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Sample records for portal hypertensive rats

  1. Portal Hypertension

    MedlinePlus

    ... Chronic Hepatitis C Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD NOTE: This is ... Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  2. Adrenal dysfunction in portal hypertensive rats with acute hemorrhage.

    PubMed

    Lee, Fa-Yauh; Wang, Sun-Sang; Tsai, Ming-Hung; Huang, Hui-Chun; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the 'hepatoadrenal syndrome', but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  3. Adrenal Dysfunction in Portal Hypertensive Rats with Acute Hemorrhage

    PubMed Central

    Lee, Fa-Yauh; Wang, Sun-Sang; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the ‘hepatoadrenal syndrome’, but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  4. Restriction of drinking water abrogates splanchnic vasodilation and portal hypertension in portal vein-ligated rats.

    PubMed

    Heinemann, Akos; Schuligoi, Rufina; Lippe, Irmgard T; Stauber, Rudolf E

    2009-01-01

    Portal hypertension is associated with splanchnic vasodilation which is claimed responsible for the maintenance of chronically elevated portal pressure. Vasopressin analogues are used in the treatment of acute variceal bleeding, since they effectively reduce splanchnic blood flow and portal pressure. Dehydration stimulates the release of endogenous vasopressin release. Here we compared the effects of deprivation of drinking water for 18 h with those of vasopressin infusion on mesenteric hemodynamics in portal vein-ligated (PVL) and sham-operated (SHAM) rats. Blood flow in the superior mesenteric artery was measured with the ultrasonic transit time shift technique. Deprivation of drinking water had no hemodynamic effects in SHAM rats, but completely reversed the mesenteric hyperemia and portal hypertension in PVL rats to figures measured in SHAM rats, without altering blood pressure. Similarly, intravenous infusion of low doses of arginine vasopressin (1-10 pmol/min) selectively reduced mesenteric blood flow in PVL rats but had little effect in SHAM rats. These data suggest that control of water balance or aquaretic drugs might have beneficial effects on splanchnic hemodynamics and portal pressure in advanced liver disease, possibly by stimulating endogenous vasopressin release. PMID:18987488

  5. Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta.

    PubMed Central

    Cawley, T; Geraghty, J; Osborne, H; Docherty, J R

    1995-01-01

    1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. 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. PMID:7773539

  6. Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

    SciTech Connect

    Sikuler, E.; Kravetz, D.; Groszmann, R.J.

    1985-06-01

    In rats with portal hypertension induced by partial ligation of the portal vein, the authors have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. The authors evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 +/- 0.89 vs. 4.18 +/- 0.71 dyn X s X cm-5 X 10(4), mean +/- SE, P less than 0.01), increased portal pressure (17.7 +/- 0.9 vs. 9.5 +/- 0.6 mmHg, P less than 0.001), and decreased portal venous inflow (3.93 +/- 0.26 vs. 6.82 +/- 0.49 ml X min-1 X 100 g body wt-1, P less than 0.001).

  7. Effects of propranolol and sucralfate on ethanol-induced gastric mucosal damage in chronic portal hypertensive rats.

    PubMed

    Geoffroy, P; Duchateau, A; Thiéfin, G; Zeitoun, P

    1987-10-01

    In a rat model of chronic portal hypertension we studied ethanol-induced gastric mucosal damage and the effects of pretreatment by propranolol and sucralfate. Susceptibility to ethanol was increased in chronic portal hypertensive rats compared with sham-operated rats (55 +/- 8% vs. 25 +/- 4%). Both acute pretreatment (10 min) and chronic pretreatment (3 weeks) with propranolol reduced gastric mucosal injury induced by ethanol in portal hypertensive rats, compared with saline-treated rats. Acute and chronic pretreatment with propranolol had no protective effect in sham-operated rats. In portal hypertensive rats, sucralfate in two different doses (500 and 125 mg/kg) protected the gastric mucosa against ethanol-induced gastric injury compared with animals receiving saline (2 +/- 1% and 3 +/- 2% vs. 25 +/- 3%). Sucralfate at the higher dose did not reduce portal pressure in portal hypertensive rats. We conclude that: (1) chronic portal hypertension increases ethanol-induced gastric damage; (2) acute and chronic propranolol treatment reduces ethanol-induced gastric injury in portal hypertensive rats, probably by decreasing portal hypertension; (3) sucralfate has a cytoprotective effect in portal hypertensive rats without reducing portal pressure. These results suggest a potential application of sucralfate in patients otherwise treated by sclerotherapy. PMID:3693860

  8. Constriction rate variation produced by partial ligation of the portal vein at pre-hepatic portal hypertension induced in rats

    PubMed Central

    RODRIGUES, Daren Athiê Boy; da SILVA, Aline Riquena; SERIGIOLLE, Leonardo Carvalho; FIDALGO, Ramiro de Sousa; FAVERO, Sergio San Gregorio; LEME, Pedro Luiz Squilacci

    2014-01-01

    Background Partial portal vein ligation causes an increase in portal pressure that remains stable even after the appearance of collateral circulation, with functional adaptation to prolonged decrease in portal blood flow. Aim To assess whether different constriction rates produced by partial ligation of the vein interfere with the results of this experimental model in rats. Methods Three groups of five rats each were used; in group 1 (sham-operated), dissection and measurement of portal vein diameters were performed. Portal hypertension was induced by partial portal vein ligation, reducing its size to 0.9 mm in the remaining 10 animals, regardless of the initial diameter of the veins. Five animals with portal hypertension (group 2) underwent reoperation after 15 days and the rats in group 3 after 30 days. The calculation of the constriction rate was performed using a specific mathematical formula (1 - π r 2 / π R2) x 100% and the statistical analysis with the Student t test. Results The initial diameter of the animal's portal vein was 2.06 mm, with an average constriction rate of the 55.88%; although the diameter of the veins and the constriction rate in group 2 were lower than in group 3 (2.06 mm - 55,25% and 2.08 mm - 56.51%, respectively), portal hypertension was induced in all rats and no significant macroscopic differences were found between the animals that were reoperated after 15 days and after 30 days respectively, being the shorter period considered enough for the evaluation. Comparing the initial diameter of the vein and the rate of constriction performed in groups 2 and 3, no statistic significance was found (p>0.05). Conclusion Pre-hepatic portal hypertension in rat can be induced by the reduction of the portal vein diameter to 0.9 mm, regardless the initial diameter of the vein and the vessel constriction rate. PMID:25626939

  9. Establishment of a reversible model of prehepatic portal hypertension in rats

    PubMed Central

    Zhao, Xin; Dou, Jian; Gao, Qing-Jun

    2016-01-01

    The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO2), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. PMID:27446299

  10. Cirrhosis and Portal Hypertension

    MedlinePlus

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  11. Autoradiographic study of the regional distribution of gastric blood flow in portal hypertensive rats

    SciTech Connect

    Geraghty, J.G.; Angerson, W.J.; Carter, D.C. )

    1989-11-01

    This study measures regional gastric blood flow in portal hypertensive rats at three separate periods after portal vein ligation using quantitative autoradiography with 14C-labeled iodoantipyrine. The level of corpus mucosal blood flow was significantly reduced in 3-day portal vein-ligated animals compared with sham-operated control animals (30.4 +/- 2.3 vs. 47.1 +/- 5.6 ml/100 g.min). There was no significant difference in corpus mucosal blood flow between portal vein-ligated and sham-operated animals at 7- and 28-day periods, although the level of perfusion was higher in the 28-day portal vein-ligated group. There was no significant difference in antral mucosal or muscle blood flow between portal hypertensive and control animals at any of the study periods. We conclude that the acute period after portal vein ligation is associated with a reduced corpus mucosal microcirculation but that this effect is not sustained in portal hypertensive animals studied at later intervals after portal vein ligation.

  12. Overproduction of nitric oxide inhibits vascular reactivity in portal hypertensive rats

    PubMed Central

    Li, Xi-Ru; Wu, Jin-Sheng; He, Ze-Sheng; Ma, Qing-Jiu; Gao, De-Ming

    1997-01-01

    AIM: To evaluate the relationship between nitric oxide (NO) and hyperdynamic circulatory status in portal hypertension. METHODS: Twenty male Sprague Dawley rats (weighing 200 ± 20 g) were randomized into two groups: portal hypertension group (n = 12) and sham-operated control group (n = 8). The portal hypertensive model was established by means of graded constriction of the portal vein. The concentrations of nitrite (NO2-) in the portal vein and peripheral blood were measured by fluorometric assay to reflect NO levels. The reactivity of isolated abdominal aortic rings from rats with partial portal vein constriction and controls was determined by assessing response to administration of potassium chloride (KCl) (10–80 mmol/L) and phenylephrine (10-9-10-4 mol/L) with or without preincubation with NO synthase inhibitor Nω-nitro-L-arginine (L-NNA). RESULTS: Serum concentrations of NO2- in the portal vein blood (0.766 ± 0.097 μmol/L) and peripheral blood (0.687 ± 0.092 μmol/L) were elevated in portal hypertensive rats, as compared with the concentrations in controls (0.613 ± 0.084 μmol/L and 0.591 ± 0.045 μmol/L respectively, both P < 0.01). In addition, the rates of NO2- in portal vein blood were markedly higher than those in peripheral blood (P < 0.05) in the portal hypertensive rats. Abdominal aortic rings from rats with portal vein constriction exhibited significantly impaired contractility to phenylephrine and KCl, as compared with the control rats. The EC50 values of KCl were markedly higher in the portal hypertensive rings (26.5 ± 0.9 mmol/L) than in the control rings (22.3 ± 1.7 mmol/L, P < 0.01), as were the EC50 values of phenylephrine (37.2 ± 0.4 nmol/L vs control rings: 28.1 ± 0.2 nmol/L, P < 0.01). After preincubation of rings with L-NNA, the difference in EC50 values between portal hypertensive and control rings was no longer statistically significant for either KCl (20.18 ± 0.8 mmol/L vs 19.4 ± 1.2 mmol/L, P > 0.05) or phenylephrine (22

  13. Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

    PubMed Central

    Eizayaga, Francisco; Scorticati, Camila; Prestifilippo, Juan P; Romay, Salvador; Fernandez, Maria A; Castro, José L; Lemberg, Abraham; Perazzo, Juan C

    2006-01-01

    AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment. PMID:16552803

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

    PubMed Central

    Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

    2009-01-01

    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 sham-operated 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, significantly 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 modifies the normal function in some brain regions. PMID:19533812

  15. Noncirrhotic Portal Hypertension

    PubMed Central

    Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

  16. Pregnancy with Portal Hypertension

    PubMed Central

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  17. Portal hypertensive enteropathy

    PubMed Central

    Mekaroonkamol, Parit; Cohen, Robert; Chawla, Saurabh

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentation and grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed. PMID:25729469

  18. In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

    PubMed

    Bomzon, A; Jacob, G; Lee, S S; Meddings, J

    1991-02-01

    It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. PMID:2040106

  19. Collateral Pathways in Portal Hypertension

    PubMed Central

    Sharma, Malay; Rameshbabu, Chittapuram S.

    2012-01-01

    Presence of portosystemic collateral veins (PSCV) is common in portal hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses exist which exhibit hepatofugal flow. With the development of portal hypertension, transmission of backpressure leads to increased flow in these patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction collateral circulation develops in a hepatopetal direction and portoportal pathways are frequently found. The objective of this review is to illustrate the various PSCV and portoportal collateral vein pathways pertinent to portal hypertension in liver cirrhosis and EHPVO. PMID:25755456

  20. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension

    PubMed Central

    Yu, Qing; Shao, Rong; Qian, Hu Sheng; George, Samuel E.; Rockey, Don C.

    2000-01-01

    Reduced production of nitric oxide (NO) in the cirrhotic liver results from a defect in hepatic endothelial cell nitric oxide synthase (ecNOS) and appears to contribute to the high intrahepatic resistance and portal hypertension typical of cirrhosis. Therefore, we postulated that targeting a heterologous NOS isoform to sinusoidal endothelial cells or other perisinusoidal cells, such as hepatic stellate cells, would counter the defect in NO production and reduce resistance to blood flow. Recombinant adenovirus (Ad) carrying the neuronal NOS gene (nNOS) targeted liver sinusoidal endothelial cells, stellate cells, and hepatocytes more efficiently than the corresponding cells in cirrhotic livers, but transduction rates were substantial even in cirrhotic animals. Expression of nNOS in each liver cell type, whether from normal or injured liver, caused increased NO production and inhibited endothelin-1–induced contractility of perisinusoidal stellate cells. Finally, in 2 different in vivo models of cirrhosis and portal hypertension, transduction of livers with recombinant Ad.nNOS significantly reduced intrahepatic resistance and portal pressure. The data highlight the feasibility of gene transfer to diseased liver and hepatic cells and demonstrate the potential of a novel therapy for portal hypertension caused by cirrhosis. PMID:10727442

  1. Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

    PubMed Central

    Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

    2016-01-01

    AIM: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson’s trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to

  2. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

    PubMed

    Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N

    2001-01-01

    Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were

  3. Radioisotopic flow scanning for portal blood flow and portal hypertension

    SciTech Connect

    Hesdorffer, C.S.; Bezwoda, W.R.; Danilewitz, M.D.; Esser, J.D.; Tobias, M.

    1987-08-01

    The use of a simple, noninvasive, isotope scanning technique for the determination of relative portal blood flow and detection of portal hypertension is described. Using this technique the presence of portal hypertension was demonstrated in seven of nine patients known to have elevated portal venous pressure. By contrast, esophageal varices were demonstrated in only five of these patients, illustrating the potential value of the method. Furthermore, this technique has been adapted to the study of portal blood flow in patients with myeloproliferative disorders with splenomegaly but without disturbances in hepatic architecture. Results demonstrate that the high relative splenic flow resulting from the presence of splenomegaly may in turn be associated with elevated relative portal blood flow and portal hypertension. The theoretic reasons for the development of flow-related portal hypertension and its relationship to splenic blood flow are discussed.

  4. Endoscopic Management of Portal Hypertension

    PubMed Central

    Al-Busafi, Said A.; Ghali, Peter; Wong, Philip; Deschenes, Marc

    2012-01-01

    Cirrhosis is the leading cause of portal hypertension worldwide, with the development of bleeding gastroesophageal varices being one of the most life-threatening consequences. Endoscopy plays an indispensible role in the diagnosis, staging, and prophylactic or active management of varices. With the expected future refinements in endoscopic technology, capsule endoscopy may one day replace traditional gastroscopy as a diagnostic modality, whereas endoscopic ultrasound may more precisely guide interventional therapy for gastric varices. PMID:22830037

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

    PubMed Central

    Licks, Francielli; Hartmann, Renata Minuzzo; Marques, Camila; Schemitt, Elizângela; Colares, Josieli Raskopf; Soares, Mariana do Couto; Reys, Juliana; Fisher, Camila; da Silva, Juliana; Marroni, Norma Possa

    2015-01-01

    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 mL 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 mL) for the same period of time as the PPVL + NAC and SO + NAC group. On the 15th 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 (eNOS), vascular endothelial growth factor (VEGF), and nitrotirosine (NTT) proteins in stomach. We also evaluated eNOS 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 mmHg) (P < 0.001). The same was observed when we compared the eNOS (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 eNOS (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 mmHg) (P < 0.001) when compared to PPVL. The expression of e

  6. [Mexican consensus on portal hypertension].

    PubMed

    Narváez-Rivera, R M; Cortez-Hernández, C A; González-González, J A; Tamayo-de la Cuesta, J L; Zamarripa-Dorsey, F; Torre-Delgadillo, A; Rivera-Ramos, J F J; Vinageras-Barroso, J I; Muneta-Kishigami, J E; Blancas-Valencia, J M; Antonio-Manrique, M; Valdovinos-Andraca, F; Brito-Lugo, P; Hernández-Guerrero, A; Bernal-Reyes, R; Sobrino-Cossío, S; Aceves-Tavares, G R; Huerta-Guerrero, H M; Moreno-Gómez, N; Bosques-Padilla, F J

    2013-01-01

    The aim of the Mexican Consensus on Portal Hypertension was to develop documented guidelines to facilitate clinical practice when dealing with key events of the patient presenting with portal hypertension and variceal bleeding. The panel of experts was made up of Mexican gastroenterologists, hepatologists, and endoscopists, all distinguished professionals. The document analyzes themes of interest in the following modules: preprimary and primary prophylaxis, acute variceal hemorrhage, and secondary prophylaxis. The management of variceal bleeding has improved considerably in recent years. Current information indicates that the general management of the cirrhotic patient presenting with variceal bleeding should be carried out by a multidisciplinary team, with such an approach playing a major role in the final outcome. The combination of drug and endoscopic therapies is recommended for initial management; vasoactive drugs should be started as soon as variceal bleeding is suspected and maintained for 5 days. After the patient is stabilized, urgent diagnostic endoscopy should be carried out by a qualified endoscopist, who then performs the corresponding endoscopic variceal treatment. Antibiotic prophylaxis should be regarded as an integral part of treatment, started upon hospital admittance and continued for 5 days. If there is treatment failure, rescue therapies should be carried out immediately, taking into account that interventional radiology therapies are very effective in controlling refractory variceal bleeding. These guidelines have been developed for the purpose of achieving greater clinical efficacy and are based on the best evidence of portal hypertension that is presently available. PMID:23664429

  7. Reactive Oxygen Species Are Involved in Regulating Hypocontractility of Mesenteric Artery to Norepinephrine in Cirrhotic Rats with Portal Hypertension

    PubMed Central

    Chen, Wei; Liu, De-Jun; Huo, Yan-Miao; Wu, Zhi-Yong; Sun, Yong-Wei

    2014-01-01

    Background: Oxidative stress is involved in the hypocontractility of visceral artery to vasoconstrictors and formation of hyperdynamic circulation in cirrhosis with portal hypertension. In the present study, we investigated the effect of reactive oxygen species (ROS) on the mesenteric artery contractility in CCl4-induced cirrhotic rats, and the roles of G protein-coupled receptors (GPCRs) desensitization and RhoA /Rho associated coiled-coil forming protein kinase (ROCK) pathways. Methods: The mesenteric artery contraction to norepinephrine (NE) was determined by vessel perfusion system following treatments with apocynin, tempol or PEG-catalase. The protein expression of α1 adrenergic receptor, β-arrestin-2, ROCK-1, moesin and p-moesin was measured by western blot. The interaction between α1 adrenergic receptor and β-arrestin-2 was assessed by co-immunoprecipitation. Results: Pretreatment with apocynin or PEG-catalase in cirrhotic rats, the hydrogen peroxide level in the mesenteric arteriole was significantly decreased, and the dose-response curve of mesenteric arteriole to NE moved to the left with EC50 decreased. There was no significant change for the expression of α1 adrenergic receptor. However, the protein expression of β-arrestin-2 and its affinity with α1 adrenergic receptor were significantly decreased. The ROCK-1 activity and anti- Y-27632 inhibition in cirrhotic rats increased significantly with the protein expression unchanged. Such effects were not observed in tempol-treated group. Conclusion: The H2O2 decrease in mesenteric artery from rats with cirrhosis resulted in down regulation of the β-arrestin-2 expression and its binding ability with α1 adrenergic receptor, thereby affecting the agonist-induced ROCK activation and improving the contractile response in blood vessels. PMID:24719556

  8. Portal hypertensive polyps, a new entity?

    PubMed

    Martín Domínguez, Verónica; Díaz Méndez, Ariel; Santander, Cecilio; García-Buey, Luisa

    2016-05-01

    We present a case of a 62 year old woman with history of liver cirrhosis secondary to autoimmune hepatitis, with portal hypertension and coagulopathy. Gastroscopy findings were a polypoid and polylobed lesions in the gastric antrum. These were removed and the pathological study described hyperplastic polyps with edema, vascular congestion and hyperplasia of smooth muscle, corresponding to "portal hypertensive polyps" (PHP). PMID:27188590

  9. Idiopathic noncirrhotic portal hypertension: current perspectives.

    PubMed

    Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d'Amati, Giulia

    2016-01-01

    The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID:27555800

  10. Idiopathic noncirrhotic portal hypertension: current perspectives

    PubMed Central

    Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d’Amati, Giulia

    2016-01-01

    The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. PMID:27555800

  11. Portal hypertension complicating myelofibrosis: reversal following splenectomy.

    PubMed Central

    Lukie, B. E.; Card, R. T.

    1977-01-01

    Portal hypertension occurs in approximately 10% of patients with myelofibrosis. Increased portal blood flow secondary to splenomegaly has been proposed to explain its development. In a 60-year-old woman with proven myelofibrosis of 10 years' duration and gross splenomegaly, portal hypertension developed with esophageal varices and ascites. There was no demonstrable obstruction to portal blood flow. Following splenectomy the ascites and esophageal varices disappeared. Despite the presence of splenic myeloid metaplasia, splenectomy did not impair the patient's hematologic status. Portal hypertension complicating myelofibrosis has a poor prognosis, so careful attention should be given to its detection. Splenectomy may be preferable to portal-systemic shunting in the management of this complication. Images FIG. 1 FIG. 2 PMID:907949

  12. Characteristics of contractile response of isolated portal veins from chronic portal hypertensive rats under altered levels of external K+, Ca2+, and norepinephrine concentrations: a comparison with normal Wistar rats.

    PubMed

    Yoshimura, T; Arita, M; Kobayashi, M

    1988-01-01

    We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl4 (2 mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0 +/- 38.7 mmH2O) than in the control normal Wistar rats (NWR) (102.0 +/- 25.5 mmH2O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K+, Ca2+, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]o (5.4-86.4 mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]o (0.45-5.4 mM), under conditions of 86.4 mM [K]o was significantly larger in PHR than in NWR preparations. However, the Ca2+ sensitivity of both preparations was the same. D-600 (greater than or equal to 0.1 microM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10 microM), the Ca2+ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the alpha 1-adrenoceptor blocker, prazosin (0.1 microM). The alpha 1-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca2+ release and uptake of intracellular Ca2+ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca2+ permeability. The PHR preparations have a higher affinity for external

  13. Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

    PubMed Central

    Lee, Hwajeong; Rehman, Aseeb Ur; Fiel, M. Isabel

    2016-01-01

    Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID:26563701

  14. Portal hypertension: pathophysiology, diagnosis, and treatment.

    PubMed

    Buob, S; Johnston, A N; Webster, C R L

    2011-01-01

    Portal hypertension (PH) is the result of increased vascular resistance in the portal circulation, increased portal venous blood flow, or both. In veterinary medicine, where portal pressure is seldom measured directly, the diagnosis of PH often is inferred from identification of associated complications including multiple acquired portosystemic shunts, ascites, and hepatic encephalopathy. Likewise, treatment of PH primarily is aimed at controlling these complications. The goal of this review is to provide an update on the pathophysiology, diagnosis, and treatment of PH. The review draws from information in the veterinary hepatology literature, reviews, and consensus statements in human hepatology and the literature on experimental models of PH. PMID:21382073

  15. [Idiopathic non-cirrhotic portal hypertension: An update].

