Up-regulation of nNOS and associated increase in nitrergic vasodilation in superior mesenteric arteries in pre-hepatic portal hypertension

Portal hypertension in children is not uncommon and extra hepatic portal venous obstruction (EHPVO) constitute about 75% of portal hypertension. Several risk factors predispose to development of EHPVO such as neonatal sepsis, umbilical catheterization, severe dehydration, abdominal trauma or surgery etc. Common presentations are haematemesis and splenomegaly. Acute variceal bleeding is a medical emergency. Liver function is normal in extrahepatic portal hypertension unless there is portal bilopathy. High index of suspicion is the key of early diagnosis. Esophagogastrodudenoscopy is diagnostic for portal hypertension and doppler ultrasonography of portal vein confirm extra hepatic portal venous obstruction (EHPVO) in presence of thrombus and/or cavernoma. Adequate management including endotherapy, pharmacotherapy and/or surgery is an important key for better outcome. Mediscope Vol. 6, No. 2: Jul 2019, Page 79-85

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Tu1010 Noninvasive Methods in Predicting Large Esophageal Varices in Pediatric Patients With Intra-Hepatic Portal Hypertension, According to Child-Pugh Classification

Gastroenterology ◽

10.1016/s0016-5085(13)63833-0 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-1031 ◽

Cited By ~ 1

Author(s):

Marina R. Adami ◽

Cristina Targa Ferreira ◽

Vania Hirakata ◽

Sandra Maria G. Vieira ◽

Carlos O. Kieling

Keyword(s):

Portal Hypertension ◽

Esophageal Varices ◽

Pediatric Patients ◽

Noninvasive Methods ◽

Hepatic Portal

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Hepatic venoconstriction is involved in anaphylactic hypotension in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00368.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1436-H1441 ◽

Cited By ~ 39

Author(s):

Toshishige Shibamoto ◽

Sen Cui ◽

Zonghai Ruan ◽

Wei Liu ◽

Hiromichi Takano ◽

...

Keyword(s):

Portal Hypertension ◽

Venous Pressure ◽

Liver Weight ◽

Systemic Arterial Pressure ◽

Mesenteric Arteries ◽

Isolated Perfused Rat Liver ◽

Circulating Blood Volume ◽

Anesthetized Rats ◽

Occlusion Technique ◽

Vascular Beds

We determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats and the effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused rat livers. In anesthetized rats sensitized with ovalbumin (1 mg), an intravenous injection of 0.6 mg ovalbumin caused not only a decrease in systemic arterial pressure from 120 ± 9 to 43 ± 10 mmHg but also an increase in portal venous pressure that persisted for 20 min after the antigen injection (the portal hypertension phase). The elimination of the splanchnic vascular beds, by the occlusions of the celiac and mesenteric arteries, combined with total hepatectomy attenuated anaphylactic hypotension during the portal hypertension phase. For the isolated perfused rat liver experiment, the livers derived from sensitized rats were hemoperfused via the portal vein at a constant flow. Using the double-occlusion technique to estimate the hepatic sinusoidal pressure, presinusoidal ( Rpre) and postsinusoidal ( Rpost) resistances were calculated. An injection of antigen (0.015 mg) caused venoconstriction characterized by an almost selective increase in Rpre rather than Rpost and liver weight loss. Taken together, these results suggest that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably because of anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension.

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Ergotamine abuse and extra-hepatic portal hypertension.

Postgraduate Medical Journal ◽

10.1136/pgmj.61.715.461 ◽

1985 ◽

Vol 61 (715) ◽

pp. 461-463 ◽

Cited By ~ 7

Author(s):

P. E. Fisher ◽

D. B. Silk ◽

N. Menzies-Gow ◽

M. Dingle

Keyword(s):

Portal Hypertension ◽

Hepatic Portal

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Portal hypertension increases vasoconstrictor responsiveness of rat aorta

Clinical Science ◽

10.1042/cs0960041 ◽

1999 ◽

Vol 96 (1) ◽

pp. 41-47 ◽

Cited By ~ 6

Author(s):

Claire CONNOLLY ◽

Teresa CAWLEY ◽

P. Aiden MCCORMICK ◽

James R. DOCHERTY

Keyword(s):

Portal Hypertension ◽

Wistar Rats ◽

Rat Aorta ◽

Maximum Response ◽

Sprague Dawley ◽

Portal Vein Stenosis ◽

Sprague Dawley Rats ◽

Significant Difference ◽

Hepatic Portal

We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine (0.86±0.10 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45±0.04 ;g, 0.57±0.07 ;g, 0.71±0.05 ;g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21±0.21 ;g) and phenylephrine (1.54±0.30 ;g) but not noradrenaline (0.93±0.09 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59±0.09 ;g, 0.76±0.11 ;g, 1.04±0.10 ;g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to α1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.

