Portal hypertensive colopathy in patients with liver cirrhosis

AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis is indicated, especially those with worsening Child-Pugh class and/or decreasing platelet count, to prevent complications such as lower gastrointestinal bleeding.

Antioxidant role of heme oxygenase-1 in prehepatic portal hypertensive rats

AIM： To study the effect of bilirubin on the oxidative liver status and the activity and expression of heine oxygenase-1 （HO-1） in rat liver injury induced by prehepatic portal hypertension. METHODS： Wistar male rats, weighing 200-250 g, were divided at random into two groups： one group with prehepatic portal hypertension （PH） induced by regulated prehepatic portal vein ligation （PPVL） and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes, HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured. RESULTS： In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances （TBARS） content and a decrease in reduced glutathione （GSH） levels. The activities of liver antioxidant enzymes, superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GSH-Px） were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin （5μmol/kg body weight） 24 h before the end of the experiment entirely prevented all these effects. Pretreatment with Sn-protoporphyrin IX （Sn-PPIX） （100 μg/kg body weight, i.p.）, a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides, carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect CONCLUSION： These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.

Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats

AIM:To investigate any protective effect of early propranolol administration in the development of portal hypertensive gastropathy in cirrhotic rats. METHODS:For the development of liver cirrhosis and portal hypertensive gastropathy,60 rats underwent ligation of the left adrenal vein and complete devascularization of the left renal vein,followed by phenobarbital and carbon tetrachloride(CCl4) administration.After two weeks of CCl4 administration, the rats were randomly separated into two groups.In group A,propranolol was continuously administered intragastrically throughout the study,whereas in group B normal saline(placebo)was administered instead. Hemodynamic studies and vascular morphometric analysis of gastric sections were performed after complete induction of cirrhosis. RESULTS:Vascular morphometric studies showed higher numbers of vessels in all mucosal layers in the control group.Statistical analysis revealed a significantly higher total vascular surface in the control group compared to the propranolol group,but with no statistically significant difference between the mean vascular surfaces between the groups.Our study clearly shows that the increased mucosal blood flow is manifested by a marked increase of vessel count. CONCLUSION:Early propranolol's administration in portal hypertensive cirrhotic rats seems to prevent intense gastric vascular congestion that characterizes portal hypertensive gastropathy.

Helicobacter pylori and portal hypertensive gastropathy

To the Editor:H. pylori lives in the gastric epithelial cells, sometimes in gastric glands.Whetherornottheproliferationandbiologicalbehavior of H. pylori can be influenced by the status of the gastric mucosa is still unknown. Portal hypertensive gastropathy (PHG) is a blood drainage obstructive disease. In this pathologic environment, gastric mucosa may be further impaired when patients are infected with H. pylori. The role of H. pylori in the pathogenesis of PHG and

Experimental Study on the Correlation of Nitric Oxide with Portal Hypertensive Enteropathy

To explore the role of nitric oxide (NO) in the pathogenesis of portal hypertensive enteropathy (PHE), cirrhotic portal hypertension was induced in Wistar rats by subcutaneous administration of carbon tetrachloride. At the end of 12th week, NADPH-diaphorase staining was performed on ice frozen sections with the sample of fresh colonic tissues. NO synthase (NOS) activities and NOS mRNA expression of colonic tissues were investigated with chemoluminescence method and reverse transcription-polymerase chain reaction (RT-PCR), respectively. After NADPH-diaphorase histochemical staining, the computer image analysis and paired t test showed that NOS staining intensities of submucosal vascular endothelial cells and nerve fibers were all significantly higher in PHE group than those in normal group (P<0. 01 and P<0. 05, respectively), but the intensities of superficial epithelial cells were significantly lower than those of controls (P<0. 01). Chemoluminescence method demonstrated that general NOS activity of colonic mucosa was significantly higher in PHE group than that in control group (P<0. 01). Moreover, the degree of iNOS activity increase was greater than that of cNOS (104 % vs 35 %). RT-PCR revealed that NOS mRNA expressions were dramatically higher in PHE group than those in control group (P<0. 01). The results suggested that NO, with its property of vasodilatation, may be involved in the pathogenesis of vascular lesions of PHE in cirrhotic rats, and may also has something to do with mucosal lesions of colon in PHE.