    PubMed

    Bissonnette, Julien; Rautou, Pierre-Emmanuel; Valla, Dominique-Charles

    2015-10-01

    Idiopathic non-cirrhotic portal hypertension is an under-estimated cause of portal hypertension. The diagnosis requires the exclusion of cirrhosis, common causes of chronic liver disease and venous obstruction of the portal and hepatic veins. It has been associated with various extra-hepatic conditions that are most frequently immunologic, prothrombotic, hematologic and toxic. The most frequent clinical complications are variceal hemorrhage and portal vein thrombosis. Complications of portal hypertension should be managed as in patients with cirrhosis. PMID:26362514

  16. Liver surgery in cirrhosis and portal hypertension

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

    2016-01-01

    The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis. PMID:26973411

  17. Pancreatic Adenocarcinoma Complicated by Sinistral Portal Hypertension

    PubMed Central

    Kaley, Kristin; Lamb, Lynne

    2016-01-01

    Pancreatic cancer is known for vague symptoms that lead to a delay in diagnosis, and hence most cases are found at an advanced stage. Many complications can happen secondary to pancreatic cancer including diabetes, malabsorption, and deep venous thrombosis. Sinistral (segmental or left-sided) portal hypertension (SPH) refers to portal hypertension confined to the left-sided segment of the portal venous system namely the splenic side, and the most common etiology is splenic vein thrombosis (SVT). We present here a case of a 66-year-old male with advanced pancreatic cancer who died due to bleeding secondary to SVT. We advise physicians caring for these patients to be aware of this complication, which may also be the manifestation of an undiagnosed pancreatic cancer. PMID:27555987

  18. Portal hypertension and ascites in extramedullary hematopoiesis.

    PubMed

    Amarapurkar, Pooja; Parekh, Sunil; Amarapurkar, Anjali; Amarapurkar, Deepak

    2012-06-01

    Myeloproliferative diseases (MPD) are clonal stem cell disorders which mainly include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). They are characterized by leucocytosis, thrombocytosis, erythrocytosis, splenomegaly, and bone marrow hypercellularity. This might also result in extramedullary hematopoiesis. Abdominal manifestation has been recognized as a feature of these disorders. Splenomegaly and hepatomegaly are fairly common as opposed to ascites which is rare. The MPDs mainly affect the hepatic circulatory systems. The common hepatic manifestations are Budd-Chiari syndrome (BCS), portal vein thrombosis (PVT), and nodular regenerative hyperplasia. A few other features seen in MPDs are caused by extramedullary hematopoiesis, increased hepatic blood flow, and secondary hemosiderosis from multiple blood transfusions. Portal hypertension is found in up to 7% of patients. We report a case of portal hypertension with ascites in a patient with extramedullary hematopoiesis treated with transjugular intrahepatic portocaval shunt (TIPS). PMID:25755427

  19. Radioisotopic splenoportography in patients with portal hypertension.

    PubMed

    Samejima, N; Ikeda, K; Yokoyama, Y; Hirata, S

    1989-05-01

    Radio-isotopic splenoportography was performed by injecting 99mTcO4- into the spleens of 46 patients with portal hypertension and 14 patients with various disorders not having portal hypertension. No collateral circulation was demonstrated in the 14 patients without portal hypertension whereas some RI-images of portosystemic collaterals were found in 40 (87.0 per cent) of the 46 patients with portal hypertension. Collaterals were divided into an ascending group and a descending group, the appearance rate of ascending collaterals being 80.4 per cent and that of descending collaterals, 41.3 per cent. There were 3 image patterns in the ascending group, namely, an AZ-pattern in which the azygos vein was demonstrated; a SC-pattern in which the RI-bolus ascended along the esophagus to the neck and the subclavian vein; and an EG-pattern which showed stagnation of the RI-bolus in the esophagogastric region. There were 4 patterns in the descending group, namely; a pattern of gastro-renal caval shunt (GR-pattern); reverse flow patterns into the umbilical or paraumbilical veins (UV-pattern); into the superior mesenteric vein (SMV-pattern); and into the inferior mesenteric vein (IMV-pattern). The appearance of the EG-pattern was seen most frequently (74.4 per cent). The usefulness of this method for surveying the collateral circulation in portal hypertension, estimating the risk of esophageal variceal bleeding and evaluating its treatments, was suggested by the results of this study. PMID:2674500

  20. [Pathophysiology of portal hypertension, what's new?].

    PubMed

    Kim, Moon Young; Baik, Soon Koo

    2010-09-01

    Portal hypertension (PHT) is associated with changes in the intrahepatic, systemic and portosystemic collateral circulations. Alteration in vasoreactivity (vasodilation and vasoconstriction) plays a central role in the pathogenesis of PHT by contributing to increased intrahepatic resistance, hyperdynamic circulation and the expansion of the collateral circulation. PHT is also importantly characterized by changes in vascular structure; termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the sprouting of new blood vessels, also occurs in PHT, especially in the expansion of the portosystemic collateral circulation. These complementary processes of vasoreactivity, vascular remodeling and angiogenesis represent important targets in the research for the treatment of portal hypertension. PMID:20847603

  1. Treatment of ectopic varices with portal hypertension.

    PubMed

    Sato, Takahiro

    2015-06-28

    Ectopic varices are unusual with portal hypertension and can involve any site along the digestive tract outside the gastroesophageal region. Hemorrhage from ectopic varices generally are massive and life threatening. Diagnosis of ectopic varices is difficult and subsequent treatment is also difficult; the optimal treatment has not been established. Recently, interventional radiology and endoscopic treatments have been carried out successfully for hemorrhage from ectopic varices. PMID:26140080

  2. Interventional Radiologic Treatment for Idiopathic Portal Hypertension

    SciTech Connect

    Hirota, Shozo; Ichikawa, Satoshi; Matsumoto, Shinichi; Motohara, Tomofumi; Fukuda, Tetsuya; Yoshikawa, Takeshi

    1999-07-15

    Purpose: To evaluate the usefulness of interventional radiological treatment for idiopathic portal hypertension. Methods: Between 1995 and 1998, we performed an interventional radiological treatment in five patients with idiopathic portal hypertension, four of whom had refused surgery and one of whom had undergone surgery. Three patients with gastroesophageal varices (GEV) were treated by partial splenic embolization (PSE), one patient with esophageal varices (EV) and massive ascites by transjugular intrahepatic portosytemic shunt (TIPS) and PSE, and one patient with GEV by percutaneous transhepatic obliteration (PTO). Midterm results were analyzed in terms of the effect on esophageal and/or gastric varices. Results: In one woman with severe GEV who underwent three sessions of PSE, there was endoscopic confirmation that the GEV had disappeared. In one man his EV shrunk markedly after two sessions of PSE. In two patients slight reduction of the EV was obtained with one application of PSE combined with endoscopic variceal ligation therapy. PTO for GV in one patient resulted in good control of the varices. All patients have survived for 16-42 months since the first interventional treatment, and varices are well controlled. Conclusion: Interventional radiological treatment is effective for patients with idiopathic portal hypertension, whether or not they have undergone surgery.

  3. Capsule Endoscopy for Portal Hypertensive Enteropathy

    PubMed Central

    2016-01-01

    Portal hypertensive enteropathy (PHE) is a mucosal abnormality of the small bowel that is observed in patients with portal hypertension (PH) and can lead to gastrointestinal bleeding and anemia. The pathogenesis is still not completely understood. The introduction of new endoscopic methods, including capsule endoscopy (CE) or balloon-assisted enteroscopy, has increased the detection of these abnormalities. CE can also serve as a road map for deciding subsequent interventions and evaluating the treatment effect. The prevalence of PHE is reportedly 40–70% in patients with PH. Endoscopic findings can be roughly divided into vascular and nonvascular lesions such as inflammatory-like lesions. Traditionally, PHE-associated factors include large esophageal varices, portal hypertensive gastropathy or colopathy, Child-Turcotte-Pugh class B or C, a history of variceal treatment, and acute gastrointestinal bleeding. More recently, on using scoring systems, a high computed tomography or transient elastography score was reportedly PHE-related factors. However, the prevalence of PHE and its related associated factors remain controversial. The management of PHE has not yet been standardized. It should be individualized according to each patient's situation, the availability of therapy, and each institutional expertise. PMID:26819613

  4. Capsule Endoscopy for Portal Hypertensive Enteropathy.

    PubMed

    Jeon, Seong Ran; Kim, Jin-Oh

    2016-01-01

    Portal hypertensive enteropathy (PHE) is a mucosal abnormality of the small bowel that is observed in patients with portal hypertension (PH) and can lead to gastrointestinal bleeding and anemia. The pathogenesis is still not completely understood. The introduction of new endoscopic methods, including capsule endoscopy (CE) or balloon-assisted enteroscopy, has increased the detection of these abnormalities. CE can also serve as a road map for deciding subsequent interventions and evaluating the treatment effect. The prevalence of PHE is reportedly 40-70% in patients with PH. Endoscopic findings can be roughly divided into vascular and nonvascular lesions such as inflammatory-like lesions. Traditionally, PHE-associated factors include large esophageal varices, portal hypertensive gastropathy or colopathy, Child-Turcotte-Pugh class B or C, a history of variceal treatment, and acute gastrointestinal bleeding. More recently, on using scoring systems, a high computed tomography or transient elastography score was reportedly PHE-related factors. However, the prevalence of PHE and its related associated factors remain controversial. The management of PHE has not yet been standardized. It should be individualized according to each patient's situation, the availability of therapy, and each institutional expertise. PMID:26819613

  5. Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt

    PubMed Central

    Deng, Gang; Huang, Xiang-Jun; Luo, Hong-Wu; Huang, Fei-Zhou; Liu, Xun-Yang; Wang, Yong-Heng

    2013-01-01

    AIM: To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride (CCl4). METHODS: Using cre-loxp technique, we created an Ad-myr-HA-Akt virus, in which Akt is labeled by a HA tag and its expression is driven by myr promoter. Further, through measuring enzyme levels and histological structure, we determined the efficacy of this Ad-myr-HA-Akt virus in inhibiting the development of cirrhosis induced by CCl4 in rats. Lastly, using western blotting, we examined the expression levels and/or phosphorylation status of Akt, apoptotic mediators, endothelial nitric oxide synthase (eNOS), and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus. RESULTS: The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment, which was consistent with the sequence reported in the GenBank. The concentrations of Ad-myr-HA-Akt and adenoviral enhanced green fluorescent protein (Ad-EGFP) virus used in the current study were 5.5 × 1011 vp/mL. The portal vein diameter, peak velocity of blood flow, portal blood flow and congestion index were significantly increased in untreated, saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection. In contrast, these parameters in the Akt cirrhosis group were comparable to normal control group. Compared to the normal control, the liver function (Alanine aminotransferase, Aspartate aminotransferase and Albumin) was significantly impaired in the untreated, saline and Ad-EGFP cirrhosis groups. The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated, saline and Ad-EGFP cirrhosis groups. The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups

  6. Portal hypertension as portrayed by marked hepatosplenomegaly: case report

    SciTech Connect

    Greene, R.A.

    1987-12-01

    The liver is vulnerable to as host of disease processes, including portal hypertension. This is a severe hepatic condition in which the liver is subject to numerous imbalances: increased hepatic blood flow, increased portal vein pressure due to extrahepatic portal vein obstruction, and/or increases in hepatic blood flow resistance. Although many diseases states may be responsible for the development of portal hypertension, it is most commonly associated with moderately severe or advanced cirrhosis. Advanced, untreated portal hypertension may cause additional complications such as hepatosplenomegaly, gastrointestinal bleeding, and ascites.

  7. [Pathology of liver cirrhosis and portal hypertension].

    PubMed

    Bläker, H; Theuer, D; Otto, H F

    2001-10-01

    Cirrhosis is a late stage finding in chronic liver diseases of different aetiology. It is defined morphologically as a diffuse process with the presence of fibrosis and structurally abnormal nodules. The consequences of cirrhosis are both, mechanical and functional. The mechanical complications result from intra- and extrahepatic shunting of blood and portal hypertension while the functional relevance bases upon a failure of liver cells to perform their physiological role in metabolism, synthesis and secretion. Beside these complications that are directly linked to liver function cirrhosis in itself is a risk factor for hepatocellular carcinoma. PMID:11715574

  8. [Aspects of pathogenetc pharmacotherapy for portal hypertension in liver cirrhosis].

    PubMed

    Garbuzenko, D V

    2016-01-01

    The review of literature considers the principles of medical treatment for portal hypertension in liver cirrhosis, which are based on the current views of its development mechanisms. It describes both current pharmacotherapy methods for portal hypertension and drugs, the efficacy of which is being investigated. PMID:27135108

  9. Advances in the treatment of portal hypertension in cirrhosis.

    PubMed

    Kimer, N; Wiese, S; Mo, S; Møller, S; Bendtsen, F

    2016-08-01

    Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension. PMID:26982499

  10. [Surgical treatment of portal hypertension: the state of art].

    PubMed

    Shertsinger, A G; Zhigalova, S B; Lebezev, V M; Manukian, G V; Kitsenko, E A

    2013-01-01

    The article highlights modern approaches to the treatment of portal hypertension. The differential tactics is based on the type of portal hypertension, functional liver state, urgency of the situation and severity of blood loss, localization and stage of varices, concomitant diseases, etc. The role of miniinvasive methods is stressed. The reasonability of general treatment algorithm of portal hypertention in specialized centers is proved. PMID:23503380

  11. Amyloidosis: an unusual cause of portal hypertension

    PubMed Central

    Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete e; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

  12. Portal Hypertension as Immune Mediate Disease

    PubMed Central

    Manti, Sara; Marseglia, Lucia; D'Angelo, Gabriella; Filippelli, Martina; Cuppari, Caterina; Gitto, Eloisa; Romano, Claudio; Arrigo, Teresa; Salpietro, Carmelo

    2014-01-01

    Context: Portal Hypertension (PH) is a progressive complication due to chronic liver disease. In addition to pathophysiologic changes in the micro-circulation, in PH are established fibrous tissue (periportal fibrous septal) and regenerative hyperplastic nodules (from micro- to macro-nodules) promoting hepatic architectural distortion. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1981 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the keywords: "portal hypertension, children, immune system, endocrine system, liver fibrosis". Results: It is believed that PH results from three “phenotype”: ischemia-reperfusion, involving nervous system (NS); edema and oxidative damage, involving immune system; inflammation and angiogenesis, involving endocrine system. However, its exact cause still underdiagnosed and unknown. Conclusions: PH is a dynamic and potentially reversible process. Researchers have tried to demonstrate mechanisms underlying PH and its related-complications. This review focuses on the current knowledge regarding the pathogenesis, and immune, endocrine-metabolic factors of disease. The strong positive association between immune system and development of PH could be efficient to identify non-invasive markers of disease, to modify prognosis of PH, and to development and application of specific and individual anti-inflammatory therapy. PMID:24976841

  13. Amyloidosis: an unusual cause of portal hypertension.

    PubMed

    Takayasu, Vilma; Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete E; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

  14. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension

    PubMed Central

    Uschner, Frank E.; Ranabhat, Ganesh; Choi, Steve S.; Granzow, Michaela; Klein, Sabine; Schierwagen, Robert; Raskopf, Esther; Gautsch, Sebastian; van der Ven, Peter F. M.; Fürst, Dieter O.; Strassburg, Christian P.; Sauerbruch, Tilman; Mae Diehl, Anna; Trebicka, Jonel

    2015-01-01

    Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis. PMID:26412302

  15. Management of rectal varices in portal hypertension

    PubMed Central

    Al Khalloufi, Kawtar; Laiyemo, Adeyinka O

    2015-01-01

    Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed. PMID:26730278

  16. Management of rectal varices in portal hypertension.

    PubMed

    Al Khalloufi, Kawtar; Laiyemo, Adeyinka O

    2015-12-28

    Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed. PMID:26730278

  17. Management of portal hypertension derived from uncommon causes

    PubMed Central

    Kim, Sung Hyun; Lee, Hae Min; Lee, Seung Ho; Won, Jong Yoon

    2016-01-01

    Portal hypertension can arise from any condition interfering with normal blood flow at any level within the portal system. Herein, we presented two uncommon cases of the portal hypertension and its treatment with brief literature review. A 71-year-old man who underwent right hemihepatectomy revealed a tumor recurrence adjacent to the inferior vena cava (IVC). After radiofrequency ablation (RFA) with lymph node dissection, he was referred for abdominal distension. The abdomen computed tomography scan showed severe ascites with a narrowing middle hepatic vein (MHV) and IVC around the RFA site. After insertion of two stents at the IVC and MHV, the ascites disappeared. Another 73-year-old man underwent right trisectionectomy of liver and segmental resection of the portal vein (PV). After operation, he underwent conservative management due to continuous abdominal ascites. The abdomen computed tomography scan showed severe ascites with obliteration of the left PV. After insertion of stent, the ascites disappeared. A decrease of the pressure gradient between the PV and IVC is one of the important treatment strategies for portal hypertension. Vascular stent is useful in the reduction of pressure gradient and thus, can be a treatment option for portal hypertension. PMID:27212996

  18. Utility of endoscopic ultrasound in patients with portal hypertension.

    PubMed

    Hammoud, Ghassan M; Ibdah, Jamal A

    2014-10-21

    Endoscopic ultrasound (EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate (Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors and analysis of free abdominal fluid. Using specialized EUS-guided needle biopsy, a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease. EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics, and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt. PMID:25339809

  19. Portal Hypertension Secondary to Spontaneous Arterio-Portal Venous Fistulas: Transcatheter Arterial Embolization with n-Butyl Cyanoacrylate and Microcoils

    SciTech Connect

    Yamagami, Takuji; Nakamura, Toshiyuki; Nishimura, Tsunehiko

    2000-09-15

    We report a 73-year-old man with recurrent variceal bleeding due to portal hypertension caused by multiple intrahepatic arterio-portal venous fistulas, which were successfully occluded by embolization with n-butyl cyanoacrylate and micro-coils.

  20. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

    PubMed

    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation. PMID:26138461

  1. Pharmacologically induced release and modulation of /sup 3/H-norepinephrine (NE) from the isolated portal vein of the spontaneously hypertensive rat (SHR)

    SciTech Connect

    Zhang, S.Q.; Westfall, T.C.

    1986-03-05

    The purpose of the present study was to probe the mechanism for the enhancement of the field-stimulation induced release of /sup 3/H-NE from blood vessels of the SHR compared to normotensive rats. The results of two types of experiments are reported here. First, the effect of nicotine as well as tyramine in inducing the release of /sup 3/H-NE from the superfused portal vein was compared to field stimulation. Secondly, the modulatory effect of serotonin (5-HT) and methacholine (M) on the field stimulation induced release of /sup 3/H-NE was examined. In contrast to the enhancement of the field stimulation induced release of /sup 3/H-NE from the portal vein of the SHR compared to WKY, both nicotine and tyramine produced a similar release of NE from blood vessel obtained from both strains. The fractional release of /sup 3/H-NE to 10/sup -4/, 10/sup -3/ and 10/sup -2/M nicotine was 0.21, 0.67 and 45.5 from WKY and 0.14, 0.68 and 42.4 from SHR. The fractional release of /sup 3/H-NE to 10/sup -4/ and 10/sup -3/M tyramine was 6 and 17 from WKY compared to 7.5 and 17.5 from SHR. The inhibition of /sup 3/H-NE release from the portal vein by both 5-HT and M was similar in blood vessels obtained from SHR and WKY. These results are consistent with there being a defect in the exocytotic induced release of NE from noradrenergic neurons at the vascular neuroeffector junction.

  2. Laparoscopic Cholecystectomy in Patients with Bilharzial Portal Hypertension

    PubMed Central

    Ismail, Abu Azab; Mohamed, Ibnoaf; Suliman, Fedail S

    2000-01-01

    Objective: The purpose of this study was to evaluate the results of laparoscopic cholecystectomy in patients with bilharzial portal hypertension. Methods: Patients who had gallstones and bilharzia had ultrasonographic assessment of peri-portal fibrosis, endoscopy, hemagglutination and rectal snip. Operating time, blood loss, hospital stay, time of return to work and operative mortality were recorded. Follow-up was two weeks, six weeks and six months after discharge. Results: Twenty-five out of 450 patients, who had laparoscopic cholecystectomy, suffered from bilharzial portal hypertension. Ten patients had grade 1 varices, 10 had grade 2 varices, and 5 had grade 3 esophageal varices. All patients had varying degrees of peri-portal fibrosis as shown by ultrasound. Rectal snip showed schistosoma mansoni in 5 patients, and a hemagglutination test was positive in all. Two patients had conversion to open cholecystectomy. Mean operating time was 1 hour and 15 minutes. Average blood loss was 50 cc. Mean hospital stay for 23 patients was 48 hours. Average time of return to work was 2 weeks in 23 patients and 6 weeks in the 2 patients who had conversion. Twenty-two patients benefited from the operation. There was no mortality in this series. Conclusions: Laparoscopic cholecystectomy in patients with bilharzial portal hypertension is feasible and has low morbidity. PMID:10917123

  3. Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

    PubMed Central

    Vujanac, Andreja; Jakovljevic, Vladimir; Djordjevic, Dusica; Zivkovic, Vladimir; Stojkovic, Mirjana; Celikovic, Dragan; Andjelkovic, Nebojsa; Skevin, Aleksandra Jurisic; Djuric, Dragan

    2012-01-01

    AIM: Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O2-), hydrogen peroxide (H2O2), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO2-) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H2O2 decreased at the end of study, probably via O2- mediated disassembling in Haber Weiss and Fenton reaction; O2- increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O2- and H2O2 degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension. PMID:22294839

  4. Portal hypertension associated with primary hypoplasia of the hepatic portal vein in dogs.

    PubMed

    Van den Ingh, T S; Rothuizen, J; Meyer, H P

    1995-10-21

    Portal hypertension caused by primary hypoplasia of the portal vein was diagnosed in 42 dogs. The portal hypertension was manifested by the presence of multiple portosystemic collateral vessels. The main clinical signs were retarded growth or weight loss, apathy, intermittent diarrhoea and vomiting, anorexia, abdominal distension and polydipsia. Major findings at physical examination were ascites in 23 dogs and neurological signs in 16 dogs. The dogs had increased activities of liver enzymes in plasma and increased fasting levels of total bile acids and ammonia; in many of the dogs the packed red cell volume, total serum protein and albumin were low. Gross inspection of the portal vein revealed a patent but underdeveloped extrahepatic vein in 13 of the dogs. Microscopic examination of the liver revealed hypoplasia of the intrahepatic portal veins in all the dogs, and this was associated with minor arteriolar proliferation and absence of fibrosis in 12 of them, with moderate to marked arteriolar proliferation often combined with ductular proliferation in 13, and with marked portal fibrosis (formerly described as hepatoportal fibrosis) with a varying number of arteriolar and bile ductular structures in 17 of the dogs. The disease affected mainly young dogs, and was most likely to have been of congenital origin. PMID:8560700

  5. Portal hypertensive biliopathy: A single center experience and literature review.

    PubMed

    Suárez, Vanessa; Puerta, Andrés; Santos, Luisa Fernanda; Pérez, Juan Manuel; Varón, Adriana; Botero, Rafael Claudino

    2013-03-27

    Portal hypertensive biliopathy (PHB) is characterized by anatomical and functional abnormalities of the intrahepatic, extrahepatic and pancreatic ducts, in patients with portal hypertension associated to extrahepatic portal vein obstruction and less frequently to cirrhosis. These morphological changes, consisting in dilatation and stenosis of the biliary tree, are due to extensive venous collaterals occurring in an attempt to decompress the portal venous blockage. It is usually asymptomatic until it progresses to more advanced stages with cholestasis, jaundice, biliary sludge, gallstones, cholangitis and finally biliary cirrhosis. Imaging modalities of the biliary tree such as Doppler ultrasound, computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are essential to establish the diagnosis and the need of therapeutical interventions. Once the diagnosis is established, treatment with ursodesoxycholic acid seems to be beneficial. Decompression of the biliary tree to dilate, remove stones or implant biliary prosthesis by endoscopic or surgical procedures (hepato-yeyunostomy) usually resolves the cholestatic picture and prevents septic complications. The ideal treatment is the decompression of the portal system, with transjugular intrahepatic porto-systemic shunt or a surgical porto-systemic shunt. Unfortunately, few patients will be candidates for these procedures due to the extension of the thrombotic process. The purpose of this paper is to report the first 3 cases of PHB seen in a Colombian center and to review the literature. PMID:23556047

  6. [Non-cirrhotic portal hypertension with nearly lethal consequences].

