scholarly journals Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats

2021 ◽  
Author(s):  
Hui-Chun Huang ◽  
Ming-Hung Tsai ◽  
Ching-Chih Chang ◽  
Chon Kit Pun ◽  
Yi-Hsiang Huang ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Liver Injury ◽  
Portal Pressure ◽  
Vascular Density ◽  
Variceal Hemorrhage ◽  
Distribution Method ◽  
Portosystemic Shunts ◽  
Duct Ligation ◽  
Portosystemic Collaterals

Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P = .010, .044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated eNOS was downregulated. Portosystemic shunts determined by splenorenal shunt flow decreased in both transplantation groups (P = .037, .032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared to sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

scholarly journals The beneficial effects of curcumin in cirrhotic rats with portal hypertension

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Shao-Jung Hsu ◽  
Jing-Yi Lee ◽  
Te-Yueh Lin ◽  
Yu-Hsin Hsieh ◽  
Hui-Chun Huang ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Vascular Resistance ◽  
Portal Pressure ◽  
Acute Administration ◽  
Vegf Receptor ◽  
Variceal Hemorrhage ◽  
Common Bile Duct Ligation ◽  
Duct Ligation ◽  
Portosystemic Collaterals

In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague–Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral in situ perfusion was performed to evaluate vascular activity. Chronic curcumin treatment decreased portal pressure (PP), cardiac index (CI) and increased systemic vascular resistance (SVR) in cirrhotic rats. In splanchnic system, curcumin decreased superior mesenteric artery (SMA) flow and increased SMA resistance. Mesenteric angiogenesis was attenuated by curcumin. Acute administration of curcumin significantly induced splanchnic vasoconstriction. The mesenteric protein expressions of p-endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX) 2 (COX2), vascular endothelial growth factor (VEGF), p-VEGF receptor 2 (VEGFR2), and p-Erk were down-regulated. In collateral system, curcumin decreased portosystemic shunting and induced vasoconstriction. In conclusion, chronic curcumin administration in cirrhotic rats ameliorated portal hypertension related hemodynamic derangements and portosystemic collaterals. Curcumin also attenuated splanchnic hyperdynamic circulation by inducing vasoconstriction through inhibition of eNOS activation and by decreasing mesenteric angiogenesis via VEGF pathway blockade.

scholarly journals Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats

2019 ◽  
Vol 20 (17) ◽  
pp. 4161
Author(s):  
Ting Chang ◽  
Hsin-Ling Ho ◽  
Shao-Jung Hsu ◽  
Ching-Chih Chang ◽  
Ming-Hung Tsai ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Bile Duct ◽  
Portal Pressure ◽  
Sham Operation ◽  
Duct Ligation ◽  
Phosphorylated Akt ◽  
Protein Expressions ◽  
Portosystemic Shunting ◽  
Portosystemic Collaterals

Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3′-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.

Insulin reverses major portal hypertension-related derangements in rats with liver cirrhosis and diabetes

2018 ◽  
Vol 132 (22) ◽  
pp. 2391-2405
Author(s):  
I-Fang Hsin ◽  
Hui-Chun Huang ◽  
Ching-Chih Chang ◽  
Shao-Jung Hsu ◽  
Fa-Yauh Lee ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Perfusion ◽  
Diabetic Rats ◽  
Vascular Density ◽  
Diabetic Patients ◽  
Common Bile Duct Ligation ◽  
Portal Hemodynamics ◽  
Duct Ligation ◽  
Protein Expressions ◽  
Portosystemic Collaterals

Liver cirrhosis is accompanied by increased intrahepatic resistance and angiogenesis-related portosystemic collaterals formation. Diabetic patients suffer from abnormal vasoresponsiveness and angiogenesis that can be ameliorated by glucose control. However, the relevant presentation is not clear in those with cirrhosis and diabetes, in whom insulin is the treatment of choice. Liver cirrhosis was induced in Sprague–Dawley rats with common bile duct ligation (BDL) and sham rats were used as controls. Streptozotocin 60 mg/kg (STZ, i.p., to induce diabetes) or vehicle was injected. The rats received BDL and STZ injections were injected with insulin or vehicle. On the 29th day after the procedure, the groups were surveyed for (1) systemic and portal hemodynamics; (2) mesenteric vascular density; (3) severity of portosystemic collaterals; (4) hepatic resistance using in situ liver perfusion; (5) histology survey of mesentery and liver; and (6) mesentery angiogenesis- and liver fibrogenesis-related protein expressions. Compared with the cirrhotic rats, the cirrhotic diabetic rats had lower body weight, cardiac output, superior mesenteric arterial (SMA) resistance and portal venous (PV) resistance, and higher SMA and PV flow, which were mostly reversed by insulin. The cirrhotic diabetic rats also had increased mesenteric vascular density, and enhanced pERK, pAkt, VEGF, VEGFR2 protein expressions that were reversed by insulin. Insulin decreased the degree of shunting in the diabetic cirrhotic rats. Hepatic perfusion pressure and severity of liver fibrosis were not significantly influenced by diabetes and insulin treatment in the cirrhotic rats. In conclusion, diabetes aggravated hemodynamic derangements, mesenteric angiogenesis and collaterals in the cirrhotic rats, which were mostly ameliorated by insulin. Further clinical investigations are warranted.