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COX-2/sEH Dual Inhibitor PTUPB Alleviates CCl4-Induced Liver Fibrosis and Portal Hypertension

Frontiers in Medicine ◽

10.3389/fmed.2021.761517 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhifeng Zhao ◽

Chihao Zhang ◽

Jiayun Lin ◽

Lei Zheng ◽

Hongjie Li ◽

...

Keyword(s):

Liver Cirrhosis ◽

Portal Hypertension ◽

Growth Factor ◽

Liver Fibrosis ◽

Vascular Remodeling ◽

Mesenteric Arteries ◽

Cytokeratin 19 ◽

Dual Inhibitor ◽

Bile Duct Proliferation ◽

Cox 2

Background: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl) -benzenesulfonamide (PTUPB), a dual cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) inhibitor, was found to alleviate renal, pulmonary fibrosis and liver injury. However, few is known about the effect of PTUPB on liver cirrhosis. In this study, we aimed to explore the role of PTUPB in liver cirrhosis and portal hypertension (PHT).Method: Rat liver cirrhosis model was established via subcutaneous injection of carbon tetrachloride (CCl4) for 16 weeks. The experimental group received oral administration of PTUPB (10 mg/kg) for 4 weeks. We subsequently analyzed portal pressure (PP), liver fibrosis, inflammation, angiogenesis, and intra- or extrahepatic vascular remodeling. Additionally, network pharmacology was used to investigate the possible mechanisms of PTUPB in live fibrosis.Results: CCl4 exposure induced liver fibrosis, inflammation, angiogenesis, vascular remodeling and PHT, and PTUPB alleviated these changes. PTUPB decreased PP from 17.50 ± 4.65 to 6.37 ± 1.40 mmHg, reduced collagen deposition and profibrotic factor. PTUPB alleviated the inflammation and bile duct proliferation, as indicated by decrease in serum interleukin-6 (IL-6), liver cytokeratin 19 (CK-19), transaminase, and macrophage infiltration. PTUPB also restored vessel wall thickness of superior mesenteric arteries (SMA) and inhibited intra- or extrahepatic angiogenesis and vascular remodeling via vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), etc. Moreover, PTUPB induced sinusoidal vasodilation by upregulating endothelial nitric oxide synthase (eNOS) and GTP-cyclohydrolase 1 (GCH1). In enrichment analysis, PTUPB engaged in multiple biological functions related to cirrhosis, including blood pressure, tissue remodeling, immunological inflammation, macrophage activation, and fibroblast proliferation. Additionally, PTUPB suppressed hepatic expression of sEH, COX-2, and transforming growth factor-β (TGF-β).Conclusion: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)- benzenesulfonamide ameliorated liver fibrosis and PHT by inhibiting fibrotic deposition, inflammation, angiogenesis, sinusoidal, and SMA remodeling. The molecular mechanism may be mediated via the downregulation of the sEH/COX-2/TGF-β.

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Warren shunt combined with partial splenectomy in children with extra-hepatic portal hypertension, massive splenomegaly and severe hypersplenism

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1408419s ◽

2014 ◽

Vol 142 (7-8) ◽

pp. 419-423 ◽

Cited By ~ 2

Author(s):

Aleksandar Sretenovic ◽

Vojislav Perisic ◽

Dragana Vujovic ◽

Dragan Opacic ◽

Vojkan Vukadinovic ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Function Tests ◽

Safe Procedure ◽

Shunt Surgery ◽

Warren Shunt ◽

Portal Vein Obstruction ◽

Z Scores ◽

Hepatic Portal Vein ◽

One Year ◽

Hepatic Portal

Introduction. Extra-hepatic portal vein obstruction (EHPVO) is one of the most often causes of portal hypertension in children. Objective. Establishing the importance of shunt surgery in combination with partial spleen resection in selected pediatric patients with EHPVO, enormous splenomegaly and severe hypersplenism. Methods. Distal splenorenal shunt (DSRS) with partial spleen resection was performed in 22 children age from 2 to 17 years with EHPVO. Indications for surgery were pain and abdominal discomfort caused by spleen enlargement, as well as symptomatic hypersplenism with leucopenia, thrombocytopenia and anemia. The partial spleen resection was performed by ligation of blood vessels to caudal two thirds of the spleen. After ischemic parenchymal demarcation transection with electrocautery LigaSure was performed with preservation of 20-30% of spleen tissue, and then Warren DSRS was created. Platelet and leucocytes counts and liver function tests were obtained before, one month and one year after surgery. Growth was assessed with SD scores (Z scores) for height, weight and body mass index at the time of surgery and one year later. Results. In all patients postoperative period was without significant complications. Platelets and leucocytes counts were normalized. Patency rate of shunts was 100%. Two significant shunts stenosis were observed and successfully treated with percutaneous angioplasty. During the follow-up period (1 to 9 years) all patients were asymptomatic, with improved quality of life and growth. Conclusion. Results of our study indicate that shunt surgery with a partial spleen resection is an effective and safe procedure for patients with enormous splenomegaly and severe hypersplenism caused by EHPVO.

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