    PubMed

    Börner, Nele; Korte, Wolfgang; Doenecke, Christian; Pfister, Maurus; Meyenberger, Christa; Semela, David; Sawatzki, Mikael

    2013-05-22

    We describe the case of a 48-year-old patient presenting with abdominal pain with a history of cerebral ischemia due to a patent foramen ovale with heterozygous factor V mutation. Initial work-up demonstrate a significant thrombosis of the portal venous system combined with signs of portal hypertension (ascites, oesophageal varices). Ultrasound reveals no signs of cirrhosis of the liver. Finally a JAK2 mutation can be detected. Prevention of oesophageal varices is refused. Finally a massive haemorrhage occured. PMID:23692908

  7. Gastrointestinal Bleeding in Cirrhotic Patients with Portal Hypertension

    PubMed Central

    Biecker, Erwin

    2013-01-01

    Gastrointestinal bleeding related to portal hypertension is a serious complication in patients with liver cirrhosis. Most patients bleed from esophageal or gastric varices, but bleeding from ectopic varices or portal hypertensive gastropathy is also possible. The management of acute bleeding has changed over the last years. Patients are managed with a combination of endoscopic and pharmacologic treatment. The endoscopic treatment of choice for esophageal variceal bleeding is variceal band ligation. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the time point of endoscopy. The first-line treatment for primary prophylaxis of esophageal variceal bleeding is nonselective beta blockers. Pharmacologic therapy is recommended for most patients; band ligation is an alternative in patients with contraindications for or intolerability of beta blockers. Treatment options for secondary prophylaxis include variceal band ligation, beta blockers, a combination of nitrates and beta blockers, and combination of band ligation and pharmacologic treatment. A clear superiority of one treatment over the other has not been shown. Bleeding from portal hypertensive gastropathy or ectopic varices is less common. Treatment options include beta blocker therapy, injection therapy, and interventional radiology. PMID:27335828

  8. [Clinical study of radioisotopic splenoportography in portal hypertension].

    PubMed

    Yokoyama, Y

    1990-02-01

    Radioisotopic splenoportography was performed in 55 patients with portal hypertension, in whom 52 had various degrees of esophagogastric varices, and in 20 patients without portal hypertension. In the patients with varices, collateral images were obtained in 50 patients (96%) by this method and no image was obtained in the patients without varices. The rate of positively imaged collaterals was as follows: Esophageal varices 69%, the left gastric vein 85%, the short gastric veins 48%, RI stasis in esophagogastric region 65%, the azygos vein 46%, the subclavian vein 25%, the para-umbilical veins 46%, splenorenal /gastrorenal shunts 19%, the inferior mesenteric vein 17%, the left intercostal veins 6%, and Arantius's duct 4%. These rates were superior to that obtained from the conventional transarterial portography. There were some correlations between RI-images by this method and clinical and laboratory findings; patients with ascending collaterals alone tended to have extensive and severe varices and higher rate of bleeding, on the other hand, variceal bleeding was not found and episodes of portosystemic encephalopathy frequently occurred in patients with descending collaterals alone. After successful sclerotherapy, RI-images of esophageal varices disappeared in 92% of the patients. Radioisotopic splenoportography appears to be a useful diagnostic and follow-up modality for patients with portal hypertension and esophagogastric varices. PMID:2325608

  9. Portal hypertension in kala-azar

    PubMed Central

    Datta, D. V.; Saha, S.; Grover, S. L.; Singh, Samant A.; Chakravarti, R. N.; Chhuttani, P. N.

    1972-01-01

    The present study records haemodynamic studies in three patients with kala-azar, a parasitic disease. All the three patients had high intrasplenic pressure, mild to moderate elevation of wedged hepatic vein pressure, and increased or normal estimated hepatic blood flow. Liver histology showed marked proliferation and swelling of Kupffer cells in the sinusoids. One patient was studied serially for nine months following treatment which showed persistent elevation of intrasplenic pressure though wedge pressure and liver blood flow touched normal levels. Liver biopsy was essentially normal at this stage. These findings may have some relevance to the role of different parasitic infections in the pathogenesis of a heterogeneous group of non-cirrhotic portal fibroses. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 6 PMID:5045707

  10. Variceal bleeding and portal hypertension: new lights on old horizon.

    PubMed

    Bhasin, D K; Siyad, I

    2004-02-01

    New clinical, endoscopic, and imaging modalities for diagnosing varices and predicting bleeding are being investigated. Transnasal endoscopy and ultrathin battery-powered esophagoscopes are being used to improve patient comfort and compliance. Patients who respond to portal pressure-reducing drugs not only have a reduced risk of bleeding, but also a reduced risk of developing other complications, with improved survival. Nitrates have been shown to have no definite role in primary prophylaxis against variceal bleeding. The hemodynamic response to treatment has an independent prognostic value for the risk of variceal bleeding. Newer drugs have been investigated for reducing the hepatic venous pressure gradient, but with little success. Survival after bleeding has increased due to improved patient care and technological advances. Combined radiographic and endoscopic management of gastric varices is evolving and appears to be promising. Nonvariceal bleeding from portal hypertensive gastropathy is increasingly being recognized as a potential cause of bleeding in patients with portal hypertension, and pharmacotherapy with octreotide appears to be promising for the treatment of this condition. Variceal band ligation in children has been found to be as safe and effective as in adults. PMID:14765309

  11. [Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy].

    PubMed

    Goto, Tadahiro; Matsumoto, Ippei; Shinzeki, Makoto; Toyama, Hirochika; Asari, Sadaki; Ueta, Azusa; Ishida, Jun; Nanno, Yoshihide; So, Shinichi; Kinoshita, Hisoka; Matsumoto, Taku; Kuramitsu, Kaori; Tanaka, Motofumi; Takebe, Atsushi; Kido, Masahiro; Ajiki, Tetsuo; Fukumoto, Takumi; Ku, Yonson

    2014-11-01

    Here, we report a case of Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy. A 69-year old man underwent pancreatoduodenectomy for pancreatic cancer in 2006 in which the splenic vein was ligated near the portal vein and then divided. The patient suffered repeated episodes of anemia between 2010 and 2013. However, we could not identify the bleeding site at that time. In 2011, local recurrence was detected. Disease progression occurred despite chemotherapy treatment, which was then discontinued. The left-sided portal hypertension gradually progressed, and the collateral vessels became dilated. In 2014, he was examined in our department for gastrointestinal bleeding. An upper gastrointestinal endoscopy revealed bleeding from gastric varices. Gastrointestinal bleeding ceased after endoscopic injection sclerotherapy ( EIS) was performed; however, the bleeding recurred. Balloon retrograde transvenous occlusion (BRTO) could not be performed because blood flow was not detected within the gastro-renal shunt. An emergency surgery was performed. Surgical splenectomy and devascularization (Hassab's operation) were performed. After surgery, the gastric body varices and gastrointestinal anastomosis disappeared and the bleeding did not occur. He is currently receiving outpatient treatment. PMID:25731474

  12. The Portal Hypertensive Gastropathy: A Case and Review of Literature

    PubMed Central

    Ricci, Lidia; Pelosi, Marcello; Ricci, Serafino

    2016-01-01

    Upper gastrointestinal bleeding is a cause of high risk for morbidity and mortality. It has been debated in alcoholic cirrhosis, if alcohol exerts an exclusive and causal role upon gastropathy or whether it is linked to cirrhotic portal hypertension. The authors describe an autopsy report regarding mortality caused by gastric bleeding in a 53-year-old patient who suffered from cirrhosis. Literature has evidence of direct, marked damage of alcohol upon the gastric mucosa and there is noteworthy statistical data implying the revaluation of the pathogenesis of the bleeding. PMID:27504310

  13. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension.

    PubMed

    Shneider, Benjamin L; Bosch, Jaime; de Franchis, Roberto; Emre, Sukru H; Groszmann, Roberto J; Ling, Simon C; Lorenz, Jonathan M; Squires, Robert H; Superina, Riccardo A; Thompson, Ann E; Mazariegos, George V

    2012-08-01

    Complications of portal hypertension in children lead to significant morbidity and are a leading indication for consideration of liver transplantation. Approaches to the management of sequelae of portal hypertension are well described for adults and evidence-based approaches have been summarized in numerous meta-analyses and conferences. In contrast, there is a paucity of data to guide the management of complications of portal hypertension in children. An international panel of experts was convened on April 8, 2011 at The Children's Hospital of Pittsburgh of UPMC to review and adapt the recent report of the Baveno V Consensus Workshop on the Methodology of Diagnosis and Therapy in Portal Hypertension to the care of children. The opinions of that expert panel are reported. PMID:22409296

  14. Portal hypertension and gastrointestinal bleeding: Diagnosis, prevention and management

    PubMed Central

    Biecker, Erwin

    2013-01-01

    Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed. PMID:23964137

  15. Peliosis hepatis complicated by portal hypertension following renal transplantation.

    PubMed

    Yu, Chia-Ying; Chang, Liang-Che; Chen, Li-Wei; Lee, Tsung-Shih; Chien, Rong-Nan; Hsieh, Ming-Fang; Chiang, Kun-Chun

    2014-03-01

    Peliosis hepatis (PH) is a vascular lesion of the liver that mimics a hepatic tumor. PH is often associated with underlying conditions, such as chronic infection and tumor malignancies, or with the use of anabolic steroids, immunosuppressive drugs, and oral contraceptives. Most patients with PH are asymptomatic, but some present with abdominal distension and pain. In some cases, PH may induce intraperitoneal hemorrhage and portal hypertension. This study analyzed a 46-year-old male who received a transplanted kidney nine years prior and had undergone long-term immunosuppressive therapy following the renal transplantation. The patient experienced progressive abdominal distention and pain in the six months prior to this study. Initially, imaging studies revealed multiple liver tumor-like abnormalities, which were determined to be PH by pathological analysis. Because the hepatic lesions were progressively enlarged, the patient suffered from complications related to portal hypertension, such as intense ascites and esophageal varices bleeding. Although the patient was scheduled to undergo liver transplantation, he suffered hepatic failure and died prior to availability of a donor organ. PMID:24605041

  16. The use of nanoparticles to deliver nitric oxide to hepatic stellate cells for treating liver fibrosis and portal hypertension.

    PubMed

    Duong, Hien T T; Dong, Zhixia; Su, Lin; Boyer, Cyrille; George, Jacob; Davis, Thomas P; Wang, Jianhua

    2015-05-20

    Polymeric nanoparticles are designed to transport and deliver nitric oxide (NO) into hepatic stellate cells (HSCs) for the potential treatment of both liver fibrosis and portal hypertension. The nanoparticles, incorporating NO donor molecules (S-nitrosoglutathione compound), are designed for liver delivery, minimizing systemic delivery of NO. The nanoparticles are decorated with vitamin A to specifically target HSCs. We demonstrate, using in vitro and in vivo experiments, that the targeted nanoparticles are taken up specifically by rat primary HSCs and the human HSC cell line accumulating in the liver. When nanoparticles, coated with vitamin A, release NO in liver cells, we find inhibition of collagen I and α-smooth muscle actin (α-SMA), fibrogenic genes associated with activated HSCs expression in primary rat liver and human activated HSCs without any obvious cytotoxic effects. Finally, NO-releasing nanoparticles targeted with vitamin A not only attenuate endothelin-1 (ET-1) which elicites HSC contraction but also acutely alleviates haemodynamic disorders in bile duct-ligated-induced portal hypertension evidenced by decreasing portal pressure (≈20%) and unchanging mean arterial pressure. This study clearly shows, for the first time, the potential for HSC targeted nanoparticle delivery of NO as a treatment for liver diseases with proven efficacy for alleviating both liver fibrosis and portal hypertension. PMID:25641921

  17. Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients

    PubMed Central

    Wang, Sheng-Lan; Zhu, Xin-Yan; Zhang, Dong-Wei; Zhang, Zhao-Jie; Gao, Heng-Jun; Yang, Chang-Qing

    2015-01-01

    Background: Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. Aims: To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. Methods: 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. Results: The MDA plasma level of cirrhotic patients was significantly higher than the controls (P<0.001) and increased significantly accompanied by the severity of liver fibrosis and portal hypertension (P<0.01). Further, the plasma MDA level of cirrhotic patients was significantly correlated with Child-Pugh classification of cirrhosis (r=0.820, P<0.001), the degree of esophageal varices (r=0.857, P<0.001) and the width of portal vein (r=0.652, P<0.001). The ROC curve analyses showed that the plasma MDA level is a strong predictor of liver cirrhosis and portal hypertension. Conclusions: Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients. PMID:26379897

  18. Spaceflight regulates ryanodine receptor subtype 1 in portal vein myocytes in the opposite way of hypertension.

    PubMed

    Dabertrand, Fabrice; Porte, Yves; Macrez, Nathalie; Morel, Jean-Luc

    2012-02-01

    Gravity has a structural role for living systems. Tissue development, architecture, and organization are modified when the gravity vector is changed. In particular, microgravity induces a redistribution of blood volume and thus pressure in the astronaut body, abolishing an upright blood pressure gradient, inducing orthostatic hypotension. The present study was designed to investigate whether isolated vascular smooth muscle cells are directly sensitive to altered gravitational forces and, second, whether sustained blood pressure changes act on the same molecular target. Exposure to microgravity during 8 days in the International Space Station induced the decrease of ryanodine receptor subtype 1 expression in primary cultured myocytes from rat hepatic portal vein. Identical results were found in portal vein from mice exposed to microgravity during an 8-day shuttle spaceflight. To evaluate the functional consequences of this physiological adaptation, we have compared evoked calcium signals obtained in myocytes from hindlimb unloaded rats, in which the shift of blood pressure mimics the one produced by the microgravity, with those obtained in myocytes from rats injected with antisense oligonucleotide directed against ryanodine receptor subtype 1. In both conditions, calcium signals implicating calcium-induced calcium release were significantly decreased. In contrast, in spontaneous hypertensive rat, an increase in ryanodine receptor subtype 1 expression was observed as well as the calcium-induced calcium release mechanism. Taken together, our results shown that myocytes were directly sensitive to gravity level and that they adapt their calcium signaling pathways to pressure by the regulation of the ryanodine receptor subtype 1 expression. PMID:22096120

  19. Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis

    PubMed Central

    Garbuzenko, Dmitry Victorovich

    2015-01-01

    Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development. PMID:26034348

  20. Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis.

    PubMed

    Garbuzenko, Dmitry Victorovich

    2015-05-28

    Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development. PMID:26034348

  1. Fibronectin as a Prognostic Indicator in Portal Hypertension

    PubMed Central

    Maharaj, D. P.; Garden, O. J.; Carter, D. C.

    1992-01-01

    Plasma fibronectin levels were measured in 33 patients with portal hypertension and c6mpared with modified Child’s grading and a previously described prognostic index. Outcome at one year from blood sampling was recorded. Mean plasma fibronectin level was 304.1 mg/ml (sem 24.3) and significantly lower levels were found in patients who had had a variceal bleed within the previous seven days. Plasma fibronectin levels tended to be lower in patients with poor liver function as assessed by modified Child’s grading but this did not achieve statistical significance. Plasma fibronectin alone was not an accurate predictor of one year survival in these patients but only one of seven patients who had a plasma fibronectin level below 300mg/l in association with a poor prognostic index survived for one year. PMID:1390363

  2. Hepatic Arterioportal Fistula: A Curable Cause of Portal Hypertension in Infancy

    PubMed Central

    Billing, J. S.

    1997-01-01

    Hepatic arterioportal fistulae are a rare cause of portal hypertension. The case is reported of a twoyear old girl with a congenital arterioportal fistula, who presented with splenomegaly and ascites. Colour doppler ultrasound showed a large shunt between the left hepatic artery and a branch of the left portal vein, producing a reversal of flow in the main portal vein. She was treated by a formal left hemihepatectomy, which has been successful in eliminating the fistula and its consequent portal hypertension in the long term. The literature regarding arterioportal fistulae and their treatment is reviewed. PMID:9298386

  3. Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications.

    PubMed

    Siramolpiwat, Sith

    2014-12-01

    Portal hypertension (PH) plays an important role in the natural history of cirrhosis, and is associated with several clinical consequences. The introduction of transjugular intrahepatic portosystemic shunts (TIPS) in the 1980s has been regarded as a major technical advance in the management of the PH-related complications. At present, polytetrafluoroethylene-covered stents are the preferred option over traditional bare metal stents. TIPS is currently indicated as a salvage therapy in patients with bleeding esophageal varices who fail standard treatment. Recently, applying TIPS early (within 72 h after admission) has been shown to be an effective and life-saving treatment in those with high-risk variceal bleeding. In addition, TIPS is recommended as the second-line treatment for secondary prophylaxis. For bleeding gastric varices, applying TIPS was able to achieve hemostasis in more than 90% of patients. More trials are needed to clarify the efficacy of TIPS compared with other treatment modalities, including cyanoacrylate injection and balloon retrograde transvenous obliteration of gastric varices. TIPS should also be considered in bleeding ectopic varices and refractory portal hypertensive gastropathy. In patients with refractory ascites, there is growing evidence that TIPS not only results in better control of ascites, but also improves long-term survival in appropriately selected candidates. In addition, TIPS is a promising treatment for refractory hepatic hydrothorax. However, the role of TIPS in the treatment of hepatorenal and hepatopulmonary syndrome is not well defined. The advantage of TIPS is offset by a risk of developing hepatic encephalopathy, the most relevant post-procedural complication. Emerging data are addressing the determination the optimal time and patient selection for TIPS placement aiming at improving long-term treatment outcome. This review is aimed at summarizing the published data regarding the application of TIPS in the management of

  4. Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications

    PubMed Central

    Siramolpiwat, Sith

    2014-01-01

    Portal hypertension (PH) plays an important role in the natural history of cirrhosis, and is associated with several clinical consequences. The introduction of transjugular intrahepatic portosystemic shunts (TIPS) in the 1980s has been regarded as a major technical advance in the management of the PH-related complications. At present, polytetrafluoroethylene-covered stents are the preferred option over traditional bare metal stents. TIPS is currently indicated as a salvage therapy in patients with bleeding esophageal varices who fail standard treatment. Recently, applying TIPS early (within 72 h after admission) has been shown to be an effective and life-saving treatment in those with high-risk variceal bleeding. In addition, TIPS is recommended as the second-line treatment for secondary prophylaxis. For bleeding gastric varices, applying TIPS was able to achieve hemostasis in more than 90% of patients. More trials are needed to clarify the efficacy of TIPS compared with other treatment modalities, including cyanoacrylate injection and balloon retrograde transvenous obliteration of gastric varices. TIPS should also be considered in bleeding ectopic varices and refractory portal hypertensive gastropathy. In patients with refractory ascites, there is growing evidence that TIPS not only results in better control of ascites, but also improves long-term survival in appropriately selected candidates. In addition, TIPS is a promising treatment for refractory hepatic hydrothorax. However, the role of TIPS in the treatment of hepatorenal and hepatopulmonary syndrome is not well defined. The advantage of TIPS is offset by a risk of developing hepatic encephalopathy, the most relevant post-procedural complication. Emerging data are addressing the determination the optimal time and patient selection for TIPS placement aiming at improving long-term treatment outcome. This review is aimed at summarizing the published data regarding the application of TIPS in the management of

  5. Portosystemic Shunt Surgery in Patients with Idiopathic Noncirrhotic Portal Hypertension.

    PubMed

    Karagul, Servet; Yagci, Mehmet Ali; Tardu, Ali; Ertugrul, Ismail; Kirmizi, Serdar; Sumer, Fatih; Isik, Burak; Kayaalp, Cuneyt; Yilmaz, Sezai

    2016-01-01

    BACKGROUND Idiopathic noncirrhotic portal hypertension (INCPH) is a rare disease characterized by increased portal venous pressure in the absence of cirrhosis and other causes of liver diseases. The aim of the present study was to present our results in using portosystemic shunt surgery in patients with INCPH. MATERIAL AND METHODS Patients who had been referred to our Liver Transplantation Institute for liver transplantation and who had undergone surgery from January 2010 to December 2015 were retrospectively analyzed. Patients with INCPH who had undergone portosystemic shunt procedure were included in the study. Age, sex, symptoms and findings, type of portosystemic shunt, and postoperative complications were assessed. RESULTS A total of 1307 patients underwent liver transplantation from January 2010 to December 2015. Eleven patients with INCPH who did not require liver transplantation were successfully operated on with a portosystemic shunt procedure. The mean follow-up was 30.1±19 months (range 7-69 months). There was no mortality in the perioperative period or during the follow-up. Two patients underwent surgery again due to intra-abdominal hemorrhage; one had bleeding from the surgical site except the portacaval anastomosis and the other had bleeding from the h-graft anastomosis. No patient developed encephalopathy and no patient presented with esophageal variceal bleeding after portosystemic shunt surgery. Shunt thrombosis occurred in 1 patient (9.9%). Only 1 patient developed ascites, which was controlled medically. CONCLUSIONS Portosystemic shunt surgery is a safe and effective procedure for the treatment of patients with INCPH. PMID:27194018

  6. [Are diuretics in the treatment of portal hypertension rational?].