Accuracy of virtual chromoendoscopy in differentiating gastric antral vascular ectasia from portal hypertensive gastropathy:A proof of concept study

BACKGROUND Accurate detection of gastric antral vascular ectasia(GAVE)is critical for proper management of cirrhosis-related gastrointestinal bleeding.However,endoscopic diagnosis of GAVE can be challenging when GAVE overlaps with severe portal hypertensive gastropathy(PHG).AIM To determine the added diagnostic value of virtual chromoendoscopy to high definition white light for real-time endoscopic diagnosis of GAVE and PHG.METHODS We developed an I-scan virtual chromoendoscopy criteria for diagnosis of GAVE and PHG.We tested our criteria in a cross-sectional cohort of cirrhotic adults with GAVE and PHG when high-definition white light endoscopy(HDWLE)diagnosis was in doubt.We then compared the accuracy of I-scan vs HDWLE alone to histology.RESULTS Twenty-three patients were included in this study(65.2%Caucasians and 60.9%males).Chronic hepatitis C was the predominant cause of cirrhosis(43.5%)and seven adults(30.4%)had confirmed GAVE on histology.I-scan had higher sensitivity(100%vs 85.7%)and specificity(75%vs 62.5%)in diagnosing GAVE compared to HDWLE.This translates into a higher,albeit not statistically significant,accuracy of I-scan in detecting GAVE compared to HDWLE alone(82%vs 70%).I-scan was less likely to lead to an accurate diagnosis of GAVE in patients on dialysis(P<0.05)and in patients with elevated creatinine(P<0.05).Iscan had similar accuracy to HDWLE in detecting PHG.CONCLUSION This pilot work supports that virtual chromoendoscopy may obviate the need for biopsies when the presence of GAVE is in doubt.Larger studies are needed to assess the impact of virtual chromoendoscopy on success of endoscopic therapy for GAVE.

Correlations of portal hypertensive gastropathy of hepatitis B cirrhosis with other factors

Objective: To study the clinical relations of portal hy- pertensive gastropathy (PHG) of hepatitis B cirrho- sis to other factors. Methods: Three groups of subjects were studied pro- spectively at our hospital from March 2000 to March 2001: 159 hepatitis B cirrhotic patients with portal hypertension, 114 hepatitis B cirrhotic patients with- out portal hypertension, and 97 control subjects. Free portal vein pressure (FPP) was measured dur- ing surgery. Liver function was assessed by Pugh's modification of Child's criteria. The area of liver collagen fibrin was studied using color image analysis system. Esophageal varices were identified by Dagra- di grading. Gastric varices were identified according to Northern Italian Endoscopic Council (NIEC) grading. Hypersplenism was assessed with the reduc- tion of WBC, HGB and PLT. Hepatitis B virus in the gastric mucosa was detected by immunizing histo- chemistry. Helicobacter pylori (H. pylori) organisms were identified by rapid urease testing and/or exami- nation of the stained biopsy specimens (haematoxylin and eosin). To analyze the correlation between these endoscopic signs at the gastric level and other fac- tors. Results: The differences of FPP among the three groups (patients with grade Ⅰ, Ⅱ, and Ⅲ gastropa- thy) were not significant. There was no correlation between Child-Pugh classification grading and the se- verity of gastropathy (P=0. 153). The differences of the area of liver collagen fibrin among the three grade gastropathy were not statistically significant (P =0. 801). There was a significant difference in the prevalence of severe PHG among grade Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ esophageal varices (P<0. 001). PHG was present in a similar percentage of patients with gas- tric varices compared with those without gastric vari- ces (P=0. 209). There was a significant difference in the severity between PHG and hypersplenism (P= 0. 003). Seven patients with PHG had no microscopic evidence of hepatitis B virus infection in the gastric wall. There was no correlation between Child-Pugh classification grading and infection of H. pylori (P= 0. 7491). Conclusions: The most important element causing PHG is the increased portal pressure as a prerequi- site. In addition, other factors may contribute to the development of PHG. PHG often occurs in patients with the presence of esophageal varices. There is a marked correlation between the severity of PHG and hypersplenism. Hepatitis B virus and H. pylori infec- tion are unlikely to be involved in the pathogenesis of PHG. The development of PHG is less influenced ei- ther by the severity of liver disease (Child-Pugh grade) and cirrhosis or by the presence or non pre- sence of gastric varices.

Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients

AIM： To assess the prevalence of portal hypertension （PH） related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH. METHODS： Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient （HVPG）. RESULTS： Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis wasalcoholism （45.5%）. Portal hypertensive colopathy （PHC） was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients （adenomatous type 65.2%）. One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices （GEV）, and 27.5% of patients with GEV presented with colopathy （P = 0.12）. A relationship between higher values of HVPG and presence of colopathy was observed （19.9：1：6.2 mmHg vs 16.8 ± 5.4 mmHg, P = 0.045）, but not with the grade of colopathy （P = 0.13）. Preneoplastic polyps and neoplasm （P = 0.02） and spontaneous bacterial peritonitis （P = 0.006） were more prevalent in patients with colopathy. We did not observe any association between previous β-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION： PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

Expression of TNF-α and VEGF in the esophagus of portal hypertensive rats

AIM: To investigate the expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) in the development of esophageal varices in portal hypertensive rats. METHODS: Thirty male Sprague-Dawley (SD) rats in the model group in which a two-stage ligation of portal vein plus ligation of the left adrenal vein was performed, were divided into three subgroups (M7, M14, and M21) in which the rats were kiued on the seventh day, the 14th d and the 21 d after the complete portal ligation. Thirty male SD rats, which underwent the sham operation in the control group, were also separated into three subgroups (C7, C14 and C21) corresponding to the models. The expression of TNF-α and VEGF in the esophagus of all the six subgroups of rats were measured with immunohistochemical SP technique. RESULTS: The portal pressure in the three model subgroups was significantly higher than that in the corresponding control subgroups (23.82±1.83 vs 11.61±0.86 cmH2O, 20.90±3.27 vs11.43±1.55 cmH2O and 20.68±2.27 vs 11.87±0.79 cmH2O respectively, vs P<0.01), as well as the number (9.3±1.6 vs 5.1?.8, 11.1±0.8 vs 5.4±1.3 and 11.7±1.5 vs 5.2?.1 respectively, P<0.01) and the total vascular area (78 972.6±3 527.8 vs 12 993.5±4 994.8 μm2, 107 207.5±4 6461.4 vs 11 862.6±5 423.2 μm2 and 110 241.4±49 262.2 vs 11 973.7±3 968.5 μm2 respectively, P<0.01) of submucosal veins in esophagus. Compared to the corresponding controls, the expression of TNP-α and VEGF in M21 was significantly higher (2.23±0.30 vs 1.13±0.28 and 1.65±0.38 vs 0.56±0.30 for TNF-α and VEGF respectively, P <0.01), whereas there was no difference in M7(1.14±0.38 vs 1.06±0.27 and 0.67±0.35 vs 0.50±0.24 for TNPa and VEGF respectively, P>0.05) and M14 (1.20±0.25 vs 1.04±0.26 and 0.65±0.18 vs 0.53±0.25 for TNF-α and VEGF respectively, P>0.05). And the expression of TNF-α and VEGF in M21 was significantly higher than that in M7 (2.23±0.30 vs1.14±0.38 and 1.65±0.38 vs 0.67±0.35 for TNF-α and VEGF respectively, P<0.01) and M14(2.23±0.30 vs 1.20±0.25 and 1.65±±0.38 vs 0.65±0.18 for TNF-a and VEGF respectively, P<0.01), but there was no difference between M7and M14(1.14±0.38 vs1.20±0.25 and 0.67±0.35 vs 0.65±0.18 for TNF-α and VEGF respectively, P>0.05). CONCLUSION: In the development of esophageal varices in portal hypertensive rats, increased TNF-α and VEGF may be not an early event, and probably play a role in weakening the esophageal wall and the rupture of esophageal varices.

Portal hypertensive duodenal polyp:A case report

Abnormalities of gastric mucosa in patients with portal hypertension are well documented. Manifestations of portal hypertension in small bowel and colon are less common. Colonic polypoid lesions microscopically consisting of a normal mucosa, with dilatation of submucosal vessels, have been described. We here report the first case of portal hypertensive duodenal polyp, responsible for gastro-intestinal bleeding. Endoscopic treatment turned out to be successful.

