Salviae miltiorrhizae ameliorates cirrhosis and portal hypertension by inhibiting nitric oxide in cirrhotic rats

OBJECTIVE: To determine the effect of Salviae miltiorrhizae on cirrhosis and portal hyperiension by inhibiting nitric oxide synthase type Ⅱ (NOSⅡ) in rats. METHODS: Real time RT-PCR was used to detect the expression of NOSII mRNA. The enzymatic activity of nitric oxide synthase and the circulating levels of nitric oxide (NO), systemic and portal hemodynamics, and quantification of cirrhosis were measured with highly sensitive methods. Traditional Chinese medicine was utilized to treat cirrhotic rats and the function of NO was evaluated. Double-blind method was applied in the experiment constantly. RESULTS: The concentration of NO increased markedly at all stages of cirrhosis, and so did the enzymatic activity of NOS, antl the iNOSmRNA expressed greatly. Meanwhile the portal-venous-pressure (PVP), portal-venous-now (PVF) increased significantly. NO, Nos and iNOSmHNA were positively correlated to the quanlity of hepatic fihrosis. Salviae Miltiorrhizae significantly inhibited NO production and inhibited the expression of iNOSmRNA. CONCLUSIONS: The increased hepatic expression of NoSIⅡ is one of the important factors causing cirrhosis and portal hypertension. Salviae Miltiorrhizae significantly ameliorates cirrhosis and portal hypertension.

Tetrandrine Ameliorates Cirrhosis and Portal Hypertension by Inhibiting Nitric Oxide in Cirrhotic Rats

To examine the role and effect of nitric oxide synthase type Ⅱ(NOSⅡ) in cirrhotic rats, expression of NOSⅡ mRNA was detected by real time RT-PCR. The enzymatic activity of nitric oxide synthase and the circulating levels of NO, systemic and portal hemodynamics and quantification of cirrhosis were measured. Chinese traditional medicine was used to treat cirrhotic rats and the effect of NO was evaluated. Double-blind method was used in experiment. Our results showed the concentration of NO and the enzymatic activity of NOS increased markedly at all stages of cirrhosis and iNOSmRNA was strongly expressed. Meanwhile, the portal-venous-pressure (PVP) and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the degree of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. Our results suggested that increased hepatic expression of NOSⅡ is one of the important factors causing cirrhosis and portal hypertension. Tetrandrine can significantly ameliorate cirrhosis and portal hypertension.

Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis

AIM： To investigate if sildenafil increases splanchnic blood flow and changes the hepatic venous pressure gradient （HVPG） in patients with cirrhosis. Phosphodiesterase type-5 inhibitors are valuable in the treatment of erectile dysfunction and pulmonary hypertension in patients with end-stage liver disease. However, the effect of phosphodiesterase type-5 inhibitors on splanchnic blood flow and portal hypertension remains essentially unknown. METHODS： Ten patients with biopsy proven cirrhosis （five females/five males, mean age 54：1：8 years） and an HVPG above 12 mmHg were studied after informed consent. Measurement of splanchnic blood flow and the HVPG during liver vein catheterization were done before and 80 min after oral administration of 50 mg sildenafil. Blood flow was estimated by use of indocyanine green clearance technique and Fick＇s principle, with correction for non-steady state. RESULTS： The plasma concentration of sildenafil was 222 ± 136 ng/mL 80 min after administration. Mean arterial blood pressure decreased from 77 ±7 mmHg to 66 ± 12 mmHg, P = 0.003, while the splanchnicblood flow and oxygen consumption remained unchanged at 1.14 ± 0.71 L/min and 2.3 ± 0.6 mmol/ min, respectively. Also the HVPG remained unchanged （18 ± 2 mmHg vs 16 ± 2 mmHg） with individual changes ranging from -8 mmHg to ±2 mmHg. In seven patients, HVPG decreased and in three it increased. CONCLUSION： In spite of arterial blood pressure decreases 80 min after administration of the phosphodiesterase type-5 inhibitor sildenafil, the present study could not demonstrate any clinical relevant influence on splanichnic blood flow, oxygen consumption or the HVPG.

Portal hemodynamics in cirrhotics with portal hypertension using color Doppler velocity profile