    PubMed

    Reichen, J

    1997-04-01

    When ascites develops in a patient with cirrhosis his probability to survive the following 2 years amounts to 50%. It is determined essentially by the residual functional capacity of the liver. In 80 to 90% of patients ascites due to portal hypertension can be managed by salt restriction and diuretics. Aldosterone-antagonists are more efficient and have fewer side effects than loop diuretics. They may lower portal tension by an additional direct effect on the vasculature. A daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because (prerenal) renal failure may become a threat. If diuretics are insufficient or when a rapid therapeutic success is needed paracentesis of 4-6.1 is a safe option if intravascular volume is substituted simultaneously. Albumin has proven superior to other plasma expanders (protection of renal function, survival). Only in the few patients whose ascites is intractable by the forementioned measures should alternatives such as peritoneo-, venous or porto-systemic shunts (nowadays mostly by interventional techniques via a transjugular catheter) be evaluated. The only treatment which not only attacks ascites symptomatically but also corrects the underlying disease is liver transplantation. PMID:9198853

  7. The use of hemospray in portal hypertensive bleeding; a case series.

    PubMed

    Smith, L A; Morris, A J; Stanley, A J

    2014-02-01

    Hemospray is a haemostatic agent licensed for endoscopic haemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB) in Europe and Canada. Hemospray has been shown to be safe and effective in achieving haemostasis in bleeding peptic ulcers in a prospective clinical study and several further case series have described the use of hemospray in other non-variceal causes of gastrointestinal bleeding. Portal hypertensive gastropathy and colopathy are common in patients with portal hypertension. As hemospray is an easy to apply, non-contact method, which can cover large areas of mucosa, it may be of benefit in acute non-variceal portal hypertensive bleeding. We present data from the first four consecutive patients presenting to our institution with acute haemorrhage secondary to non-variceal diffuse portal hypertensive bleeding treated with hemospray. PMID:24140803

  8. Hepatic Dimethylarginine-Dimethylaminohydrolase1 is Reduced in Cirrhosis and is a Target for Therapy in Portal Hypertension

    PubMed Central

    Mookerjee, Rajeshwar P; Mehta, Gautam; Balasubramaniyan, Vairappan; Mohamed, Fatma; Davies, Nathan; Sharma, Vikram; Iwakiri, Yasuko; Jalan, Rajiv

    2015-01-01

    Background and Aims Portal hypertension is characterized by reduced hepatic eNOS activity. Asymmetric-dimethylarginine (ADMA), an eNOS inhibitor, is elevated in cirrhosis and correlates with severity of portal hypertension. Dimethylargininedimethylaminohydrolase-1 (DDAH-1) is the key enzyme metabolizing hepatic ADMA. This study characterized DDAH-1 in cirrhosis, and explored hepatic DDAH-1 reconstitution through FXR agonism and DDAH-1 gene therapy. Methods DDAH-1 Immunohistochemistry was conducted on human cirrhosis and healthy liver tissue. Subsequently, sham-operated or bile-duct-ligated (BDL) cirrhosis rats were treated with FXR agonist Obeticholic acid (OA, 5mg/kg) or vehicle for 5 days. Further animals underwent hydrodynamic injection with DDAH-1-expressing plasmid or saline control. Groups: Sham+saline, BDL+saline, BDL+DDAH-1-plasmid. Portal pressure (PP) measurements were performed. Plasma ALT was measured by Cobas-Integra; DDAH-1 expression by qPCR and Western blot; eNOS activity by radiometric assay. Results Immunohistochemistry and Western-blotting confirmed hepatic DDAH-1 was restricted to hepatocytes, and expression decreased significantly in cirrhosis. In BDL rats, reduced DDAH-1 expression was associated with elevated hepatic ADMA, reduced eNOS activity and high PP. OA treatment significantly increased DDAH-1 expression, reduced hepatic tissue ADMA, and increased liver NO generation. PP was significantly reduced in BDL+OA vs. BDL+vehicle (8±1 vs. 13.5±0.6 mmHg; p<0.01) with no change in MAP. Similarly, DDAH-1 hydrodynamic injection significantly increased hepatic DDAH-1 gene and protein expression, and significantly reduced PP in BDL+DDAH-1 vs. BDL+ saline (p<0.01). Conclusion This study demonstrates DDAH-1 is a specific molecular target for portal pressure reduction, through actions on ADMA-mediated regulation of eNOS activity. Our data support translational studies targeting DDAH-1 in cirrhosis and portal hypertension. PMID:25152204

  9. Portosystemic shunting in portal hypertension: evaluation with portal scintigraphy with transrectally administered I-123 IMP

    SciTech Connect

    Kashiwagi, T.; Azuma, M.; Ikawa, T.; Takehara, T.; Matsuda, H.; Yoshioka, H.; Mitsutani, N.; Koizumi, T.; Kimura, K.

    1988-10-01

    Portosystemic shunting was evaluated with rectal administration of iodine-123 iodoamphetamine (IMP) in seven patients without liver disease and 53 patients with liver cirrhosis. IMP (2-3 mCi (74-111 MBq)) was administered to the rectum through a catheter. Images of the chest and abdomen were obtained for up to 60 minutes with a scintillation camera interfaced with a computer. In all patients, images of the liver and/or lungs were observed within 5-10 minutes and became clear with time. In patients without liver disease, only liver images could be obtained, whereas the lung was visualized with or without the liver in all patients with liver cirrhosis. The portosystemic shunt index was calculated by dividing counts of lungs by counts of liver and lung. These values were significantly higher in liver cirrhosis, especially in the decompensated stage. Transrectal portal scintigraphy with IMP appears to be a useful method for noninvasive and quantitative evaluation of portosystemic shunting in portal hypertension.

  10. Sinistral Portal Hypertension: Presentation, Radiological Findings, and Treatment Options - A Case Report

    PubMed Central

    Kokabi, Nima; Lee, Edward; Echevarria, Carlos; Loh, Christopher; Kee, Stephen

    2010-01-01

    Sinistral portal hypertension occurs when a pathological process causes occlusion of the splenic vein. The resultant elevated splenic bed venous pressure causes formation of gastric varices which can lead to hematemesis as a common presentation for this disease process. We present a case of sinistral portal hypertension in a patient with acute hematemesis as the primary presentation. Despite the challenging diagnosis process, the patient underwent splenectomy and was managed appropriately according to previously published literature. PMID:22470692

  11. Experimental TIPS with spiral Z-stents in swine with and without induced portal hypertension

    SciTech Connect

    Kichikawa, Kimihiko; Saxon, Richard R.; Nishimine, Kiyoshi; Nishida, Norifumi; Uchida, Barry T.

    1997-05-15

    Purpose. To assess the suitability of spiral Z-stents for transjugular intrahepatic portosystemic shunt (TIPS) and the influence of portal hypertension on shunt patency in young swine. Methods. TIPS were established using spiral Z-stents in 14 domestic swine. In 7 animals, the portal venous pressure was normal; in the other 7, acute portal hypertension was induced by embolization of portal vein branches. Follow-up portal venography and histologic evaluations were done from 1 hr to 12 weeks after TIPS. Results. Follow-up transhepatic portal venograms showed progressive narrowing of the shunt, most priminent in the midportion of the tract. Ingrowth of liver parenchyma between the stent wires found after 3 weeks led to progressive shunt narrowing and shunt occlusion by 12 weeks. A pseudointima grew rapidly inside the stent, peaked in thickness around 4 weeks, and decreased later. Acutely created portal hypertension rapidly returned to normal and there was no difference in TIPS patency between the two groups of animals. Conclusion. Although the spiral Z-stent can be used as a device for creation of TIPS in patients with cirrhotic livers, it is associated with extensive liver ingrowth in swine that leads to rapid shunt occlusion. Portal hypertension was only transient in this model.

  12. Massive bleeding in pregnancy from ruptured oesophageal varices complicating portal hypertension: a cautionary tale

    PubMed Central

    Crocker, Alison; Girling, Joanna; Cotzias, Christina

    2011-01-01

    Portal vein thrombosis (PVT) is a rare complication of pancreatitis and can cause portal hypertension and oesophageal varices. Variceal rupture carries a high mortality. We report a case of successful pregnancy complicated by two episodes of massive variceal bleeding in a woman with PVT, and discuss how this might have been prevented.

  13. von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis

    PubMed Central

    Kalambokis, Georgios N; Baltayiannis, Gerasimos; Christodoulou, Dimitrios

    2016-01-01

    Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi. PMID:27217711

  14. Prevention of Portal Hypertension: from Variceal Development to Clinical Decompensation

    PubMed Central

    Vorobioff, Julio D.; Groszmann, Roberto J

    2015-01-01

    Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastro-esophageal varices related events at different frameworks including prophylactic, emergency or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding and prevent bleeding recurrence, respectively. The objective of pre-primary prophylaxis (PPP) is to avoid variceal development and therefore, it necessarily deals with cirrhotic patients at earlier stages of the disease. At these earlier stages, nonselective beta blocker (NSBB) have been ineffective in preventing the development of varices and other complications of PH. Therefore, treatment should not rely on NSBB. It is possible, that at these earlier stages, etiological treatment of liver disease itself could prevent the progression of PH. This review will focus mainly on early treatment of PH, because if successful, it may translate into histological-hemodynamic improvements, avoiding not only variceal development but also other PH related complications, such as ascites and porto-systemic encephalopathy (PSE). Moreover, the advent of new therapies may allow not only the prevention of the complications of PH, but also the chance of a substantial degree of regression in the cirrhotic process with the possible prevention of hepatocellular carcinoma (HCC). PMID:24913395

  15. Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography.

    PubMed

    Maruyama, Hitoshi; Shiha, Gamal; Yokosuka, Osamu; Kumar, Ashish; Sharma, Barjesh Chander; Ibrahim, Alaa; Saraswat, Vivek; Lesmana, Cosmas Rinaldi A; Omata, Masao

    2016-03-01

    Portal hypertension and hepatic fibrosis are key pathophysiologies with major manifestations in cirrhosis. Although the degree of portal pressure and hepatic fibrosis are pivotal parameters, both are determined using invasive procedures. Ultrasound (US) is a simple and non-invasive technique that is available for use worldwide in the abdominal field. Because of its safety and easy of use, contrast-enhanced US is one of the most frequently used tools in the management of liver tumors for the detection and characterization of lesions, assessment of malignancy grade, and evaluation of therapeutic effects. This wide range of applications drives the practical use of contrast-enhanced US for evaluation of the severity of portal hypertension and hepatic fibrosis. The present article reviews the recent progress in contrast-enhanced US for the assessment of portal hypertension and hepatic fibrosis. PMID:26696585

  16. Current management of the complications of portal hypertension: variceal bleeding and ascites

    PubMed Central

    Dib, Nina; Oberti, Frédéric; Calès, Paul

    2006-01-01

    Portal hypertension is one of the main consequences of cirrhosis. It results from a combination of increased intrahepatic vascular resistance and increased blood flow through the portal venous system. The condition leads to the formation of portosystemic collateral veins. Esophagogastric varices have the greatest clinical impact, with a risk of bleeding as high as 30% within 2 years of medium or large varices developing. Ascites, another important complication of advanced cirrhosis and severe portal hypertension, is sometimes refractory to treatment and is complicated by spontaneous bacterial peritonitis and hepatorenal syndrome. We describe the pathophysiology of portal hypertension and the current management of its complications, with emphasis on the prophylaxis and treatment of variceal bleeding and ascites. PMID:16682712

  17. The Interstitial Lymphatic Peritoneal Mesothelium Axis in Portal Hypertensive Ascites: When in Danger, Go Back to the Sea

    PubMed Central

    Aller, M. A.; Prieto, I.; Argudo, S.; de Vicente, F.; Santamaría, L.; de Miguel, M. P.; Arias, J. L.; Arias, J.

    2010-01-01

    Portal hypertension induces a splanchnic and systemic low-grade inflammatory response that could induce the expression of three phenotypes, named ischemia-reperfusion, leukocytic, and angiogenic phenotypes.During the splanchnic expression of these phenotypes, interstitial edema, increased lymph flow, and lymphangiogenesis are produced in the gastrointestinal tract. Associated liver disease increases intestinal bacterial translocation, splanchnic lymph flow, and induces ascites and hepatorenal syndrome. Extrahepatic cholestasis in the rat allows to study the worsening of the portal hypertensive syndrome when associated with chronic liver disease. The splanchnic interstitium, the mesenteric lymphatics, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of the portal hypertension syndrome complications. The hypothetical comparison between the ascitic and the amniotic fluids allows for translational investigation. From a phylogenetic point of view, the ancestral mechanisms for amniotic fluid production were essential for animal survival out of the aquatic environment. However, their hypothetical appearance in the cirrhotic patient is considered pathological since ultimately they lead to ascites development. But, the adult human being would take advantage of the potential beneficial effects of this “amniotic-like fluid” to manage the interstitial fluids without adverse effects when chronic liver disease aggravates. PMID:21152120

  18. Vascular corrosion casting: analyzing wall shear stress in the portal vein and vascular abnormalities in portal hypertensive and cirrhotic rodents.

    PubMed

    Van Steenkiste, Christophe; Trachet, Bram; Casteleyn, Christophe; van Loo, Denis; Van Hoorebeke, Luc; Segers, Patrick; Geerts, Anja; Van Vlierberghe, Hans; Colle, Isabelle

    2010-11-01

    Vascular corrosion casting is an established method of anatomical preparation that has recently been revived and has proven to be an excellent tool for detailed three-dimensional (3D) morphological examination of normal and pathological microcirculation. In addition, the geometry provided by vascular casts can be further used to calculate wall shear stress (WSS) in a vascular bed using computational techniques. In the first part of this study, the microvascular morphological changes associated with portal hypertension (PHT) and cirrhosis in vascular casts are described. The second part of this study consists of a quantitative analysis of the WSS in the portal vein in casts of different animal models of PHT and cirrhosis using computational fluid dynamics (CFD). Microvascular changes in the splanchnic, hepatic and pulmonary territory of portal hypertensive and cirrhotic mice are described in detail with stereomicroscopic examination and scanning electron microscopy. To our knowledge, our results are the first to report the vascular changes in the common bile duct ligation cirrhotic model. Calculating WSS using CFD methods is a feasible technique in PHT and cirrhosis, enabling the differentiation between different animal models. First, a dimensional analysis was performed, followed by a CFD calculation describing the spatial and temporal WSS distributions in the portal vein. WSS was significantly different between sham/cirrhotic/pure PHT animals with the highest values in the latter. Up till now, no techniques have been developed to quantify WSS in the portal vein in laboratory animals. This study showed for the first time that vascular casting has an important role not only in the morphological evaluation of animal models of PHT and cirrhosis, but also in defining the biological response of the portal vein wall to hemodynamic changes. CFD in 3D geometries can be used to describe the spatial and temporal variations in WSS in the portal vein and to better understand

  19. A rare case report of Solid Pseudopapillary Tumor of the pancreas with portal hypertension

    PubMed Central

    Reddy, Asha; Sanniyasi, Saravanan; George, Dilip Joseph; Narayanan, Cunnigaiper Dhanasekaran

    2016-01-01

    Introduction Solid Pseudopapillary Tumor of the pancreas (SPT) is a rare pancreatic tumor and represents 1–3% of all pancreatic tumors. It usually presents in young females with abdominal pain, nausea, vomiting and abdominal fullness. The first case report was documented in 1959 and since then multiple case reports have been documented on the various surgical approaches for SPT. However, there are not many reported cases where surgery has been performed on SPT with portal hypertension. Presentation of case In our case report, a 19 year old girl presented with a mass in the left side of the abdomen with associated dragging pain. Ultrasound Abdomen and CT (computed tomography) confirmed an SPT with portal hypertension, with the lesion involving the body and tail of pancreas. Discussion Although few reports are available on SPT with portal hypertension, ours is the first report on a benign SPT with sinistral portal hypertension treated with a distal pancreatectomy. The presence of portal hypertension made the excision of the tumor and delineation of the vessels very difficult. However, when great care is taken while handling the dilated vessels, dissection can be completed with minimal blood loss. Conclusion Meticulous surgical technique along with accurate identification of vasculature will aid in the resection. Although some SPTs behave aggressively, most of them are benign and patients with SPT have an excellent prognosis. PMID:27046101

  20. [Liver cirrhosis and portal hypertension: non-invasive measurement of blood flow in the portal vein with Doppler-duplex].

    PubMed

    Fernández, M; Chesta, J; Jirón, M I; Mánquez, P; Brahm, J

    1991-05-01

    Doppler-duplex has been widely used to quantify blood flow. Nevertheless, its usefulness in assessing portal vein flow (PVF) has been questioned due to technical problems: vessel cross sectional area measurements, interobserver variability, and PVF changes related to physiological events. This study was aimed to measure PVF in patients with cirrhosis and portal hypertension, to estimate changes in PVF during the respiratory cycle, and to evaluate intraobserver variability of Doppler-duplex technique. Twenty-two patients with liver cirrhosis and portal hypertension and 22 healthy subjects were included. One operator made 6 measurements of portal vein diameter (D) and mean flow velocity in inspiration and aspiration. Area of the vessel (A) and PVF were calculated by a microprocessor. Interobserver variability was estimated for each subject and a mean was determined for each group. In the control group, PVF was 901 +/- 39 ml/min in inspiration and 633 +/- 38 ml/min in aspiration; p < 0.001. In patients with cirrhosis PVF was 1303 +/- 121 ml/min in inspiration and 1003 +/- 96 ml/min in aspiration; p < 0.001. Intraobserver variability was 6.0 +/- 0.6% for D, 12.0 +/- 3% for MV and 18.3 +/- 1.6% for PVF in healthy subjects and 5.3 +/- 0.7% for D, 9.2 +/- 0.9% for MV and 15.2 +/- 1.5% for PVF in patients with cirrhosis and portal hypertension. In conclusion, PVF is significantly increased in cirrhotics. PVF was higher in inspiration than espiration in both groups. The Doppler-duplex method evaluation of PVF has an important intraobserver variability (18.3 +/- 1.6%). Then, changes in PVF less than 20% are not accurately measured by this technique. PMID:1844290

  1. Culture Model of Rat Portal Myofibroblasts

    PubMed Central

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4–5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  2. Culture Model of Rat Portal Myofibroblasts.

    PubMed

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4-5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  3. Delayed liver laceration following transjugular intrahepatic portosystemic shunt for portal hypertension

    PubMed Central

    Liu, Kai; Fan, Xin-Xin; Wang, Xu-Lin; He, Chang-Sheng; Wu, Xing-Jiang

    2012-01-01

    The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. Delayed liver laceration is a rare complication of the TIPS procedure. We describe a patient with portal hypertension due to liver cirrhosis, who suddenly presented with abdominal hemorrhage and liver laceration 8 d after TIPS. Few reports have described complications after TIPS placement. To the best of our knowledge, this is the first report describing delayed liver laceration. This potential and serious complication appears to be specific and fatal for TIPS in portal hypertension. We advocate careful attention to the technique to avoid this complication, and timely treatment is extremely important. PMID:23326153

  4. Delayed liver laceration following transjugular intrahepatic portosystemic shunt for portal hypertension.

    PubMed

    Liu, Kai; Fan, Xin-Xin; Wang, Xu-Lin; He, Chang-Sheng; Wu, Xing-Jiang

    2012-12-28

    The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. Delayed liver laceration is a rare complication of the TIPS procedure. We describe a patient with portal hypertension due to liver cirrhosis, who suddenly presented with abdominal hemorrhage and liver laceration 8 d after TIPS. Few reports have described complications after TIPS placement. To the best of our knowledge, this is the first report describing delayed liver laceration. This potential and serious complication appears to be specific and fatal for TIPS in portal hypertension. We advocate careful attention to the technique to avoid this complication, and timely treatment is extremely important. PMID:23326153

  5. Nodular regenerative hyperplasia related portal hypertension in a patient with hypogammaglobulinaemia

    PubMed Central

    Lal, Barun Kumar; Stanley, Adrian

    2013-01-01

    Nodular regenerative hyperplasia (NRH) of liver is a relatively rare liver disorder, but a frequent cause of noncirrhotic portal hypertension. We present a lady with common variable immune deficiency who presented with upper gastrointestinal bleeding and deranged liver function tests but preserved synthetic function. Upper gastrointestinal endoscope showed bleeding gastric varices and non-bleeding oesophageal varices. Although her oesophageal varices were eradicated by repeated endoscopic band ligation, the gastric varices failed to resolve after repeated endoscopic histocryl injection and she eventually needed transjugular intrahepatic portosystemic shunt placement. Liver biopsy showed NRH. We review the association of hypogammaglobinaemia and NRH and discuss the appropriate management of portal hypertension in NRH. PMID:23801845

  6. Nodular regenerative hyperplasia related portal hypertension in a patient with hypogammaglobulinaemia.

    PubMed

    Lal, Barun Kumar; Stanley, Adrian

    2013-06-14

    Nodular regenerative hyperplasia (NRH) of liver is a relatively rare liver disorder, but a frequent cause of noncirrhotic portal hypertension. We present a lady with common variable immune deficiency who presented with upper gastrointestinal bleeding and deranged liver function tests but preserved synthetic function. Upper gastrointestinal endoscope showed bleeding gastric varices and non-bleeding oesophageal varices. Although her oesophageal varices were eradicated by repeated endoscopic band ligation, the gastric varices failed to resolve after repeated endoscopic histocryl injection and she eventually needed transjugular intrahepatic portosystemic shunt placement. Liver biopsy showed NRH. We review the association of hypogammaglobinaemia and NRH and discuss the appropriate management of portal hypertension in NRH. PMID:23801845

  7. Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

    PubMed Central

    Gjeorgjievski, Mihajlo; Cappell, Mitchell S

    2016-01-01

    AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: “portal” and “gastropathy”; or “portal” and “hypertensive”; or “congestive” and “gastropathy”; or “congestive” and “gastroenteropathy”. The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa

  8. Impact of obesity and insulin-resistance on cirrhosis and portal hypertension.

    PubMed

    Berzigotti, Annalisa; Abraldes, Juan G

    2013-10-01

    Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article. PMID:23731977

  9. In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats

    PubMed Central

    Van de Casteele, M; Omasta, A; Janssens, S; Roskams, T; Desmet, V; Nevens, F; Fevery, J

    2002-01-01

    Background: Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and decreased activity of hepatic constitutive endothelial nitric oxide synthase (NOS 3) was reported in carbon tetrachloride (CCl4) cirrhotic rat liver. Aims: To study whether an increase in hepatic NOS 3 could be obtained in the CCl4 cirrhotic rat liver by in vivo cDNA transfer and to investigate a possible effect on portal pressure. Methods: Hepatic NOS 3 immunohistochemistry and western blotting were used to measure the amount of NOS 3 protein. Recombinant adenovirus, carrying cDNA encoding human NOS 3, was injected into the portal vein of CCl4 cirrhotic rats. Cirrhotic controls received carrier buffer, naked adenovirus, or adenovirus carrying the lac Z gene. Results: NOS 3 immunoreactivity and amount of protein (western blotting) were significantly decreased in CCl4 cirrhotic livers. Following cDNA transfer, NOS 3 expression and the amount of protein were partially restored. Portal pressure was 11.4 (1.6) mm Hg in untreated cirrhotic (n=9) and 11.8 (0.6) in lac Z transfected (n=4) cirrhotic rats but was reduced to 7.8 (1.0) mm Hg (n=9) five days after NOS 3 cDNA transfer. No changes were observed in systemic haemodynamics, in liver tests or urinary nitrates, or in NOS 3 expression in lung or kidney, indicating a highly selective transfer. Conclusions: NOS 3 cDNA transfer to cirrhotic rat liver is feasible and the increase in hepatic NOS 3 leads to a marked decrease in portal hypertension without systemic effects. These data indicate a major haemodynamic role of intrahepatic NOS 3 in the pathogenesis of portal hypertension in CCl4 cirrhosis. PMID:12171971