Expression of cyclooxygenase in hyperdynamic portal hypertensive rats

BACKGROUND: By detecting hemodynamic changes, concentration of plasm prostacyclin ( PGI2) and expression of cyclooxygenase( COX) in vasculature and splanchnic tissues, we evaluated the relative contributions of PGI2 and COX mRNA expression to the hyperdynamic circulatory state in chronic portal hypertensive rats. METHODS: Fifty male Sprague-Dawley rats were divided into 3 groups: intrahepatic portal hypertension (IHPH, n = 18) by injection of CCl4, prehepatic portal hypertension (PHPH, n = 18) by partial stenosis of the portal vein, and sham-operated controls (SO, n =14). Splanchnic hemodynamics was measured by radioactive microsphere techniques and the concentration of PGI2 was detected by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α. Semi-quantitive reverse transcriptase-polyme-rase chain reaction (RT-PCR) was performed to measure the levels of COX-1 mRNA and COX-2 mRNA in the thoracic aorta, superior mesenteric artery( SMA),and small intestine of IHPH, PHPH and SO rats, respectively. RESULTS: Hyperdynamic circulatory state was characterized by increased splanchnic blood flow and decreased splanchnic vascular resistance in IHPH and PHPH rats. The concentration of plasma 6-keto-PGF1α ( pg/ml) in IHPH (1093.75 ± 142.15) and PHPH (897. 42 ± 53. 29) rats was significantly higher than that in SO rats (730.13 ± 98. 67) (P <0.05). The expression of COX-1 mRNA in the thoracic aorta, SMA and small intestine was enhanced, whereas COX-2 mRNA expression was not detected in either of these vessels or the small intestine. The plasma 6-keto-PGF1α concentration and the expression of COX-1 mRNA in these vessels and the small intestine were closely correlated with such hemodynamic parameters as portal venous inflow (PVI), splanchnic vascular resistance (SVR) and free portal venous pressure (FPP) (P<0.05). CONCLUSION: The expression of COX-1 mRNA and the levels of PGI2 were closely related to the hyperdynamic circulatory state of portal hypertensive rats.

Hepatic lipid metabolism changes in short-and long-term prehepatic portal hypertensive rats

AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides,diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.

N-acetylcysteine modulates angiogenesis and vasodilation in stomach such as DNA damage in blood of portal hypertensive rats

AIM: To evaluate the antioxidant effect of N-acetylcysteine(NAC) on the stomach of rats with portal hypertension.METHODS: Twenty-four male Wistar rats weighing ± 250 g were divided into four experimental groups(n =6 each): Sham-operated(SO),SO + NAC,partial portal vein ligation(PPVL),and PPVL + NAC. Treatment with NAC in a dose of 10 mg/kg(i.p.) diluted in 0.6 m L of saline solution was administered daily for 7 d starting 8 d after the surgery. Animals from the PPVL and SO group received saline solution(0.6 m L) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15 th day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After,we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase(e NOS),vascular endothelial growth factor(VEGF),and nitrotirosine(NTT) proteins in stomach. We also evaluated e NOS and VEGF by Western blot analysis and assessed DNA damage in blood samples by the comet assay.RESULTS: The portal hypertension group exhibited increases in portal pressure when compared to SO group(29.8 ± 1.8 vs 12.0 ± 0.3 mm Hg)(P < 0.001). The same was observed when we compared the e NOS(56.8 ± 3.7 vs 13.46 ± 2.8 pixels)(P < 0.001),VEGF(34.9 ± 4.7 vs 17.46 ± 2.6 pixels)(P < 0.05),and NTT(39.01 ± 4.0 vs 12.77 ± 2.3 pixels)(P < 0.05) expression by immunohistochemistry of the PPVL animals with the SO group. The expression of e NOS(0.39 ± 0.03 vs 0.25 ± 0.03 a.μ)(P < 0.01) and VEGF(0.38 ± 0.04 vs 0.26 ± 0.04 a.μ)(P < 0.01) were also evaluated by Western blot analysis,and we observed an increase of both proteins on PPVL animals. We also evaluated the DNA damage by comet assay,and observed an increase on damage index and damage frequency on those animals. NAC decreased portal pressure values in PPVL + NAC animals(16.46 ± 2 vs 29.8 ± 1.8 mm Hg)(P < 0.001) when compared to PPVL. The expression of e NOS(14.60 ± 4.1 vs 56.8 ± 3.7 pixels)(P < 0.001),VEGF(19.53 ± 3.2 vs 34.9 ± 4.7 pixels)(P < 0.05) and NTT(21.84 ± 0.7 vs 39.01 ± 4.0 pixels)(P < 0.05) evaluated by immunohistochemistry were also reduced in PPVL + NAC animals. Also,when evaluated by Western blot e NOS expression(0.32 ± 0.03 vs 0.39 ± 0.03 a.μ)(P < 0.05) and VEGF expression(0.31 ± 0.09 vs 0.38 ± 0.04 a.μ)(P < 0.01). Furthermore,NAC modulated DNA damage in PPVL + NAC animals.CONCLUSION: In view of these results,we believe NAC is able to protect the stomach from the alterations induced by the PPVL procedure.