scholarly journals Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats

2021 ◽  
Vol 22 (14) ◽  
pp. 7662
Author(s):  
Chon Kit Pun ◽  
Hui-Chun Huang ◽  
Ching-Chih Chang ◽  
Chiao-Lin Chuang ◽  
Chun-Hsien Yen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Statistical Significance ◽  
Portal Pressure ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Duct Ligation ◽  
The Impact

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation

2021 ◽  
pp. 096452842110392
Author(s):  
Yu-Sheng Chen ◽  
Chorng-Kai Wen ◽  
Geng-Hao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Portal Hypertension ◽  
Growth Factor ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Portal Pressure ◽  
Contractile Responses ◽  
Hyperdynamic Circulation ◽  
Duct Ligation ◽  
Tnf Α ◽  
Cox 1

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

The Effect of Artificial Portocaval Anastomosis or Splenectomy on Hepatic and Portal Haemodynamics in Cirrhotics

1969 ◽  
Vol 08 (03) ◽  
pp. 232-241
Author(s):  
J. Vosmík ◽  
V. Bláha
Keyword(s):  
Blood Flow ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Liver Blood Flow ◽  
Severe Liver ◽  
Portocaval Anastomosis ◽  
Average Decrease ◽  
Modified Method ◽  
Portosystemic Shunts ◽  
Before And After

SummaryUsing their own modified method the authors simultaneously examined the blood clearances of 198Au colloid and 131I-Rose Bengal and determined the ratio1. in a group of 11 patients with severe liver cirrhosis, portal hypertension and portosystemic shunts, both before and after artificial portocaval anastomosis, and2. in two patients with thrombosis v. lienalis, excessive splenomegaly and extensive portosystemic shunts before and after splenectomy. Ad 1. In 6 patients 55%) a reduction of the effective liver blood flow occured due to the artificial portosystemic anastomosis; the average decrease was ~ 20%. In 7 patients a significant enlargement of the total splenosystemic flow was observed as a result of the artificial communication.Ad 2. In both patients an increase of the effective liver blood flow occured after splenectomy. The minimal preoperative splenosystemic flow was ~ 0.152 and ~ 0.089 of the circulating blood per minute (expressed by means of kAu).The authors discuss the significance of the kAu and kBR values as well as that of the ratio for the estimation of changes in hepatic and portal haemodynamics.

scholarly journals Spontaneous portosystemic shunts in liver cirrhosis: new approaches to an old problem

2020 ◽  
Vol 13 ◽  
pp. 175628482096128 ◽  
Author(s):  
Judit Vidal-González ◽  
Sergi Quiroga ◽  
Macarena Simón-Talero ◽  
Joan Genescà
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Encephalopathy ◽  
Portosystemic Shunt ◽  
Venous System ◽  
Variceal Hemorrhage ◽  
Portal Venous System ◽  
Portal Flow ◽  
Portosystemic Shunts ◽  
Intrahepatic Portosystemic Shunt

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive.

Combined endoscopic intervention (ligation+sclerotherapy) compared with TIPS for prevention of bleeding from gastro-esophageal varices in patients with liver cirrhosis

2016 ◽  
Vol 5 (1) ◽  
pp. 124
Author(s):  
Utkirbek Matkuliev
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Varicose Veins ◽  
Portal System ◽  
Endoscopic Intervention ◽  
Portosystemic Shunts ◽  
System Pressure ◽  
Intrahepatic Portosystemic Shunt ◽  
History Of ◽  
The Mean

Background: Liver cirrhosis (LC) and portal hypertension (PH) is one of the most serious problems of modern surgical hepatology. The most common complication of liver cirrhosis is bleeding from varicose veins of esophagus and stomach. Today experts have several ways to prevent rebleeding from varices: pharmacotherapy, endoscopic intervention, transjugular intrahepatic portosystemic shunt (TIPS), a surgical portocaval bypass. Purpose of this study was to compare effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) and combined endoscopic therapy the management of bleeding in cirrhotic patients.Methods: We observed 96 consecutive patients with portal hypertension who were treated in 2nd clinic of Tashkent Medical Academy (2014-2015). Bleeding was in history of 17 (17.7%) patients. The duration of the bleeding averaged 9.7±4.3 hours. Ascites was observed in 54.5 % of patients. Patients were divided two major groups. First group included 72 patients who was performed endoscopic intervention. Second group consisted of 24 patients who underwent TIPS in emergency cases.Results: Seventy-two patients were assigned to variceal ligation and Sclerotherapy, other 24 patients to TIPS. In the ligation combined Sclerotherapy group, a second treatment was performed 8–10 days after the initial endoscopy. Deterioration of portal gastropathy was observed in 9 (9.4%) cases after EL and 24 (25.0%) after ES (p <0.05). The mean portal system pressure prior to TIPS placement was 53.67±4.21 mm Hg, which decreased to 25.10±4.06 mmHg after the first shunt tract was established (P <0.001). The mean portal system pressure prior to the second TIPS was 43.68±3.98 mm Hg and decreased to 25.14±4.67 mm Hg after the procedures (P <0.001).Conclusions: TIPS can become dysfunctional if stenosis develops in the shunt or the hepatic vein above the shunt. Screening allows detection of stenosis before portal hypertensive–related complications recur. Revision of stenotic shunts can be easily accomplished in most cases. Techniques for screening and revision will be discussed. This is one of the most effective methods to control patients with liver cirrhosis.

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