  10. Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

    PubMed

    Takuma, Yoshitaka; Nouso, Kazuhiro; Morimoto, Youichi; Tomokuni, Junko; Sahara, Akiko; Takabatake, Hiroyuki; Matsueda, Kazuhiro; Yamamoto, Hiroshi

    2016-05-01

    Purpose To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. Results The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). Conclusion SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis. (©) RSNA

  11. NON-INVASIVE PREDICTORS OF PORTAL HYPERTENSION IN PATIENTS WITH HEPATITIS C VIRUS RELATED HEPATOCELLULAR CARCINOMA.

    PubMed

    Mohran, Zakaria; Sakr, Mohamed; Barakat, Eman; Elbaz, Ahmed; Al-Hamid, Mohamed Abd; Abou-Elmaaty, Mohamed

    2015-12-01

    The reference standard for portal venous pressure measurement which is clinically important for estimating the. feasibility of resection of hepatocellular carcinoma is the hepatic venous pressure gradient, which is, invasive and expqnsive. The present study evaluated the noninvasive parameters for assessment of portal hypertension in Child A patients with hepatocellular carcinoma on top of hepatitis C virus. A total of 112 patients were subjected to clinical assessment, biochemical assay, ultrasonographic Doppler study, triphasic spiral abdominal computed tomography, upper gastrointestinal endoscopy and hepatic venous pressure gradient measurement. According to hepatic venous pressure gradient measurement, they were classified into groups: GI: 58 patients with hepatic venous pressure gradient <10 mmHg and GII: 54 patients with hepatic venous pressure gradient > or = 10 mmHg. Significant variables in univariate analysis were included in a multivariate analysis to establish a model for prediction of clinically significant portal hypertension. Results showed that portal vein diameter > or = 1.3 cm, mono or biphasic pattern of flow in hepatic veins and Giannini index < or = 909 were independent risk factors for the clinically significant portal hypertension as indicated by HVPG > or = 10 mmHg. A model with highest likelihood ratio and good fitness was created. This prediction model was displayed by the receiver operating characteristic curve and under the curve area was 0.969 (0.938-1). PMID:26939231

  12. Prognostic Markers in Patients with Cirrhosis and Portal Hypertension Who Have Not Bled

    PubMed Central

    Poca, Maria; Puente, Angela; Graupera, Isabel; Villanueva, Càndid

    2011-01-01

    Prognostic markers of compensated cirrhosis should mainly investigate factors involved with progression to decompensation because death in cirrhosis is related with decompensation. Portal hypertension plays a crucial role in the pathophysiology of most complications of cirrhosis. Accordingly, HVPGmonitoring has strong prognostic value. An HVPG ≥ 10 mmHg determines a significantly higher risk of developing decompensation. Esophageal varices also can develop when the HVPG is ≥ 10 mmHg, although an HVPG ≥ 12 mmHg is required for variceal bleeding to occur. Monitoring the changes induced by the treatment of portal hypertension on HVPG, provides strong prognostic information. In compensated cirrhosis hemodynamic response is appropriate when the HVPG decreased to <10 mmHg or by > 10% from baseline, because the incidence of complications such as bleeding or ascites significantly decrease when these targets are achieved. Whether serum markers, such as the FibroTest, they, may be valuable to predict decompensation should be established. Transient Elastography is a promising technique that has shown an excellent accuracy to detect severe portal hypertension. However, whether it can adequately determine clinically significant portal hypertension, and risk of developing varices and decompensation, should be established. Magnetic Resonance Elastography is also promising. PMID:22045400

  13. [Esophagogastric devascularization in bleeding esophageal varices due to portal hypertension: median-term results].

    PubMed

    Giordano, G; Angelelli, G; Losacco, T; Mustacchio, N; Macarini, L; Garofalo, G; Petracca, G; Novelli, D; Colelli, P; Cannone, G

    1991-01-01

    The authors report their personal experience in the treatment of bleeding gastroesophageal varices related to portal hypertension. The excellent results of the esophagogastric devascularization observed in the middle-term follow-up (5 years) reinforced authors' opinion on this surgical procedure as the most valid alternative to derivative surgery. Furthermore, they emphasize esophagogastric devascularization can often replace, on principle, derivative surgery. PMID:1751343

  14. Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr

    2011-01-01

    Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH. PMID:21472097

  15. Intraductal ultrasonographic anatomy of biliary varices in patients with portal hypertension

    PubMed Central

    Takagi, Tadayuki; Irisawa, Atsushi; Shibukawa, Goro; Hikichi, Takuto; Obara, Katsutoshi; Ohira, Hiromasa

    2015-01-01

    Background and Objectives: The term, portal biliopathy, denotes various biliary abnormalities, such as stenosis and/or dilatation of the bile duct, in patients with portal hypertension. These vascular abnormalities sometimes bring on an obstructive jaundice, but they are not clear which vessels participated in obstructive jaundice. The aim of present study was clear the bile ductal changes in patients with portal hypertension in hopes of establishing a therapeutic strategy for obstructive jaundice caused by biliary varices. Materials and Methods: Three hundred and thirty-seven patients who underwent intraductal ultrasound (IDUS) during endoscopic retrograde cholangiography for biliary abnormalities were enrolled. Portal biliopathy was analyzed using IDUS. Results: Biliary varices were identified in 11 (2.7%) patients. IDUS revealed biliary varices as multiple, hypoechoic features surrounding the bile duct wall. These varices could be categorized into one of two groups according to their location in the sectional image of bile duct: epicholedochal and paracholedochal. Epicholedochal varices were identified in all patients, but paracholedochal varices were observed only in patients with extrahepatic portal obstruction. Conclusion: IDUS was useful to characterize the anatomy of portal biliopathy in detail. PMID:25789284

  16. Is it time to replace propranolol with carvedilol for portal hypertension?

    PubMed

    Abid, Shahab; Ali, Saadat; Baig, Muhammad Asif; Waheed, Anam Akbar

    2015-05-16

    Beta-adrenergic receptor antagonists (β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol. PMID:25992192

  17. Clinical implication of VEGF serum levels in cirrhotic patients with or without portal hypertension

    PubMed Central

    Nimer, Assy; M, Paizi; D, Gaitini; Y, Baruch; G, Spira

    1999-01-01

    AIM: To determine whether serum vascular endothelial growth factor (VEGF) levels correlates with the severity of liver cirrhosis and whether portal hypertension impacts on the expression of serum VEGF protein. METHODS: Fifty-three patients (mean age 56 ± 2 years) with HCV (n = 26), HBV (n = 13), and cryptogenic liver cirrhosis (n = 14) (Child-Pugh-s class A: 24, B: 19 and C: 12) and normal renal function constitute the patient population, who were all diagnosed by clinical, histological and radiological findings. Six healthy people and six patients with acute hepatitis served as controls. Severity of liver disease was evaluated by the CP score. Serum levels of IGF-1 and VEGF were measured by radioimmunoassay and ELISA, respectively. Portal hypertension was assessed using pulsed Doppler ultrasound. RESULTS: The mean serum VEGF levels in all cirrhotic patients (73 ± 58) were significantly lower than those of healthy controls (360 ± 217, P < 0.01) and acute hepatitis (1123 ± 1261, P < 0.01) respectively. No significant difference in median serum VEGF levels were noted among the different Child-Pugh-s classes (class A: median, 49.4 ng/L, range, 21-260 ng/L, Class B: median 59.9 ng/L; range 21-92, and Class C: median 69; range 20-247 ng/L). A significant correlation was noted between serum VEGF and two accurate parameters of portal hypertension: portal blood flow velocity (r = 06) and spleen size (r = 0.55). No correlation was found between VEGF serum levels and serum albumin, IGF-1, platelets count and aminotrasnferases (r = 0.2, r = 0.1, r = 0.2 and r = 0.2, respectively). CONCLUSION: Circulating VEGF level in patients with liver cirrhosis could not serve as an indicator of the progression of chronic liver disease but rather, they may reflect increased portal hypertension or decreased hepatic regenerative activity or the combination of both. PMID:11819451

  18. Combined transjugular intrahepatic portosystemic shunt and other interventions for hepatocellular carcinoma with portal hypertension

    PubMed Central

    Qiu, Bin; Zhao, Meng-Fei; Yue, Zhen-Dong; Zhao, Hong-Wei; Wang, Lei; Fan, Zhen-Hua; He, Fu-Liang; Dai, Shan; Yao, Jian-Nan; Liu, Fu-Quan

    2015-01-01

    AIM: To evaluate combination transjugular intrahepatic portosystemic shunt (TIPS) and other interventions for hepatocellular carcinoma (HCC) and portal hypertension. METHODS: Two hundred and sixty-one patients with HCC and portal hypertension underwent TIPS combined with other interventional treatments (transarterial chemoembolization/transarterial embolization, radiofrequency ablation, hepatic arterio-portal fistulas embolization, and splenic artery embolization) from January 1997 to January 2010 at Beijing Shijitan Hospital. Two hundred and nine patients (121 male and 88 female, aged 25-69 years, mean 48.3 ± 12.5 years) with complete clinical data were recruited. We evaluated the safety of the procedure (procedure-related death and serious complications), change of portal vein pressure before and after TIPS, symptom relief [e.g., ascites, hydrothorax, esophageal gastric-fundus variceal bleeding (EGVB)], cumulative rates of survival, and distributary channel restenosis. The characteristics of the patients surviving ≥ 5 and < 5 years were also analyzed. RESULTS: The portosystemic pressure was decreased from 29.0 ± 4.1 mmHg before TIPS to 18.1 ± 2.9 mmHg after TIPS (t = 69.32, P < 0.05). Portosystemic pressure was decreased and portal hypertension symptoms were ameliorated. During the 5 year follow-up, the total recurrence rate of resistant ascites or hydrothorax was 7.2% (15/209); 36.8% (77/209) for EGVB; and 39.2% (82/209) for hepatic encephalopathy. The cumulative rates of distributary channel restenosis at 1, 2, 3, 4, and 5 years were 17.2% (36/209), 29.7% (62/209), 36.8% (77/209), 45.5% (95/209) and 58.4% (122/209), respectively. No procedure-related deaths and serious complications (e.g., abdominal bleeding, hepatic failure, and distant metastasis) occurred. Moreover, Child-Pugh score, portal vein tumor thrombosis, lesion diameter, hepatic arterio-portal fistulas, HCC diagnosed before or after TIPS, stent type, hepatic encephalopathy, and type of other

  19. Survival and quality of life after portal blood flow preserving procedures in patients with portal hypertension and liver cirrhosis.

    PubMed

    Orozco, H; Mercado, M A; Takahashi, T; Rojas, G; Hernández, J; Tielve, M

    1994-07-01

    Between 1979 and 1991, 156 patients with histologically proven liver cirrhosis, good liver function, and bleeding portal hypertension underwent operation with portal blood flow preserving procedures (selective shunts: 101; Sugiura-Futagawa: 55). Long-term results of the procedures and the quality of life of the 145 patients who survived the operation were studied. During the observation period (range 3 to 156 months), 28 patients died. The main causes of death were liver failure and hepatoma. Twenty-three patients were lost for follow-up. Twenty-six patients (18%) developed 1 or more encephalopathic episodes. Four patients (3%) experienced rebleeding. One hundred eight patients (74%) had a good quality of life, and 26 (18%) had a poor quality of life. Eleven (15%) of 73 patients with a history of alcoholism continued drinking. Five-year survival for the selective shunt group was 81% and for the devascularization group was 83%. In 81% of the patients, portal blood flow was maintained. It is concluded that both procedures are effective in the long-term. Most patients are able to rehabilitate from the use of alcohol, and most of them have a good quality of life. For patients with good liver function (whose main problem is bleeding), surgery is the best choice of treatment. PMID:8024091

  20. Liver stiffness measurement, better than APRI, Fibroindex, Fib-4, and NBI gastroscopy, predicts portal hypertension in patients with cirrhosis.

    PubMed

    Zhang, Wei; Wang, Liqiong; Wang, Lei; Li, Gang; Huang, Aoshuang; Yin, Ping; Yang, Zhenhua; Ling, Changquan; Wang, Lingtai

    2015-03-01

    Liver stiffness measurement (LSM) is frequently used as non-invasive alternative for liver fibrosis including cirrhosis, which can lead to portal hypertension. This study was conducted to evaluate the predictive value of LSM in cirrhosis-induced portal hypertension patients. Between July 2011 and December 2013, 153 participants were enrolled into a single-center, prospective, cross-sectional study. Each subject received both gastroscopy and LSM. Baseline biochemical, APRI, Fibroindex, and Fib-4 were also performed. LSM of cirrhosis patients with portal hypertension was significantly higher compared to those without portal hypertension (P < 0.05). A LSM ≥ 13.6 kPa had a sensitivity of 83.87 % and a specificity of 72.53 % with an accuracy of 77.1 for the prediction of portal hypertension, which are higher than those of APRI, Fib-4, and Fibroscan separately. A combination of Fibroscan combined with Fib-4 achieved a maximum AUC of 0.833 and accuracy of 77.8. Discriminant and internal validation analysis showed that Fibroscan plus APRI obtained a lower false negative rate compared to Fibroscan plus Fib-4 and Fibroscan plus Fibroindex (9.68, 17.74, and 11.29 %, respectively). A good relationship was found between LSM and NBI mean optical density both by linear and polynomial correlation analysis (r = 0.5533 and r = 0.7349, both P < 0.001). There was a trend toward a better performance of LSM for assessing portal hypertension compared with NBI gastroscopy mean optical density (P = 0.028 and P = 0.05, respectively). Better than APRI, Fibroindex, Fib-4, and NBI gastroscopy, LSM can predict portal hypertension in cirrhosis patients. A LSM of 13.6 kPa can be considered to be the predictive value for portal hypertension. PMID:25417057

  1. Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway.

    PubMed

    Xu, Hong; Zhou, Yang; Lu, Chao; Ping, Jian; Xu, Lie-Ming

    2012-12-01

    The contraction of hepatic stellate cells (HSCs) has a critical role in the regulation of intrahepatic vascular resistance and portal hypertension. Previous studies have confirmed that salvianolic acid B (Sal B) is effective against liver fibrosis. In the present study, we evaluated the effect of Sal B on portal hypertension and on HSCs contractility. Liver cirrhosis was induced in rats by peritoneal injection of dimethylnitrosamine and the portal pressure was measured. HSCs contraction was evaluated by collagen gel contraction assay. Glycerol-urea gel electrophoresis was performed to determine the phosphorylation of myosin light chain 2 (MLC2). F-actin stress fiber polymerization was detected by fluorescein isothiocyanate-labeled phalloidin. Intracellular Ca(2+) and RhoA signaling activation were also measured. Sal B effectively reduced the portal pressure in DMN-induced cirrhotic rats. It decreased the contraction by endothelin-1 (ET-1)-activated HSCs by ∼66.5% and caused the disassembly of actin stress fibers and MLC2 dephosphorylation. Although Sal B reduced ET-1-induced intracellular Ca(2+) increase, blocking Ca(2+) increase completely by BAPTA-AM, a Ca(2+) chelator, barely affected the magnitude of contraction. Sal B decreased ET-1-induced RhoA and Rho-associated coiled coil-forming protein kinase (ROCK) II activation by 66.84% and by 76.79%, respectively, and inhibited Thr(696) phosphorylation of MYPT1 by 80.09%. In vivo, Sal B lowers the portal pressure in rats with DMN-induced cirrhosis. In vitro, Sal B attenuates ET-1-induced HSCs contraction by inhibiting the activation of RhoA and ROCK II and the downstream MYPT1 phosphorylation at Thr(696). We consider Sal B a potential candidate for the pharmacological treatment of portal hypertension. PMID:22986787

  2. Massive duodenal variceal bleed; complication of extra hepatic portal hypertension: Endoscopic management and literature review

    PubMed Central

    Steevens, Christopher; Abdalla, Maisa; Kothari, Truptesh H; Kaul, Vivek; Kothari, Shivangi

    2015-01-01

    Bleeding from duodenal varices is reported to be a catastrophic and often fatal event. Most of the cases in the literature involve patients with underlying cirrhosis. However, approximately one quarter of duodenal variceal bleeds is caused by extrahepatic portal hypertension and they represent a unique population given their lack of liver dysfunction. The authors present a case where a 61-year-old male with history of remote crush injury presented with bright red blood per rectum and was found to have bleeding from massive duodenal varices. Injection sclerotherapy with ethanolamine was performed and the patient experienced a favorable outcome with near resolution of his varices on endoscopic follow-up. The authors conclude that sclerotherapy is a reasonable first line therapy and review the literature surrounding the treatment of duodenal varices secondary to extrahepatic portal hypertension. PMID:26558159

  3. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension.

    PubMed

    Seo, Yeon Seok; Shah, Vijay H

    2012-12-01

    Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension. PMID:23323248

  4. Role of endoscopy in management of gastrointestinal complications of portal hypertension

    PubMed Central

    Luigiano, Carmelo; Iabichino, Giuseppe; Judica, Antonino; Virgilio, Clara; Peta, Valentina; Abenavoli, Ludovico

    2015-01-01

    The management of patients with gastrointestinal complications of portal hypertension is often complex and challenging. The endoscopy plays an important role in the management of these patients. The role of endoscopy is both diagnostic and interventional and in the last years the techniques have undergone a rapid expansion with the advent of different and novel endoscopic modalities, with consequent improvement of investigation and treatment of these patients. The choice of best therapeutic strategy depends on many factors: baseline disease, patient’s clinical performance and the timing when it is done if in emergency or a prophylactic approaches. In this review we evaluate the endoscopic management of patients with the gastrointestinal complications of portal hypertension. PMID:25610530

  5. Emergency cesarean delivery in primigravida with portal hypertension, esophageal varices, and preeclampsia.

    PubMed

    Khanna, Puneet; Garg, Rakesh; Roy, Kajari; Punj, Jyotsna; Pandey, Ravindra; Darlong, Vanlal

    2012-10-01

    The incidence of cirrhosis and advanced portal hypertension during pregnancy is very low, and the literature is scarce with regard to the anesthetic management of a parturient with this coexisting disease. We report the successful perioperative management of a parturi- ent with a history of cirrhosis and portal hypertension with esophageal varices and mild preeclampsia who presented at 38 weeks' gestation in active labor with a breech presentation requiring emergency cesarean delivery. She required endoscopic esophageal varices banding during the second trimester of pregnancy. After correction of her coagulopathy, she was administered subarachnoid block and cesarean delivery, which was conducted uneventfully. Anesthetic management of these patients depends on understanding and avoiding variceal hemorrhage, encephalopathy, renal failure, and careful fluid and electrolyte management. PMID:26050279

  6. Massive duodenal variceal bleed; complication of extra hepatic portal hypertension: Endoscopic management and literature review.

    PubMed

    Steevens, Christopher; Abdalla, Maisa; Kothari, Truptesh H; Kaul, Vivek; Kothari, Shivangi

    2015-11-01

    Bleeding from duodenal varices is reported to be a catastrophic and often fatal event. Most of the cases in the literature involve patients with underlying cirrhosis. However, approximately one quarter of duodenal variceal bleeds is caused by extrahepatic portal hypertension and they represent a unique population given their lack of liver dysfunction. The authors present a case where a 61-year-old male with history of remote crush injury presented with bright red blood per rectum and was found to have bleeding from massive duodenal varices. Injection sclerotherapy with ethanolamine was performed and the patient experienced a favorable outcome with near resolution of his varices on endoscopic follow-up. The authors conclude that sclerotherapy is a reasonable first line therapy and review the literature surrounding the treatment of duodenal varices secondary to extrahepatic portal hypertension. PMID:26558159

  7. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear. PMID:20680541

  8. Hepatic venography in noncirrhotic idiopathic portal hypertension: comparison with cirrhosis of the liver

    SciTech Connect

    Futagawa, S.; Fukazawa, M.; Musha, H.

    1981-11-01

    Free and wedged hepatic venography were carried out in 37 patients with idiopathic portal hypertension (IPH) and the findings compared with those in 88 patients with cirrhosis of the liver. Characteristic changes in IPH included frequent vein-to-vein anastomoses, narrower angles between large veins and their tributaries, smooth and wavy middle-sized to large branches (giving a general ''weeping willow'' appearance), homogeneous sinusoidal filling, and minimal to absent filling of the portal venous system on wedged retrograde portography. In cirrhosis, by contrast, changes included rare vein-to-vein anastomoses, wide angles between veins and tributaries, irregular stenoses of large veins and branches at various levels, spotty sinusoidal filling, and frequent retrograde flow in the portal venous system. Hepatic venography is helpful in differentiating IPH from cirrhosis.

