relaxation in the 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.