Role of PGI_2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.

Protective Effects of Hydrogen Sulfide on Portal Hypertensive Vasculopathy in Rabbits by Activating AKT-NF-κB Pathway

The role of hydrogen sulfide（H;S） in portal hypertension（PH）-induced esophagus-gastric junction vascular lesions in rabbits was observed. The rabbit PH models were established. The animals were randomly divided into the following groups: normal, PH, PH+sodium hydrosulfide（PH+S）, PH+propargylglycine（PH+PPG）. The plasma H;S levels, apoptosis of esophageal-gastric junction vascular smooth muscle cells, and the expression of nuclear transcription factor-κB（NF-κB）, p-AKT, IκBa and Bcl-2 were detected. The cystathionine γ lyase（cystathionine-gamma-splitting enzyme, CSE） in the junction vascular tissue was measured. The results showed that the plasma H;S levels and the CSE expression levels had statistically significant difference among different groups（P<0.05）. As compared with PH group, plasma H;S levels were declined obviously（11.9±4.2 vs. 20.6±4.5, P<0.05）, and CSE expression levels in the junction vascular tissue were notably reduced（1.7±0.6 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly decreased（0.10±0.15 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly decreased（2.31±0.33 vs. 3.04±0.38, P<0.05; 0.33±0.17 vs. 0.51±0.23, P<0.05）, however, IκBa and Bcl-2 expression increased obviously（5.57±0.17 vs. 3.67±0.13, P<0.05; 0.79±0.29 vs. 0.44±0.36, P<0.05） in PH+PPG group. As compared with PH group, H;S levels were notably increased（32.7±7.3 vs. 20.6±4.5, P<0.05）, the CSE levels in the junction vascular tissue were significantly increased（6.3±0.7 vs. 2.8±0.8, P<0.05）, apoptosis rate of vascular smooth muscle cells per unit area was significantly increased（0.35±0.14 vs. 0.24±0.07, P<0.05）, and the expression levels of p-AKT and NF-κB were significantly increased（4.29±0.49 vs. 3.04±0.38, P<0.05; 0.77±0.27 vs. 0.51±0.23, P<0.05）, yet IκBa and Bcl-2 expression decreased significantly（3.23±0.24 vs. 3.67±0.13, P<0.05; 0.31±0.23 vs. 0.48±0.34, P<0.05） in PH+S group. It is concluded that esophagus-gastric junction vascular lesions happen under PH, and apoptosis of smooth muscle cells is declined. H;S can activate NF-κB by the p-AKT pathway, leading to the down-regulation of Bcl-2, eventually stimulating apoptosis of vascular smooth muscle cells, easing PH. H;S/CSE system may play an important role in remission of PH via the AKT-NF-κB pathway.

Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.

Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, signif icantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modif ies the normal function in some brain regions.

Immunohistochemical Analysis of EGF-R in Gastric Mucosa in Portal Hypertensive with Cirrhosis

PAP Immunohistochemical technique was used to detect the expression and distribution of EGF-R in gastric mucosa in portal hypertensive pigs with cirrhosis. Our result showed that the EGF-R content in gastric mucosa of portal hypertensive pigs was significantly lower than that in control group. Microscopically, the portal hypertension (PHT) group imparted 'feeble positivity' or 'negative results' and the control group showed 'strong positivity '.It was suggested that the decrease of EGF-R content in gastric mucosa weakened defense mechanism of gastric mucosa and increase its vulnerability. It is believed that the decreased EGF-R in gastric mucosa is ascribed to the lesions of gastric mucosa during PHT with cirrhosis.

Portal Hypertensive Vascular Lesions

The aim of present study is to assess the pathological changes of gastric coronary vein in cirrhotic patients (n= 30) by immunohistochemical and morphological observation. The damage to endothelium, hypertrophy and hyperplasia of smooth muscle and increament of ECM were found in gastric coronary vein of cirrhotic patients. The vessel wall hardened and thickened with decrease of elasticity. The results showed that the portal hypertension could accompany with ' portal hypertensive vascular lesions'.