  9. A case of portal hypertension by presumed as plexiform neurofibroma at the hepatic hilum

    PubMed Central

    Lee, Kyung Han; Yoo, Sun Hong; Noh, Gi Tark; Heo, Won Suk; Ko, Byung Seong; Chio, Jung Ah; Cho, Hyo Jin; Choi, Jin Young; Kim, Hee Jun; Sohn, Won; Park, Sang Jong; Park, Young Min

    2016-01-01

    Neurofibromas can occur anywhere in the body, but they usually involve the head, neck, pelvis, and extremities. Abdominal visceral involvement is rare, and intrahepatic involvement is even less common. We describe a patient who suffered from plexiform neurofibromatosis with liver involvement. A 49-year-old man, who had previously been diagnosed with neurofibromatosis, underwent esophagogastroduodenoscopy and abdominal ultrasonography for screening purposes. Esophagogastroduodenoscopy showed grade 2 esophageal varices and abdominal ultrasonography showed conglomerated nodules with echogenic appearances in the perihepatic space. Magnetic resonance imaging showed presumed plexiform neurofibroma involving the lesser sac and hepatic hilum and encasing the common hepatic artery celiac trunk and superior mesenteric artery left portal triad. We report an unusual case of portal hypertension attributed to the compressive narrowing of the portal vein by presumed as plexiform neurofibroma at the lesser sac and hepatic hilum. PMID:27209645

  10. Berry splenic artery aneurysm rupture in association with segmental arterial mediolysis and portal hypertension.

    PubMed

    Imai, Miwa Akasofu; Kawahara, Ei; Katsuda, Shogo; Yamashita, Tatsuya

    2005-05-01

    A rare case of berry splenic artery aneurysm (SAA) rupture associated with segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66-year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6 years earlier, suddenly developed a lancinating pain in the upper abdomen and lost consciousness. She recovered consciousness while being transferred to hospital by ambulance. During the investigations, her level of consciousness suddenly deteriorated. Ultrasonography showed a massive intraperitoneal hemorrhage, and she died 5(1/2) h after admission. On gross examination at autopsy it was not possible to find the rupture point of the vessel because the pancreas was embedded in a massive hematoma. However, careful dissection of the pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in diameter in a branch adjacent to the bifurcation in the distal third of the main splenic artery. Microscopic examination detected a rupture of the aneurysm. The histology of the arterial wall proximal to the aneurysm showed typical SAM. In general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the present case likely occurred and ruptured due to the combination of SAM and portal hypertension. PMID:15871728

  11. Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension

    PubMed Central

    Martins, Cláudio; Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Gamito, Élia; Alves, Ana Luísa; Cremers, Isabelle; Alves, Cecília; Neves, Anabela; Oliveira, Ana Paula

    2016-01-01

    Mastocytosis is a clonal neoplastic disorder of the mast cells (MC) that can be limited to the skin (cutaneous mastocytosis) or involve one or more extracutaneous organs (systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis (ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology. PMID:27605890

  12. Ultrasound-based elastography for the diagnosis of portal hypertension in cirrhotics

    PubMed Central

    Şirli, Roxana; Sporea, Ioan; Popescu, Alina; Dănilă, Mirela

    2015-01-01

    Progressive fibrosis is encountered in almost all chronic liver diseases. Its clinical signs are diagnostic in advanced cirrhosis, but compensated liver cirrhosis is harder to diagnose. Liver biopsy is still considered the reference method for staging the severity of fibrosis, but due to its drawbacks (inter and intra-observer variability, sampling errors, unequal distribution of fibrosis in the liver, and risk of complications and even death), non-invasive methods were developed to assess fibrosis (serologic and elastographic). Elastographic methods can be ultrasound-based or magnetic resonance imaging-based. All ultrasound-based elastographic methods are valuable for the early diagnosis of cirrhosis, especially transient elastography (TE) and acoustic radiation force impulse (ARFI) elastography, which have similar sensitivities and specificities, although ARFI has better feasibility. TE is a promising method for predicting portal hypertension in cirrhotic patients, but it cannot replace upper digestive endoscopy. The diagnostic accuracy of using ARFI in the liver to predict portal hypertension in cirrhotic patients is debatable, with controversial results in published studies. The accuracy of ARFI elastography may be significantly increased if spleen stiffness is assessed, either alone or in combination with liver stiffness and other parameters. Two-dimensional shear-wave elastography, the ElastPQ technique and strain elastography all need to be evaluated as predictors of portal hypertension. PMID:26556985

  13. Splenic Marginal Zone Lymphoma in the Setting of Noncirrhotic Portal Hypertension.

    PubMed

    Ratnayake, Saman; Ammar, Ali; Rezvani, Rodd; Petersen, Greti

    2015-01-01

    We present a case of a 65-year-old Hispanic man with a history of disseminated cutaneous coccidioidomycosis who presented to the emergency room for progressively worsening abdominal pain associated with shortness of breath. The patient was found to have pleural effusion and moderate ascites on physical examination. Abdominal ultrasound and computed tomography scan were consistent with moderate ascites and portal hypertension but negative for both liver cirrhosis and for venous or arterial thrombosis. Cytology of ascitic fluid was suggestive of portal hypertension and was negative for infection. Subsequent, thoracentesis was suggestive of exudative effusion and also negative for infection. Liver biopsy confirmed the absence of cirrhosis. Complete blood count indicated pancytopenia, whereas bone marrow biopsy and flow cytometry were suggestive of marginal zone lymphoma (MZL). Clinically, the patient's shortness of breath was resolved by thoracentesis and paracentesis; however, his abdominal pain persisted. A diagnosis of idiopathic noncirrhotic portal hypertension in the setting of splenic MZL was made. The patient was transferred to a higher level of care for splenectomy; however, he missed multiple appointments. Since discharge, the patient has been seen in the outpatient setting and states that he is controlling his disease with diet and exercise; however, he continues to complain of intermittent shortness of breath with exertion. PMID:26904707

  14. Multiple Giant Splenic Artery Aneurysms Causing Sinistral (Left-Sided) Portal Hypertension

    PubMed Central

    Beksac, Kemal; Karakoc, Derya

    2016-01-01

    Background. Splenic artery aneurysm is the most common type of visceral aneurysms. They are usually asymptomatic and have a potential for rupture and therefore life-threatening hemorrhage. It is rare for them to cause sinistral portal hypertension. Case Report. A 23-year-old female patient presented to our clinic with gastric varices, splenomegaly, pancytopenia, and normal liver functions. She was thus diagnosed with left-sided portal hypertension. Radiologic evaluation showed splenomegaly, splenic vein obstruction, and multiple aneurysms along the splenic artery ranging from 2.5 cm to 7 cm. Splenic artery aneurysm was thought to be the cause of portal hypertension and hypersplenism. We decided splenectomy is the best course of treatment. Pancytopenia could not be corrected preoperatively despite the transfusion treatment. Surgical exploration revealed multiple aneurysms deeply embedded in pancreas. Thrombocyte and erythrocyte transfusion was performed after splenic artery ligation to correct pancytopenia before further intervention. Splenic artery, spleen, and distal pancreas were resected en bloc. Patient's blood parameters became normal within first postoperative day. Patient had an uneventful postoperative course and was discharged without incident. Conclusion. Splenic artery aneurysms are rare but potentially life-threatening incidents. Therefore, it is important to know the unusual presentations and prepare accordingly. PMID:27110411

  15. Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension.

    PubMed

    Martins, Cláudio; Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Gamito, Élia; Alves, Ana Luísa; Cremers, Isabelle; Alves, Cecília; Neves, Anabela; Oliveira, Ana Paula

    2016-07-28

    Mastocytosis is a clonal neoplastic disorder of the mast cells (MC) that can be limited to the skin (cutaneous mastocytosis) or involve one or more extracutaneous organs (systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis (ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology. PMID:27605890

  16. Non-cirrhotic portal hypertension in human immunodeficiency virus-infected patients: a new challenge in antiretroviral therapy era.

    PubMed

    Alvarez Díaz, Hortensia; Mariño Callejo, Ana; García Rodríguez, José Francisco

    2011-01-01

    Non-cirrhotic portal hypertension (NCPH) has been recently reported as a liver disease in Human Immunodeficiency Virus (HIV)-infected patients under antiretroviral therapy (ART). Combination of non-exclusive mechanisms has been described: primary endothelial damage of terminal portal veins induced by HIV or immunologic disorders, mitochondrial toxicity by didanosine and prothrombotic state. It is characterized by heterogeneous liver histological findings, frequently identified as nodular regenerative hyperplasia and clinical manifestations of portal hypertension with well-preserved liver function. We describe herein two HIV-infected patients with clinical picture suggestive of NCPH. Besides the case reports, we briefly address questions to apply to patient care in clinical practice. PMID:21760875

  17. Non-Cirrhotic Portal Hypertension in Human Immunodeficiency Virus-Infected Patients: A New Challenge in Antiretroviral Therapy Era

    PubMed Central

    Álvarez Díaz, Hortensia; Mariño Callejo, Ana; García Rodríguez, José Francisco

    2011-01-01

    Non-cirrhotic portal hypertension (NCPH) has been recently reported as a liver disease in Human Immunodeficiency Virus (HIV)-infected patients under antiretroviral therapy (ART). Combination of non-exclusive mechanisms has been described: primary endothelial damage of terminal portal veins induced by HIV or immunologic disorders, mitochondrial toxicity by didanosine and prothrombotic state. It is characterized by heterogeneous liver histological findings, frequently identified as nodular regenerative hyperplasia and clinical manifestations of portal hypertension with well-preserved liver function. We describe herein two HIV-infected patients with clinical picture suggestive of NCPH. Besides the case reports, we briefly address questions to apply to patient care in clinical practice. PMID:21760875

  18. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

    PubMed Central

    Neves, Rodrigo Vanerson Passos; Souza, Michel Kendy; Passos, Clévia Santos; Bacurau, Reury Frank Pereira; Simoes, Herbert Gustavo; Prestes, Jonato; Boim, Mirian Aparecida; Câmara, Niels Olsen Saraiva; Franco, Maria do Carmo Pinho; Moraes, Milton Rocha

    2016-01-01

    Background Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods Fifteen male SHR [206 ± 10 mmHg of systolic BP (SBP)] and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength. PMID:26840054

  19. INVASIVE AND NON-INVASIVE TECHNIQUES FOR DETECTING PORTAL HYPERTENSION AND PREDICTING VARICEAL BLEEDING IN CIRRHOSIS: A REVIEW

    PubMed Central

    Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J

    2016-01-01

    Portal hypertension is a severe syndrome that may derive from pre-sinusoidal, sinusoidal and post-sinusoidal causes. As a consequence, several complications (i.e., ascites, oesophageal varices) may develop. In sinusoidal portal hypertension, hepatic venous pressure gradient (HVPG) is a reliable method for defining the grade of portal pressure, establishing the effectiveness of the treatment and predicting the occurrence of complications; however, some questions exist regarding its ability to discriminate bleeding from nonbleeding varices in cirrhotic patients. Other imaging techniques (transient elastography, endoscopy, endosonography and duplex Doppler sonography) for assessing causes and complications of portal hypertensive syndrome are available and may be valuable for the management of these patients. In this review, we evaluate invasive and non-invasive techniques currently employed to obtain a clinical prediction of deadly complications, such as variceal bleeding in patients affected by sinusoidal portal hypertension, in order to create a diagnostic algorithm to manage them. Again, HVPG appears to be the reference standard to evaluate portal hypertension and monitor the response to treatment, but its ability to predict several complications and support management decisions might be further improved through the diagnostic combination with other imaging techniques. PMID:24328372

  20. Effects of phased joint intervention on Rho/ROCK expression levels in patients with portal hypertension

    PubMed Central

    Shi, Min; Wei, Jue; Meng, Wen-Ying; Wang, Na; Wang, Ting; Wang, Yu-Gang

    2016-01-01

    The current study investigated the effects of phased joint intervention on clinical efficacy and Rho/Rho-associated coil protein kinase (ROCK) expression in patients with portal hypertension complicated by esophageal variceal bleeding (EVB) and hypersplenism. Patients with portal hypertension (n=53) caused by liver cirrhosis complicated by EVB and hypersplenism treated with phased joint intervention were assessed, and portal hemodynamics, blood, liver function, complications, and rebleeding incidence were analyzed. Reverse transcription-quantitative polymerase chain reaction was used to measure Rho, ROCK1 and ROCK2 mRNA expression levels in peripheral blood mononuclear cells prior to and following phased joint intervention, and western blotting was employed to determine the protein expression levels of Rho, ROCK1, ROCK2, phosphorylated (p) myosin phosphatase target subunit 1 (MYPT1) and total-MYPT1. All patients underwent an emergency assessment of hemostasis with a 100% success rate. Varicose veins were alleviated, and portal hemodynamics and liver function improved following intervention. Furthermore, preoperative and postoperative expression levels of Rho, ROCK1 and ROCK2 mRNA were higher compared with the control group. Notably, the mRNA expression levels of Rho, ROCK1 and ROCK2 in the postoperative group were significantly lower when compared with the preoperative group. Protein expression levels of Rho, ROCK1, ROCK2 and pMYPT1 in the postoperative group were lower, as compared with the preoperative group. Concentration levels of transforming growth factor-β1, connective tissue growth factor and platelet-derived growth factor in peripheral blood were significantly reduced following phased joint intervention. Therefore, the present findings demonstrated that phased joint intervention is able to effectively treat EVB and hypersplenism, and improve liver function. The efficacy of phased joint intervention may be associated with its role in the regulation of the

  1. Diagnostic and Prognostic Values of Noninvasive Predictors of Portal Hypertension in Patients with Alcoholic Cirrhosis

    PubMed Central

    Lee, Il Young; Lim, Yoo Li; Choi, Dae Hee; Kim, Yoon Jun; Yoon, Jung-Hwan; Baik, Soon Koo

    2015-01-01

    Portal hypertension is a direct consequence of hepatic fibrosis, and several hepatic fibrosis markers have been evaluated as a noninvasive alternative to the detection of portal hypertension and esophageal varices. In the present study, we compared the diagnostic and prognostic values of the noninvasive fibrosis markers in patients with alcoholic cirrhosis. A total of 219 consecutive alcoholic cirrhosis patients were included. Biochemical scores and liver stiffness (LS) were compared with hepatic venous pressure gradient (HVPG). For the detection of clinically significant portal hypertension (CSPH; HVPG≥10 mmHg) in compensated patients, LS and LS–spleen diameter to platelet ratio score (LSPS) showed significantly better performance with area under the curves (AUCs) of 0.85 and 0.82, respectively, than aspartate aminotransferase-to-platelet ratio index, FIB-4, Forns’ index, Lok index, (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)], and platelet count-to-spleen diameter ratio (all P<0.001). However, for the detection of high-risk varices, none of the non-invasive tests showed reliable performance (AUCs of all investigated tests < 0.70). During a median follow-up period of 42.6 months, 46 patients with decompensated cirrhosis died. Lok index (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.05–1.22; P = 0.001) and FIB-4 (HR, 1.06; 95% CI, 1.01–1.10; P = 0.009) were independently associated with all-cause death in decompensated patients. Among the tested noninvasive markers, only Lok index significantly improved discrimination function of MELD score in predicting overall survival. In conclusion, LS and LSPS most accurately predict CSPH in patients with compensated alcoholic cirrhosis. In the prediction of overall survival in decompensated patients, however, Lok index is an independent prognostic factor and improves the predictive performance of MELD score. PMID:26196942

  2. Enteroscopic Management of Ectopic Varices in a Patient with Liver Cirrhosis and Portal Hypertension.

    PubMed

    Watson, G A; Abu-Shanab, A; O'Donohoe, R L; Iqbal, M

    2016-01-01

    Portal hypertension and liver cirrhosis may predispose patients to varices, which have a propensity to bleed and cause significant morbidity and mortality. These varices are most commonly located in the gastroesophageal area; however, rarely ectopic varices may develop in unusual locations outside of this region. Haemorrhage from these sites can be massive and difficult to control; thus early detection and management may be lifesaving. We present a case of occult gastrointestinal bleeding in a patient with underlying alcoholic liver disease where an ectopic varix was ultimately detected with push enteroscopy. PMID:27595025

  3. Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

    PubMed Central

    Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor

    2016-01-01

    AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. RESULTS: The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival. PMID:27022226

  4. Enteroscopic Management of Ectopic Varices in a Patient with Liver Cirrhosis and Portal Hypertension

    PubMed Central

    Abu-Shanab, A.

    2016-01-01

    Portal hypertension and liver cirrhosis may predispose patients to varices, which have a propensity to bleed and cause significant morbidity and mortality. These varices are most commonly located in the gastroesophageal area; however, rarely ectopic varices may develop in unusual locations outside of this region. Haemorrhage from these sites can be massive and difficult to control; thus early detection and management may be lifesaving. We present a case of occult gastrointestinal bleeding in a patient with underlying alcoholic liver disease where an ectopic varix was ultimately detected with push enteroscopy. PMID:27595025

  5. Assessment of portal contribution to liver perfusion by quantitative sequential scintigraphy and Doppler ultrasound in alcoholic cirrhosis. Diagnostic value in the detection of portal hypertension.

    PubMed

    Dao, T; Elfadel, S; Bouvard, G; Bouvard, N; Lecointe, I; Jardin-Grimaux, I; Verwaerde, J C; Valla, A

    1993-03-01

    To assess the portal contribution to liver perfusion, we carried out quantitative sequential scintigraphy in 110 patients with alcoholic cirrhosis (22 Child-Pugh class A, 39 class B, 49 class C) and 15 normal subjects. Duplex Doppler ultrasound found a type of intrahepatic circulation that made the standard scintigraphic procedure inaccurate in four cases of cirrhosis, which were reevaluated. Portal contribution to liver perfusion was lower in cirrhotics than in normal subjects (48.7 +/- 29% versus 78.4 +/- 6%; p < 0.001). The sensitivity of scintigraphy in detecting portal hypertension, based on portal contribution < or = 66%, was 61.8% (with a 100% specificity) compared with 66.7% for endoscopy (diagnosis based on existence of varices). The overall sensitivity of the two tests together was 86.1%. Portal contribution to liver perfusion was inversely correlated to Child-Pugh score (r = 0.53; p < 0.001), to prothrombin time (r = 0.52; p < 0.001), and to hepatic venous pressure gradient (r = 0.43; p < 0.001) and positively correlated to albuminemia (r = 0.42; p < 0.001). Concurrent alcoholic hepatitis and the existence of large portosystemic collaterals were related to a decrease in portal contribution to liver perfusion. We conclude that quantitative sequential scintigraphy, which shows a direct relationship between portal contribution to liver perfusion, on the one hand, and the amount of portosystemic shunting, the progression of liver disease, and/or acute liver injury, on the other, could serve as a diagnostic test for portal hypertension. The addition of scintigraphy improves the overall sensitivity of endoscopy. PMID:8463621

  6. Portal hypertension induced by congenital hepatic arterioportal fistula: Report of four clinical cases and review of the literature

    PubMed Central

    Zhang, Dan-Ying; Weng, Shu-Qiang; Dong, Ling; Shen, Xi-Zhong; Qu, Xu-Dong

    2015-01-01

    Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension. PMID:25717263

  7. Evaluation of splenic embolization in patients with portal hypertension and hypersplenism.

    PubMed Central

    Alwmark, A; Bengmark, S; Gullstrand, P; Joelsson, B; Lunderquist, A; Owman, T

    1982-01-01

    Twenty-five patients with hypersplenism caused by portal hypertension were treated by repeated partial splenic embolization. Fourteen surviving patients were followed for up to six years showing a good response on peripheral blood count and bleeding tendency. Three patients died in connection with the treatment and another eight died within half a year because of the underlying liver disease. The discomfort and complications of fever, pain, pleural effusion, and abscess formation and the possibility to avoid these by repeated partial embolization under antibiotic cover are discussed. The results are compared with reports in the reviewed actual literature and the splenic embolization is given a place among the means of a successful selective symptomatic treatment of partial hypertension. PMID:7125739

  8. Establishment and Characterization of Rat Portal Myofibroblast Cell Lines

    PubMed Central

    Fausther, Michel; Goree, Jessica R.; Lavoie, Élise G.; Graham, Alicia L.; Sévigny, Jean; Dranoff, Jonathan A.

    2015-01-01

    The major sources of scar-forming myofibroblasts during liver fibrosis are activated hepatic stellate cells (HSC) and portal fibroblasts (PF). In contrast to well-characterized HSC, PF remain understudied and poorly defined. This is largely due to the facts that isolation of rodent PF for functional studies is technically challenging and that PF cell lines had not been established. To address this, we have generated two polyclonal portal myofibroblast cell lines, RGF and RGF-N2. RGF and RGF-N2 were established from primary PF isolated from adult rat livers that underwent culture activation and subsequent SV40-mediated immortalization. Specifically, Ntpdase2/Cd39l1-sorted primary PF were used to generate the RGF-N2 cell line. Both cell lines were functionally characterized by RT-PCR, immunofluorescence, immunoblot and bromodeoxyuridine-based proliferation assay. First, immortalized RGF and RGF-N2 cells are positive for phenotypic myofibroblast markers alpha smooth muscle actin, type I collagen alpha-1, tissue inhibitor of metalloproteinases-1, PF-specific markers elastin, type XV collagen alpha-1 and Ntpdase2/Cd39l1, and mesenchymal cell marker ecto-5’-nucleotidase/Cd73, while negative for HSC-specific markers desmin and lecithin retinol acyltransferase. Second, both RGF and RGF-N2 cell lines are readily transfectable using standard methods. Finally, RGF and RGF-N2 cells attenuate the growth of Mz-ChA-1 cholangiocarcinoma cells in co-culture, as previously demonstrated for primary PF. Immortalized rat portal myofibroblast RGF and RGF-N2 cell lines express typical markers of activated PF-derived myofibroblasts, are suitable for DNA transfection, and can effectively inhibit cholangiocyte proliferation. Both RGF and RGF-N2 cell lines represent novel in vitro cellular models for the functional studies of portal (myo)fibroblasts and their contribution to the progression of liver fibrosis. PMID:25822334

  9. Hepatic and Splenic Stiffness Augmentation Assessed with MR Elastography in an in vivo Porcine Portal Hypertension Model

    PubMed Central

    Yin, Meng; Kolipaka, Arunark; Woodrum, David A.; Glaser, Kevin J.; Romano, Anthony J; Manduca, Armando; Talwalkar, Jayant A.; Araoz, Philip A.; McGee, Kiaran P.; Anavekar, Nandan S.; Ehman, Richard L.