Objective To investigate portal hemodynamics and its correlation with e sophageal variceal bleeding (EVB) in cirrhotics with portal hypertension by usin g a newlydeveloped technique, color Doppler velocity profile (CDVP) Methods Hemodynamics of portal trunk (PT), right anterior branch (RAB) and splenic vein (SV) were evaluated in 48 cirrhotics with portal hypertension a nd 35 normal volunteers by CDVP The parameters included maximum crosssection a l velocity (CSVmax), flow volume, congestion index (CI), profile parameter N a nd pattern of flow curve Stepwise logistic regression model was employed to de termine EVBrelating factors in cirrhotics Results CSVmax in PT and RAB was significantly lower in cirrhotic gro up than that of normal group, being 1491308?cm/s, 944270?cm/s vs 3 052 675?cm/s, 1282269?cm/s, respectively ( P <001 for both) Fl ow volume of PT and SV was significantly higher in cirrhotic group compared with that of normal group, being 25161048?mlmin1kg1, 15 8 3918?mlmin1kg1 vs 2043557?mlmin1kg 1, 581 204?mlmin1kg1, respectively ( P <001 for bo th) C I of PT,RAB and SV was significantly higher in cirrhotic group than in normal gr oup, being 014200654, 010500496, 0088400431 vs 003260014 2, 0075 700342, 0048300230, respectively ( P <001 for all) In d ynami c variation of flow volume over time, RAB and SV in cirrhotic group increasingly presented flat pattern and periodically changed pattern, respectively ( P <001 for both) Between cirrhotic subgroups without and with EVB histor y, there were significant differences in flow volume, CI and N value of SV, splenic size, degree of esophageal varices (EV) and portal hypertensive gastropathy (PH G), and stepwise logistic regression revealed that N value of SV, splenic size, degree of EV and PHG were four independent factors in relation to EVB EVB sco r es calculated from the regression equation had a close correlation with EVB I n patients with EVB score>0, 889% of them had EVB, and in those with EVB<0, 76 9% of them had no history of EVB Conclusion In cirrhotics with portal hypertension, portal venous system has the features of elevated vascular resistance and hyperdynamics, and the lat ter mainly results from increased blood flow in SV EVB score may become a val uable parameter in predicting occurrence of EVB

Relationship between Abnormal Characteristics of Sublingual Collateral and Portal Vein Hemodynamic Changes in Patients with Primary Hepatic Carcinoma

Objective： To investigate the relationship between the abnormal characteristics of sublingual collateral （SC） and portal vein hemodynamic changes in patients with primary hepatic carcinoma （PHC）. Methods： A total of 123 patients of PHC with abnormal SC were enrolled. The SC characteristics were classified and evaluated. The principal components （PC） of SC extracted from them by principal component analysis and the relationship between PC and the dynamic changes of portal vein flow were analyzed by correlation analysis. Results： Three groups of PC were extracted, namely PC-1 （length, width, presentation type of visualization）, PC-2 （circuitous, vesicular change）, and PC-3 （color, collateral hemostasis, petechiae, ecchymosis）. Their total accumulative contribution degree reached 56.803%. Correlation analysis shows that PC-1 was significantly positively correlated with the hemodynamic parameters of the portal vein （P〈0.01）, while PC-2 and PC-3 were not （P〉0.05）. Conclusion： Length, width and presentation type of SC could be used for predicting the changes of portal venous pressure in PHC patients.

Effects of nitric oxide inhibitor on prostacyclin biosynthesis in portal hypertensive rats

Objective To evaluate the effects of nitric oxide inhibitor on prostacyclin (PGI 2) biosynthesis and the role of PGI 2 in hyperhemodynamics of portal hypertension. Methods Sprague Dawley rats were divided into four groups: intrahepatic portal hypertension (IHPH) by injection of CCl 4, prehepatic portal hypertension (PHPH) by stenosis of the portal vein, end to side portacaval shunt (PCS), and sham operated controls (SO). Animals of each group were subdivided into 2 groups: systemic administration of nitric oxide inhibitor L NMMA and vehicle. The radioactive microsphere method was used for hemodynamic study. The level of plasma PGI 2 (6 keto PGF 1α ) was measured by radioimmunoassay.Results The characteristics of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance, and splanchnic vascular resistance were observed in IHPH, PHPH and PCS rats. The magnitude of hyperhemodynamics was in the order of PCS>PHPH>IHPH rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L NMMA to the baseline values of hemodynamics in SO rats. The baseline concentrations of plasma 6 keto PGF 1α (ng/ml) in PHPH, IHPH, PCS, and SO rats were 6.93±2.43, 5.09±2.27, 2.36 ±1.01 and 1.56±0.61, respectively. The concentrations of plasma 6 Keto PGF 1α in PHPH,IHPH and PCS rats were significantly higher than those in SO rats. Moreover, the concentrations were significantly higher in PHPH and IHPH rats than in PCS rats (P<0.05). After administration of L NMMA, the concentrations of plasma 6 Keto PGF 1α (ng/ml) in PHPH, IHPH, PCS and SO rats were 7.69±2.98, 5.68 ±2.66, 5.50±0.79, 5.02±2.86, respectively. As compared to the baseline value, the concentrations of 6 keto PGF 1α rats were slightly increased in IHPH, PHPH rats (P>0.05), but significantly increased in PCS and SO rats (P<0.05).Conclusions In this study, the hyperdynamic circulatory state in portal hypertensive rats and portacaval shunt rats was completely reversed by L NNMA to normal, but the level of 6 keto PGF 1α was still elevated. The results indicate that PGI 2 is not involved in hyperhemodynamics of portal hypertension.