    2013-01-01

    Purpose To investigate the influence of portal pressure on the shear stiffness of the liver and spleen in a well-controlled in vivo porcine model with MR Elastography (MRE). A significant correlation between portal pressure and tissue stiffness could be used to noninvasively assess increased portal venous pressure (portal hypertension), which is a frequent clinical condition caused by cirrhosis of the liver and is responsible for the development of many lethal complications. Materials and Methods During multiple intra-arterial infusions of Dextran-40 in three adult domestic pigs in vivo, 3-D abdominal MRE was performed with left ventricle and portal catheters measuring blood pressure simultaneously. Least-squares linear regressions were used to analyze the relationship between tissue stiffness and portal pressure. Results Liver and spleen stiffness have a dynamic component that increases significantly following an increase in portal or left ventricular pressure. Correlation coefficients with the linear regressions between stiffness and pressure exceeded 0.8 in most cases. Conclusion The observed stiffness-pressure relationship of the liver and spleen could provide a promising noninvasive method for assessing portal pressure. Using MRE to study the tissue mechanics associated with portal pressure may provide new insights into the natural history and pathophysiology of hepatic diseases and may have significant diagnostic value in the future. PMID:23418135

  10. Transjugular Intrahepatic Portosystemic Shunt Versus Surgical Shunting in the Management of Portal Hypertension

    PubMed Central

    Huang, Long; Yu, Qing-Sheng; Zhang, Qi; Liu, Ju-Da; Wang, Zhen

    2015-01-01

    Background: The purpose of this article was to clarify the optimal management concerning transjugular intrahepatic portosystemic shunts (TIPSs) and surgical shunting in treating portal hypertension. Methods: All databases, including CBM, CNKI, WFPD, Medline, EMBASE, PubMed and Cochrane up to February 2014, were searched for randomized controlled trials (RCTs) comparing TIPS with surgical shunting. Four RCTs, which were extracted by two independent investigators and were evaluated in postoperative complications, mortality, 2- and 5-year survival, hospital stay, operating time and hospitalization charges. Results: The morbidity in variceal rehemorrhage was significantly higher in TIPS than in surgical shunts (odds ratio [OR] = 7.45, 95% confidence interval[CI]: (3.93–14.15), P < 0.00001), the same outcomes were seen in shunt stenosis (OR = 20.01, 95% CI: (6.67–59.99), P < 0.000001) and in hepatic encephalopathy (OR = 2.50, 95% CI: (1.63–3.84), P < 0.0001). Significantly better 2-year survival (OR = 0.66; 95% CI: (0.44–0.98), P = 0.04) and 5-year survival (OR = 0.44; 95% CI: (0.30–0.66), P < 0.00001) were seen in patients undergoing surgical shunting compared with TIPS. Conclusions: Compared with TIPS, postoperative complications and survival after surgical shunting were superior for patients with portal hypertension. Application of surgical shunting was recommended for patients rather than TIPS. PMID:25758281

  11. Management of upper gastrointestinal bleeding from portal hypertension: Elective or emergency operation?

    PubMed Central

    Liu, Sen

    2014-01-01

    Objective: To evaluate the clinical outcome of emergency and elective operation of splenectomy with periesophagogastric devascularization in treating upper gastrointestinal hemorrhage resulted from portal hypertension. Methods: We retrospectively reviewed 219 patients of upper gastrointestinal hemorrhage resulted from portal hypertension treated using emergency or elective operation between Jul 2002 and Aug 2010. The clinical data were collected and analyzed. Results: In the group of elective operation, four patients with grade B and three with grade C died, and in the group of emergency operation, two patients with Grade B and four with Grade C died. The Grade C patients treated using emergency operation presented with a higher mortality than those treated using elective operation, but no significant difference was found (p>0.05). In the two groups, no patients with Grade A died. 17 cases (11.1%) suffered from complications in the group of elective operation and 11 cases (16.7 %) in emergency operation (p>0.05). The complication rate in patients with Grade C is significantly higher than that in patients with Grade A or B in each group (p<0.05). The hospital stay and cost in group of elective operation are significantly higher than those in group of emergency operation (p<0.05). Conclusion: The patients with Grade A or B treated using emergency operation have similar clinical outcomes as those treated using elective operation, but emergency operation may result in higher rate of death and complication in patients with Grade C. PMID:24948982

  12. Noncirrhotic portal hypertension in a human immunodeficiency virus (HIV) infected adolescent

    PubMed Central

    Gouvêa, Aída de Fátima Thomé Barbosa; Machado, Daisy Maria; Beltrão, Suênia Cordeiro de Vasconcelos; do Carmo, Fabiana Bononi; Mattar, Regina Helena Guedes Motta; Succi, Regina Célia de Menezes

    2015-01-01

    OBJECTIVE: To alert the pediatrician who is following up HIV-infected patients about the possibility of non-cirrhotic portal hypertension (NCPH) in this period of life, in order to avoid the catastrophic consequences of this disease as bleeding esophageal varices. CASE DESCRIPTION: A 13 years old HIV-infected patient by vertical route was receiving didanosine (ddI) for 12 years. Although the HIV viral load had been undetectable for 12 years, this patient showed gradual decrease of CD4+ T cells, prolonged thrombocytopenia and high alkaline phosphatase. Physical examination detected splenomegaly, which triggered the investigation that led to the diagnosis of severe liver fibrosis by transient elastography, probably due to hepatic toxicity by prolonged use of ddI. COMMENTS: This is the first case of NCPH in HIV-infected adolescent described in Brazil. Although, the NCPH is a rare disease entity in seropositive patients in the pediatric age group, it should be investigated in patients on long-term ddI or presenting clinical and laboratories indicators of portal hypertension, as splenomegaly, thrombocytopenia and increased alkaline phosphatase. PMID:25913495

  13. Clinical features of patients with Philadelphia-negative myeloproliferative neoplasms complicated by portal hypertension

    PubMed Central

    Yan, Matthew; Geyer, Holly; Mesa, Ruben; Atallah, Ehab; Callum, Jeannie; Bartoszko, Justyna; Yee, Karen; Maganti, Manjula; Wong, Florence; Gupta, Vikas

    2015-01-01

    Backgroud Portal hypertension (PHTN) has been reported to afflict 7-18% of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), with complications of variceal bleeding and ascites. The clinical features and outcomes of these patients are unclear. Patients and Methods In this multi-centre retrospective study, we evaluated the clinical features of 51 patients with MPNs complicated by PHTN. Results The diagnosis of underlying MPN was most frequently polycythemia vera (PV) (39%) and primary myelofibrosis (MF) (35%), followed by post-PV myelofibrosis (18%), essential thrombocythemia (ET) (4%) and post-ET myelofibrosis (4%). Frequency of JAK2 V617F mutation appears as expected in the underlying MPN. Thrombosis within the splanchnic circulation was prevalent in patients with polycythemia compared to other MPNs (76% vs. 26%, p=0.0007). Conclusions PV and MF patients have a higher incidence of PHTN in our population, with thrombosis contributing to PHTN development in PV patients. Patients with splanchnic circulation thrombosis are potential candidates for screening for portal hypertension. These data may be useful for developing screening strategies for early detection of PHTN in patients with MPN. PMID:25027569

  14. Longevity of exercising obese hypertensive rats.

    PubMed

    Booth, F W; MacKenzie, W F; Seider, M J; Gould, E W

    1980-10-01

    The purpose of this study was to determine whether daily running lengthens the life-span of animals dying prematurely due to cardiovascular disease. We used a strain of rat that is genetically hypertensive and obese and is reported to develop atherosclerosis (Exp. Mol. Pathol. 19: 53--60, 1973). These animals were divided into three groups consisting of runners exercised daily on treadmills from an early age life, food-restricted sedentary rats, and libitum eaters that were sedentary. This latter group had significantly higher average daily food intakes and body weights than either of the other two groups. The average life-span of both sedentary groups was significantly longer than the running group. Runners had a greater frequency of focal myocardial necrosis, but atherosclerosis was absent in all three groups. We speculate that daily running may have accentuated the development of factor s that may have contributed to the early death of runners. PMID:7440277

  15. New cellular and molecular targets for the treatment of portal hypertension.

    PubMed

    Gracia-Sancho, Jordi; Maeso-Díaz, Raquel; Fernández-Iglesias, Anabel; Navarro-Zornoza, María; Bosch, Jaime

    2015-04-01

    Portal hypertension (PH) is a common complication of chronic liver disease, and it determines most complications leading to death or liver transplantation in patients with liver cirrhosis. PH results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two mechanisms: (a) distortion of the liver vascular architecture and (b) hepatic microvascular dysfunction. Increment in hepatic resistance is latterly accompanied by splanchnic vasodilation, which further aggravates PH. Hepatic microvascular dysfunction occurs early in the course of chronic liver disease as a consequence of inflammation and oxidative stress and determines loss of the normal phenotype of liver sinusoidal endothelial cells (LSEC). The cross-talk between LSEC and hepatic stellate cells induces activation of the latter, which in turn proliferate, migrate and increase collagen deposition around the sinusoids, contributing to fibrogenesis, architectural disruption and angiogenesis. Therapy for PH aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments, while architectural disruption and fibrosis can be ameliorated by a variety of anti-fibrogenic drugs and anti-angiogenic strategies. Sinusoidal endothelial dysfunction is ameliorated by statins and other drugs increasing NO availability. Splanchnic hyperemia can be counteracted by non-selective beta-blockers (NSBBs), vasopressin analogs and somatostatin analogs. Future treatment of portal hypertension will evolve to use etiological treatments together with anti-fibrotic agents and/or drugs improving microvascular function in initial stages of cirrhosis (pre-primary prophylaxis), while NSBBs will be added in advanced stages of the disease. PMID:25788198

  16. Spatial memory in spontaneously hypertensive rats (SHR).

    PubMed

    Sontag, Thomas-A; Fuermaier, Anselm B M; Hauser, Joachim; Kaunzinger, Ivo; Tucha, Oliver; Lange, Klaus W

    2013-01-01

    The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory. However, the data on spatial working memory deficits in SHRs are not consistent. It has been suggested that the reported cognitive deficits of SHRs may be related to the SHRs' locomotor activity. We have used a holeboard (COGITAT) to study both cognition and activity in order to evaluate the influence of the activity on the cognitive performance of SHRs. In comparison to Wistar-Kyoto (WKY) rats, SHRs did not have any impairment in spatial working memory and reference memory. When the rats' locomotor activity was taken into account, the SHRs' working memory and reference memory were significantly better than in WKY rats. The locomotor activity appears to be a confounding factor in spatial memory tasks and should therefore be controlled for in future studies. In the SHR model of ADHD, we were unable to demonstrate an impairment of working memory which has been reported in patients with ADHD. PMID:24009775

  17. Bone morphogenetic protein receptor 2 in patients with idiopathic portal hypertension

    PubMed Central

    De Gottardi, Andrea; Seijo, Susana; Milá, Montserrat; Alvarez, M Isabel; Bruguera, Miquel; Abraldes, Juan G; Bosch, Jaime; García-Pagán, Juan-Carlos

    2012-01-01

    In idiopathic portal hypertension (IPH) typical vascular lesions are present in the branches of the portal vein or in the perisinusoidal area of the liver. Similar histological alterations have been reported in the pulmonary vasculature of patients with idiopathic pulmonary artery hypertension (IPAH). As IPAH is associated with mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, the aim of this study was to investigate whether this association might also be found in patients with IPH. Twenty-three samples belonging to 21 unrelated caucasian patients with IPH followed in the hepatic haemodynamic laboratory of the Hospital Clinic in Barcelona were included in the study. All patients were studied for the entire open reading frame and splice site of the BMPR2 gene by direct sequencing and multiple ligation probe amplification (MLPA) in order to detect large deletions/duplications. None of the 23 patients had pulmonary artery hypertension. Four patients presented one single nucleotide polymorphism (SNP) in intron 5, four patients had a SNP in exon 12 and a SNP in exon 1 was found in two cases. Two patients had both intron 5 and exon 12 polymorphisms. All SNPs were previously described. Except for these three SNPs, neither mutations nor rearrangements have been identified in the BMPR2 gene in this population. We did not detect mutations or rearrangements in the coding region of the BMPR2 gene in our patients with IPH. These findings suggest that, in contrast to IPAH, mutations in BMPR2 are not involved in the pathogenesis of IPH. PMID:22129439

  18. A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.

    PubMed

    Koot, Bart G P; Alders, Marielle; Verheij, Joanne; Beuers, Ulrich; Cobben, Jan M

    2016-04-01

    Non-cirrhotic portal hypertension is characterized by histopathological abnormalities in the liver, mostly affecting small intrahepatic portal veins that cause portal hypertension in the absence of cirrhosis. It can be secondary to coagulation disorders or toxic agents. However, most cases are idiopathic non-cirrhotic portal hypertension (INCPH) and familial cases are rare. We report a family in which a father and three of his four children conceived with three different mothers are affected by INCPH. Whole exome and Sanger sequencing showed the father to have a de novo single nucleotide substitution c.1348G>C in the KCNN3 gene that was transmitted to all three of his affected offspring. The KCNN3 gene encodes small conductance calcium-activated potassium (SK) channel 3. SK channels are involved in the regulation of arterial and venous vascular tone by causing smooth muscle relaxation on activation. No data exist on the expression and function of SK channels in portal veins. The autosomal dominant inheritance in this unique pedigree and the single de novo mutation identified, strongly suggests that KCNN3 mutations have a pathogenetic role in INCPH. PMID:26658685

  19. Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal Hypertension in an Infant: Uncertainties in the Management and Therapeutic Limitations

    PubMed Central

    Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina

    2016-01-01

    Extrahepatic portal vein obstruction, although rare in children, is a significant cause of portal hypertension (PHT) leading to life-threatening gastrointestinal bleeding in the pediatric age group. PHT may also lead to other complications such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary syndrome and portopulmonary hypertension that may require organ transplantation. Herein we report the case of an asymptomatic 11-month-old infant wherein a hepatomegaly and cavernous transformation of the portal vein was detected by liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor affectation of biliary tract were identified in the magnetic resonance imaging study. A significant enlargement of the caudate lobe of the liver was reported. No risk factors were detected. The differential diagnosis performed was extensive. Inherited thrombophilia and storage disorders were especially considered. Liver biopsy was normal. Upper gastrointestinal esophagogastroduodenoscopy detected two small varicose cords on the distal third of the esophagus. Finding a cavernous transformation of the portal vein with evidence of collateral circulation in such an early age is a challenging condition for professionals, since PHT may lead to severe complications during childhood and can compromise growth and development. Evidence-based guidelines for the management of PHT in adults have been published. However, follow-up and treatment of pediatric patients have not yet been standardized. Moreover, management of PHT in infants faces particular difficulties such as technical restrictions that could hinder their treatment. PMID:27504083

  20. Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy

    PubMed Central

    Marques, Camila; Licks, Francielli; Zattoni, Ingrid; Borges, Beatriz; de Souza, Luiz Eduardo Rizzo; Marroni, Claudio Augusto; Marroni, Norma Possa

    2013-01-01

    AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as

  1. Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

    PubMed Central

    Kim, Jae Hyun; Kim, Jung Min; Cho, Youn Zoo; Na, Ji Hoon; Kim, Hyun Sik; Kim, Hyoun A; Kang, Hye Won; Baik, Soon Koo; Kwon, Sang Ok; Cha, Seung Hwan; Kim, Young Ju

    2014-01-01

    Background/Aims Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. Methods Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. Results The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. Conclusions The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended. PMID:25548744

  2. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats.

    PubMed

    Shimojo, G L; Palma, R K; Brito, J O; Sanches, I C; Irigoyen, M C; De Angelis, K

    2015-06-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation. PMID:25831206

  3. False-positive liver scans due to portal hypertension: correlation with percutaneous transhepatic portograms in 33 patients

    SciTech Connect

    Takayasu, K.; Moriyama, N.; Suzuki, M.; Yamada, T.; Fukutake, T.; Shima, Y.; Kobayashi, C.; Musha, H.; Okuda, K.

    1983-04-01

    Tc-99m-phytate scanning of the liver and percutaneous transhepatic catheterization of the portal vein were performed in 33 patients--26 with cirrhosis, 3 with chronic active hepatitis, 2 with idiopathic portal hypertension, and 2 with unresolved acute hepatitis. A discrete defect in the porta hepatis area was seen in 6 of 28 patients who had portal vein pressure above 200 mm H2O. In 5 of the 6 patients with a false-positive scan, the umbilical portion of the left portal vein branch was dilated (larger than 25 x 20 mm) on the portogram, with or without a patent paraumbilical vein. The anatomical basis of this phenomenon is discussed, and it is suggested that this area be given special attention.

  4. Noncirrhotic portal hypertension in association with juvenile nephropathic cystinosis: case presentation and review of the literature.

    PubMed

    DiDomenico, P; Berry, G; Bass, D; Fridge, J; Sarwal, M

    2004-01-01

    We report a case of portal hypertension and oesophageal varices arising in an 18-year-old female renal transplant recipient with juvenile nephropathic cystinosis diagnosed at 6 years of age. The patient had a history of poor compliance with her prescribed cysteamine therapy. Routine examination revealed normal liver function without hepatomegaly but asymptomatic splenomegaly. An abdominal ultrasound suggested mild oesophageal varices, confirmed later on endoscopy. A liver biopsy revealed an abundance of cystine crystals within the hepatic Kupffer cells, with preserved hepatic architecture. Although the pathophysiology of this rare complication is unclear, in the absence of other aetiologies the likely cause is the patient's poorly controlled cystinosis. As cystinotic patients live longer with improved renal transplant management and cysteamine therapy, it is of interest to characterize the long-term course of the illness after renal transplantation. An understanding of the pathophysiology of hepatic dysfunction will be required to manage this potential late complication of the disease. PMID:15669688

  5. Transjugular intrahepatic porto-systemic shunt in the elderly: Palliation for complications of portal hypertension

    PubMed Central

    Syed, Mubin I; Karsan, Hetal; Ferral, Hector; Shaikh, Azim; Waheed, Uzma; Akhter, Talal; Gabbard, Alan; Morar, Kamal; Tyrrell, Robert

    2012-01-01

    AIM: To present a dedicated series of transjugular intrahepatic porto-systemic shunts (TIPS) in the elderly since data is sparse on this population group. METHODS: A retrospective review was performed of patients at least 65 years of age who underwent TIPS at our institutions between 1997 and 2010. Twenty-five patients were referred for TIPS. We deemed that 2 patients were not considered appropriate candidates due to their markedly advanced liver disease. Of the 23 patients suitable for TIPS, the indications for TIPS placement was portal hypertension complicated by refractory ascites alone (n = 9), hepatic hydrothorax alone (n = 2), refractory ascites and hydrothorax (n = 1), gastrointestinal bleeding alone (n = 8), gastrointestinal bleeding and ascites (n = 3). RESULTS: Of these 23 attempted TIPS procedure patients, 21 patients had technically successful TIPS procedures. A total of 29 out of 32 TIPS procedures including revisions were successful in 21 patients with a mean age of 72.1 years (range 65-82 years). Three of the procedures were unsuccessful attempts at TIPS and 8 procedures were successful revisions of our existing TIPS. Sixteen of 21 patients who underwent successful TIPS (excluding 5 patients lost to follow-up) were followed for a mean of 14.7 mo. Ascites and/or hydrothorax was controlled following technically successful procedures in 12 of 13 patients. Bleeding was controlled following technically successful procedures in 10 out of 11 patients. CONCLUSION: We have demonstrated that TIPS is an effective procedure to control refractory complications of portal hypertension in elderly patients. PMID:22400084

  6. PARATHION TOXICITY IN PERINATAL RATS BORN TO SPONTANEOUSLY HYPERTENSIVE DAMS

    EPA Science Inventory

    Placental transfer and fetal toxicity of pesticides have been documented in normotensive rats but no reports appear in the literature regarding the susceptibility of spontaneously hypertensive (SHR) perinates to pesticide challenge. This report describes the effects of prolonged ...

  7. Hypertension in rats deficient in copper

    SciTech Connect

    Klevay, L.M.

    1986-03-01

    Male weanling rats were matched into two groups of equal mean weight (48 g), were fed a diet low in copper and zinc and were supplemented with a drinking solution with 10..mu..gZn and 2/sup +/gCu per ml until they grew to approximately 300 g. Systolic blood pressure (mmHg) was measured without anesthesia with an Electro-Sphygmomanometer and pneumatic pulse transducer; no significant difference between groups was found (0 > 0.05). Then copper was omitted from the solution of the group with lower blood pressure in each of two experiments. Plasma cholesterol (mg/dl) was measured by fluorometry and blood pressure was measured again 53 to 86 days later; mean (SE), n = 14, 15. Hypercholesterolemia verified deficiency. Hypotension in copper deficient rats in experiments of others probably was the result of cardiac defects induced in weanling animals. Hypertension joins hypercholesterolemia, hyperuricemia, glucose intolerance and abnormal electrocardiograms as a stigma of copper deficiency. Copper deficiency is the only nutritional insult that induces all of these characteristics useful in predicting risk of ischemic heart disease.

  8. Life-Threatening Bleeding from Peristomal Varices after Cystoprostatectomy: Multimodal Approach in a Cirrhotic, Encephalopathic Patient with Severe Portal Hypertension

    PubMed Central

    Staubli, Sergej E. L.; Gramann, Tobias; Schwab, Christoph; Semela, David; Hechelhammer, Lukas; Engeler, Daniel S.; Abt, Dominik; Mordasini, Livio

    2015-01-01

    The bleeding of peristomal varices due to a portosystemic shunt is rare but potentially life-threatening in cirrhotic patients with portal hypertension. The scarce case reports in the literature recommend transjugular intrahepatic portosystemic shunt (TIPS) to prevent further bleeding. We report on a 72-year-old man who was referred to our hospital because of life-threatening bleeding from peristomal varices, three years after radical cystoprostatectomy for invasive bladder cancer. CT imaging showed liver cirrhosis with a prominent portosystemic shunt leading to massively enlarged peristomal varices. TIPS was taken into consideration, but not possible due to hepatic encephalopathy (HE). Medical therapy with lactulose and the nonselective beta-blocker carvedilol was initiated to treat HE and portal hypertension. In a second step, the portosystemic shunt was percutaneously embolized. Here, we present a multimodal approach to treat intractable bleeding from peristomal varices in a patient with ileal conduit urinary diversion, not suitable for TIPS. PMID:25709851

  9. Pleuritic chest pain from portal hypertensive gastropathy in ESRD patient with autosomal dominant polycystic kidney disease misdiagnosed as pericarditis.

    PubMed Central

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma; Achebe, Jennifer; Odenigbo, Charles; Oguejiofor, Fidelis

    2016-01-01

    Portal hypertensive gastropathy (PHG) is a gastric mucosal lesion complicating portal hypertension, with higher prevalence in decompensated cirrhosis. PHG can sometimes complicate autosomal dominant polycystic kidney disease (ADPKD) due to the presence of multiple liver cysts. Besides, PHG is known to present as chest pain, with or without hematemesis. Other causes of chest pain in ADPKD include referred chest pain from progressively enlarging kidney cysts, and rare pericardial cysts. Chest pain, especially if pleuritic, in end-stage renal disease (ESRD) patients, is often ascribed to uremic pericarditis. We present recurrent pleuritic chest pain in a 24-year old ESRD patient with ADPKD that was initially misdiagnosed as uremic pericarditis. It was ultimately shown to represent symptomatic PHG with excellent therapeutic response to proton pump inhibitors. PMID:27069969

  10. Life-threatening bleeding from peristomal varices after cystoprostatectomy: multimodal approach in a cirrhotic, encephalopathic patient with severe portal hypertension.

    PubMed

    Staubli, Sergej E L; Gramann, Tobias; Schwab, Christoph; Semela, David; Hechelhammer, Lukas; Engeler, Daniel S; Schmid, Hans-Peter; Abt, Dominik; Mordasini, Livio

    2015-01-01

    The bleeding of peristomal varices due to a portosystemic shunt is rare but potentially life-threatening in cirrhotic patients with portal hypertension. The scarce case reports in the literature recommend transjugular intrahepatic portosystemic shunt (TIPS) to prevent further bleeding. We report on a 72-year-old man who was referred to our hospital because of life-threatening bleeding from peristomal varices, three years after radical cystoprostatectomy for invasive bladder cancer. CT imaging showed liver cirrhosis with a prominent portosystemic shunt leading to massively enlarged peristomal varices. TIPS was taken into consideration, but not possible due to hepatic encephalopathy (HE). Medical therapy with lactulose and the nonselective beta-blocker carvedilol was initiated to treat HE and portal hypertension. In a second step, the portosystemic shunt was percutaneously embolized. Here, we present a multimodal approach to treat intractable bleeding from peristomal varices in a patient with ileal conduit urinary diversion, not suitable for TIPS. PMID:25709851

  11. Life-threatening hypersplenism due to idiopathic portal hypertension in early childhood: case report and review of the literature

    PubMed Central

    2010-01-01

    Background Idiopathic portal hypertension (IPH) is a disorder of unknown etiology and is characterized clinically by portal hypertension, splenomegaly, and hypersplenism accompanied by pancytopenia. This study evaluates the pathogenic concept of the disease by a systematic review of the literature and illustrates novel pathologic and laboratory findings. Case Presentation We report the first case of uncontrolled splenic hyperperfusion and enlargement with subsequent hypersplenism leading to life-threatening complications of IPH in infancy and emergent splenectomy. Conclusions Our results suggest that splenic NO and VCAM-1, rather than ET-1, have a significant impact on the development of IPH, even at a very early stage of disease. The success of surgical interventions targeting the splenic hyperperfusion suggests that the primary defect in the regulation of splenic blood flow seems to be crucial for the development of IPH. Thus, beside other treatment options splenectomy needs to be considered as a prime therapeutic option for IPH. PMID:20961440

  12. Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats

    PubMed Central

    Nicholas, T. E.

    1971-01-01

    1. The responses of the mean arterial pressure to (—)-noradrenaline, tyramine, angiotensin II-val5-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone. 2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals. 3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade. 4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade. 5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension. 6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension. PMID:4326321

  13. Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)—Newer Insights into Pathogenesis and Emerging Newer Treatment Options

    PubMed Central

    Goel, Ashish; Elias, Joshua E.; Eapen, Chundamannil E.; Ramakrishna, Banumathi; Elias, Elwyn

    2014-01-01

    Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH). Recent data suggest a role for vasoactive factors of portal venous origin in the pathogenesis of this ‘pure’ vasculopathy of the liver. Enteropathies (often silent), are an important ‘driver’ of this disease. NCIPH is under-recognized and often mis-labeled as cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In these patients, with advancing disease and increased porto-systemic shunting, the portal venous vasoactive factors bypass the liver filter and contribute to the development of pulmonary vascular endothelial disorders—porto-pulmonary hypertension and hepato-pulmonary syndrome as well as mesangiocapillary glomerulonephritis. Prognosis in NCIPH patients is determined by presence, recognition and management of associated disorders. With better understanding of the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and may have a pathogenic role. Therapeutic interventions to correct this imbalance may prove to be important in the management of NCIPH. PMID:25755567

  14. Liver and spleen stiffness and other noninvasive methods to assess portal hypertension in cirrhotic patients: a review of the literature.

    PubMed

    Colecchia, Antonio; Marasco, Giovanni; Taddia, Martina; Montrone, Lucia; Eusebi, Leonardo H; Mandolesi, Daniele; Schiumerini, Ramona; Di Biase, Anna R; Festi, Davide

    2015-09-01

    Portal hypertension (PH) is one of the most important causes of morbidity and mortality in patients with chronic liver disease. PH measurement is crucial to stage and predict the clinical outcome of liver cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for assessment of the degree of PH; however, it is an invasive method and has not been used widely. Thus, noninvasive methods have been proposed recently. We critically evaluated serum markers, abdominal ultrasonography, and particularly liver and spleen stiffness measurement, which represent the more promising methods to stage PH degree and to assess the presence/absence of esophageal varices (EV). A literature search was carried out on MEDLINE, EMBASE, Web of Science, and Scopus for articles and abstracts. The search terms used included 'liver cirrhosis', 'portal hypertension', 'liver stiffness', 'spleen stiffness', 'ultrasonography', and 'portal hypertension serum biomarker'. The articles cited were selected on the basis of their relevance to the objective of the review. The results of available studies indicate that individually, these methods have a mild accuracy in predicting the presence of EV, and thus they cannot substitute endoscopy to predict EV. When these tests were used in combination, their accuracy increased. In addition to the PH staging, several serum markers and spleen stiffness measurement can predict the clinical outcome of liver cirrhosis with a good accuracy, comparable to that of hepatic vein pressure gradient. In the future, noninvasive methods could be used to select patients requiring further investigations to identify the best tailored clinical management. PMID:26020376

  15. Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure

    PubMed Central

    Reboredo, Mercedes; Chang, Haisul C. Y.; Barbero, Roberto; Rodríguez-Ortigosa, Carlos M.; Pérez-Vizcaíno, Francisco; Morán, Asunción; García, Mónica; Banales, Jesús M.; Carreño, Norberto; Alegre, Félix; Herrero, Ignacio; Quiroga, Jorge

    2013-01-01

    Objective Only a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamic responders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction with propranolol. Methods Zolmitriptan, propranolol or both were tested in two rat models of portal hypertension: common bile duct ligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters including portal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superior mesenteric artery perfusion pressure and in arterial wall cAMP levels induced by zolmitriptan, propranolol or both. Moreover, we determined the effect of splanchnic sympathectomy on the response of PVP to zolmitriptan. Results In both models of portal hypertension zolmitriptan induced a dose-dependent transient descent of portal pressure accompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomy intensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durable portal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min upon zolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged the elevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranolol prevented the inhibitory effects of β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists. Conclusion Zolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta

  16. Brain Injury After Intracerebral Hemorrhage in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Gang; Bao, Xuhui; Xi, Guohua; Keep, Richard; Thompson, B. Gregory; Hua, Ya

    2011-01-01

    Object Hypertension is the main cause of spontaneous intracerebral hemorrhages (ICH), but the effects of hypertension on ICH-induced brain injury have not been well studied. In this study, we examined ICH-induced brain injury in spontaneously hypertensive rats (SHR). Methods This two-part study was performed on 12 weeks old male SHR and Wistar Kyoto (WKY) rats. First, rats received an intracaudate injection of 0.3 units collagenase and hematoma sizes were determined at 24 hours. Second, rats were injected with 100-μL autologous whole blood into the right basal ganglia. Brain edema, neuronal death, ferritin expression, microglia activation, and neurological deficits were examined. Results Hematoma sizes were the same in SHR and WKY rats 24 hours after collagenase injection. SHR had greater neuronal death and neurological deficits after blood injection. ICH also resulted in higher brain ferritin levels and stronger activation of microglia in SHR. However, perihematomal brain edema was same in the SHR and WKY rats. Conclusion Moderate chronic hypertension resulted in more severe ICH-induced neuronal death and neurological deficits, but did not exaggerate hematoma enlargement and perihematomal brain edema in the rat ICH models. PMID:21294617

  17. Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

    PubMed Central

    Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina

    2011-01-01

    This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors. PMID:21421701

  18. Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

    PubMed Central

    Kim, Moon Young; Jeong, Woo Kyoung; Baik, Soon Koo

    2014-01-01

    With advances in the management and treatment of advanced liver disease, including the use of antiviral therapy, a simple, one stage description for advanced fibrotic liver disease has become inadequate. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension (PHT), respectively, and they have diagnostic and prognostic value. However, they are invasive and, as such, cannot be used repeatedly in clinical practice. The ideal noninvasive test should be safe, easy to perform, inexpensive, reproducible as well as to give numerical and accurate results in real time. It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification. Recently, many types of noninvasive alternative tests have been developed and are under investigation. In particular, imaging and ultrasound based tests, such as transient elastography, have shown promising results. Although most of these noninvasive tests effectively identify severe fibrosis and PHT, the methods available for diagnosing moderate disease status are still insufficient, and further investigation is essential to predict outcomes and individualize therapy in this field. PMID:24764667

  19. Hepatocellular carcinoma in cirrhotic patients with portal hypertension: Is liver resection always contraindicated?

    PubMed Central

    Ruzzenente, Andrea; Valdegamberi, Alessandro; Campagnaro, Tommaso; Conci, Simone; Pachera, Silvia; Iacono, Calogero; Guglielmi, Alfredo

    2011-01-01

    AIM: To analyze the outcome of hepatocellular carcinoma (HCC) resection in cirrhosis patients, related to presence of portal hypertension (PH) and extent of hepatectomy. METHODS: A retrospective analysis of 135 patients with HCC on a background of cirrhosis was submitted to curative liver resection. RESULTS: PH was present in 44 (32.5%) patients. Overall mortality and morbidity were 2.2% and 33.7%, respectively. Median survival time in patients with or without PH was 31.6 and 65.1 mo, respectively (P = 0.047); in the subgroup with Child-Pugh class A cirrhosis, median survival was 65.1 mo and 60.5 mo, respectively (P = 0.257). Survival for patients submitted to limited liver resection was not significantly different in presence or absence of PH. Conversely, median survival for patients after resection of 2 or more segments with or without PH was 64.4 mo and 163.9 mo, respectively (P = 0.035). CONCLUSION: PH is not an absolute contraindication to liver resection in Child-Pugh class A cirrhotic patients, but resection of 2 or more segments should not be recommended in patients with PH. PMID:22171142

  20. [Autoimmune pancreatitis: inflammatory pseudotumor, multifocal fibrosclerosis, portal hypertension, and long-term outcome].

    PubMed

    Beristain, J L; Sabater, L; Calatayud, A; Calvete, J; Rausell, M; Lledó, S; Tosca, J; Sastre, J; Aparisi, L

    2008-10-01

    Autoimmune pancreatitis is a recently characterized disease that still constitutes a diagnostic challenge, especially regarding differential diagnosis from neoplasia. Long-term outcome is poorly known. We herein report a case of a patient with autoimmune pancreatitis and 14 years of follow-up, and show its clinical, biochemical, and morphological characteristics. A 54-year-old female presented with obstructive jaundice and abdominal tenderness, as well as a mass at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery showed an increase of the whole pancreas, malignancy was intraoperatively ruled out, and a cholecystectomy and choledochoduodenostomy were carried out. The diagnosis was chronic pancreatitis. Over the following years different autoimmune complications developed, including asthma, salivary gland swelling, and sclerosing cholangitis, as well as recurrent episodes of jaundice, and exocrine and endocrine pancreatic failure. The development of these complications combined with the demonstration of high serum levels of IgG4 and carbonic anhydrase II led to a re-evaluation of the initial histology of the pancreas, leading to a final diagnosis of autoimmune pancreatitis: IgG4+ lymphoplasmacytic infiltrates, fibrosis, and obliterative phlebitis. New complications developed during the last few years: retroperitoneal fibrosis with portal hypertension, esophageal varices, and splenomegaly. PMID:19119794

  1. Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis-induced portal hypertension

    PubMed Central

    Tokai, Koichi; Miyatani, Hiroyuki; Yoshida, Yukio; Yamada, Shigeki

    2012-01-01

    A 75-year old man had been diagnosed at 42 years of age as having polycythemia vera and had been monitored at another hospital. Progression of anemia had been recognized at about age 70, and the patient was thus referred to our center in 2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy findings. Hematemesis due to rupture of esophageal varices occurred in January and February of 2011. The bleeding was stopped by endoscopic variceal ligation. Furthermore, in March of the same year, hematemesis recurred and the patient was transported to our center. He was in irreversible hemorrhagic shock and died. The autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers, an observation consistent with myelofibrosis. The liver weighed 1856 g the spleen 1572 g, indicating marked hepatosplenomegaly. The liver and spleen both showed extramedullary hemopoiesis. Myelofibrosis is often complicated by portal hypertension and is occasionally associated with gastrointestinal hemorrhage due to esophageal varices. A patient diagnosed as having myelofibrosis needs to be screened for esophageal/gastric varices. Myelofibrosis has a poor prognosis. Therefore, it is necessary to carefully decide the therapeutic strategy in consideration of the patient’s concomitant conditions, treatment invasiveness and quality of life. PMID:22851873

  2. Sodium ferulate lowers portal pressure in rats with secondary biliary cirrhosis through the RhoA/Rho-kinase signaling pathway: A preliminary study

    PubMed Central

    WEI, LAI; YANG, JUAN; WANG, MIN; XU, SHENG-NAN; LIANG, HUA-MIN; ZHOU, QI

    2014-01-01

    Cirrhotic rats show higher expression levels of hepatic RhoA and Rho-kinase than normal healthy rats, and the activation of this signaling pathway leads to portal hypertension. Sodium ferulate (SF) has been shown to decrease the production of geranylgeranyl pyrophosphate (GGPP), a substance essential for RhoA activation. In the present study, to investigate the effects of SF on fibrosis, portal hypertension and the RhoA/Rho-kinase pathway, hepatic cirrhosis was induced in rats by bile duct ligation. Liver function and fibrogenesis-related biochemical parameters, the hepatic hydroxyproline content, the pathological characteristics of the liver sections and the levels of hepatic α-smooth muscle actin (α-SMA; by immunohistochemistry) were analyzed to assess effects of SF on hepatic fibrosis. In addition, hepatic RhoA, Rho-kinase and endothelial nitric oxide synthase (eNOS) expression was examined by immunohistochemistry. Apoptosis in the SF-treated and SF + GGPP-treated rat primary hepatic stellate cells (HSCs) and a human stellate cell line (LX-2) was examined by flow cytometry. Intrahepatic resistance and responsiveness to the α1-adrenoceptor agonist, methoxamine, were investigated by in situ liver perfusion. Treatment with SF did not affect fibrosis-related biochemical parameters or the hydroxyproline content; however, SF reduced the histological evidence of fibrosis and hepatocyte damage. The SF-treated rats had a significantly lower expression of α-SMA and Rho-kinase, as well as an increased hepatic eNOS content; however, SF did not affect RhoA expression. The SF-treated HSCs had a significantly increased apoptotic rate compared to the untreated rats. Following the addition of GGPP, the rate apoptotic rate decreased. SF reduced basal intrahepatic resistance and the responsiveness of hepatic vascular smooth muscle to methoxamine. Therefore, our data demonstrate that SF reduces fibrogenesis, decreases portal pressure in cirrhotic rats and inhibits the

  3. Sex differential of methylmercury toxicity in spontaneously hypertensive rats (SHR)

    SciTech Connect

    Tamashiro, H.; Arakaki, M.; Akagi, H.; Hirayama, K.; Murao, K.; Smolensky, M.H.

    1986-12-01

    During a study of the effect of MeHg on blood pressure in spontaneously hypertensive rats (SHR), extensive differences between males and females in mercury toxicity were observed. The SHR model, which was developed for studying spontaneous hypertension in animals and essential hypertension in man, is used widely today for this purpose. Since the sex differences in MeHg intoxication have never been reported in SHR, it was thought the findings worthy of publication. Herein, the findings on sex differences in morbidity, mortality and blood pressure of SHR treated orally with MMC (2 mg/kg/day) for 26 consecutive days are presented.

  4. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni

    PubMed Central

    Pereira, Thiago A.; Syn, Wing-Kin; Machado, Mariana V.; Vidigal, Paula V.; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M.; Santos, Elisângela T.; Chan, Isaac S.; Trindade, Guilherme V.M.; Choi, Steve S.; Witek, Rafal P.; Pereira, Fausto E.; Secor, William E.; Andrade, Zilton A.; Lambertucci, José Roberto

    2015-01-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. PMID:26201095

  5. Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results

    PubMed Central

    Lee, Edward W; Saab, Sammy; Gomes, Antoinette S; Busuttil, Ronald; McWilliams, Justin; Durazo, Francisco; Han, Steven-Huy; Goldstein, Leonard; Tafti, Bashir A; Moriarty, John; Loh, Christopher T; Kee, Stephen T

    2014-01-01

    OBJECTIVES: To describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage. METHODS: From October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up. RESULTS: A 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days. CONCLUSIONS: CARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding. PMID:25273155

  6. The portal lobule in rat liver fibrosis: a re-evaluation of the liver unit.

    PubMed

    Bhunchet, E; Wake, K

    1998-02-01

    We re-evaluated three schemes of liver organization: the classic lobule, the portal lobule, and Rappaport's liver acinus. The lobular angioarchitecture of normal rat liver and the three-dimensional structure of pseudolubules found in rat livers with fibrosis induced by swine serum were compared with the classic lobule of the pig. Normal and fibrotic rat livers and pig livers were perfused, injected with either India ink or 0.75% OsO4 through the portal and/or hepatic vein, and immersionfixed. Whole lobes and hand-cut thick sections were made transparent with a solution of benzyl benzoate and methyl salicylate. The angioarchitecture of normal rat liver differs from pig liver. In the former, terminal portal branches and central veins interdigitate, and in the latter, numerous terminal portal branches that arise from interlobular portal veins establish a vascular basket surrounding one central vein and forming classic lobule. The structure of liver acinus is never found in the pig liver. The terminal portal branch, together with the terminal hepatic artery and bile duct, are present inside each pseudolobule of fibrotic rat livers. Blood from the terminal portal branch flows through inlet venules into radiating sinusoids, and, at the periphery converges into newly formed septal and angular outlet venules; these venules terminate in fibrotic central veins located at each corner. Pseudolobules are not rugby ball-like as Rappaport's liver acini are but are polyhedron in shape. The rat pseudolobules are comparable with the portal lobule; its structure and microcirculation are the reverse of the pig classic lobule. Rat pseudolobules are different from liver acini, as shown by the following: 1) their three-dimensional shape is different; and 2) they have a reverse relationship to classic lobules while acini are defined to subdivide classic lobules. In normal and fibrotic rat livers, the liver unit is the portal lobule with a terminal portal branch as the axial branch and

  7. Antihypertensive effects of Gynura procumbens extract in spontaneously hypertensive rats.

    PubMed

    Kim, Mi-Ja; Lee, Hee Jae; Wiryowidagdo, Sumali; Kim, Hye Kyung

    2006-01-01

    Aqueous extracts of Gynura procumbens (Lour.) Merr. were orally administered to spontaneously hypertensive (SHR) rats for 4 weeks, and antihypertensive effects were determined. Oral administration of 500 mg/kg of G. procumbens (Lour.) Merr. extract (GPE) resulted in significantly lower blood pressure in SHR rats compared with SHR rats not given GPE (P < .05). Furthermore, GPE-administered rats had significantly lower serum lactate dehydrogenase, creatine phosphate kinase, and increased nitric oxide (NO), a known vasodilator, compared with the non-GPE-administered SHR group (P < .05). These results suggest that oral administration of aqueous GPE may be useful for prevention and treatment of hypertension through increasing NO production in blood vessels. PMID:17201650

  8. Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data

    PubMed Central

    Kim, Hyung Ki; Kim, Yoon Jun; Chung, Woo Jin; Kim, Soon Sun; Shim, Jae Jun; Choi, Moon Seok; Kim, Do Young; Jun, Dae Won; Um, Soon Ho; Park, Sung Jae; Woo, Hyun Young; Jung, Young Kul; Baik, Soon Koo; Kim, Moon Young; Park, Soo Young; Lee, Jae Myeong

    2014-01-01

    Background/Aims This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis. Methods Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals. Results Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality. Conclusions A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients. PMID:24757655

  9. Transjugular Endovascular Recanalization of Splenic Vein in Patients with Regional Portal Hypertension Complicated by Gastrointestinal Bleeding

    SciTech Connect

    Luo, Xuefeng; Nie, Ling; Wang, Zhu; Tsauo, Jiaywei; Tang, Chengwei; Li, Xiao

    2013-05-02

    PurposeRegional portal hypertension (RPH) is an uncommon clinical syndrome resulting from splenic vein stenosis/occlusion, which may cause gastrointestinal (GI) bleeding from the esophagogastric varices. The present study evaluated the safety and efficacy of transjugular endovascular recanalization of splenic vein in patients with GI bleeding secondary to RPH.MethodsFrom December 2008 to May 2011, 11 patients who were diagnosed with RPH complicated by GI bleeding and had undergone transjugular endovascular recanalization of splenic vein were reviewed retrospectively. Contrast-enhanced computed tomography revealed splenic vein stenosis in six cases and splenic vein occlusion in five. Etiology of RPH was chronic pancreatitis (n = 7), acute pancreatitis with pancreatic pseudocyst (n = 2), pancreatic injury (n = 1), and isolated pancreatic tuberculosis (n = 1).ResultsTechnical success was achieved in 8 of 11 patients via the transjugular approach, including six patients with splenic vein stenosis and two patients with splenic vein occlusion. Two patients underwent splenic vein venoplasty only, whereas four patients underwent bare stents deployment and two covered stents. Splenic vein pressure gradient (SPG) was reduced from 21.5 ± 7.3 to 2.9 ± 1.4 mmHg after the procedure (P < 0.01). For the remaining three patients who had technical failures, splenic artery embolization and subsequent splenectomy was performed. During a median follow-up time of 17.5 (range, 3–34) months, no recurrence of GI bleeding was observed.ConclusionsTransjugular endovascular recanalization of splenic vein is a safe and effective therapeutic option in patients with RPH complicated by GI bleeding and is not associated with an increased risk of procedure-related complications.

  10. Portal Hypertension in Children With Wilms' Tumor: A Report From the National Wilms' Tumor Study Group

    SciTech Connect

    Warwick, Anne B.; Kalapurakal, John A.; Ou, San-San; Green, Daniel M.; Norkool, Pat A.; Peterson, Susan M.; Breslow, Norman E.

    2010-05-01

    Purpose: This analysis was undertaken to determine the cumulative risk of and risk factors for portal hypertension (PHTN) in patients with Wilms' tumor (WT). Methods and Materials: Medical records were reviewed to identify cases of PHTN identified with late liver/spleen/gastric toxicities in a cohort of 5,195 patients treated with National Wilms' Tumor Studies (NWTS) protocols 1 to 4. A nested case control study (5 controls/case) was conducted to determine relationships among doxorubicin, radiation therapy (RT) dose to the liver, patient gender, and PHTN. Conditional logistic regression was used to estimate adjusted hazard ratios (HR) of PHTN associated with these factors. Results: Cumulative risk of PHTN at 6 years from WT diagnosis was 0.7% for patients with right-sided tumors vs. 0.1% for those with left-sided tumors (p = 0.002). Seventeen of 19 cases were evaluable for RT. The majority of cases (16/17 [94%]) received right-flank RT either alone or as part of whole-abdomen RT and received >15 Gy to the liver. Fifteen of 17 (88%) patients received a higher dose to the liver than they would have with modern WT protocols. Controlling for RT dose, the HR was 3.0 for patients who received doxorubicin (p = 0.32) and 2.8 for females (p = 0.15). Controlling for doxorubicin, the 95% lower confidence bound on the HR associating PHTN with a minimum liver RT dose of >15 Gy vs. <=15 Gy was 2.5 (p = 0.001); it was 2.4 for a maximum liver dose of >15 Gy vs. <=15 Gy (p = 0.001). Conclusions: There was a strong association between higher doses of liver RT (>15 Gy) and the development of PHTN among WT patients.

  11. The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension.

    PubMed

    Dunk, A A; Moore, J; Symon, A; Dickie, A; Sinclair, T S; Mowat, N A; Brunt, P W

    1988-04-01

    Beta adrenoreceptor blocking drugs have been used for the prevention of haemorrhage from oesophageal varices. However, it is possible that these agents, by virtue of their effects on hepatic blood flow, may impair liver function and precipitate hepatic encephalopathy. We have therefore studied the effect of the beta blocking drug propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Twenty patients were randomly assigned to receive 4 weeks treatment with propranolol or an identical-looking placebo, the former given in a dose sufficient to reduce resting pulse rate by greater than or equal to 25%. Before and after treatment patients were assessed for the severity of liver disease and the presence of encephalopathy. EEG mean cycle frequency and fasting arterial ammonia concentrations were also measured, and in order to detect latent hepatic encephalopathy, each patient underwent a battery of psychometric tests. Patients were blinded as to their treatment, as were those assessing their responses. Neither propranolol nor placebo had any significant effect on the parameters measured. On propranolol median EEG mean cycle frequency fell from 9.08 ct s-1 (range 8.63-11.0 ct s-1) to 8.73 ct s-1 (range 8.27-11.44 ct s-1), and median fasting arterial ammonia concentration fell from 66 mumol litre-1 (range 40-329 mumol litre-1) to 49 mumol litre-1 (range 37-188 mumol litre-1). Psychometric test values, while initially abnormal and suggestive of latent hepatic encephalopathy in the majority of patients, did not change significantly during the study. PMID:2979240

  12. Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis

    PubMed Central

    Li, Tong; Ke, Wenbo; Sun, Ping; Chen, Xiang; Belgaumkar, Ajay; Huang, Yuanjian; Xian, Wenjing; Li, Jinjin; Zheng, Qichang

    2016-01-01

    Objective To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension. Design A systematic review and meta-analysis. Data sources We searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included. Outcome measure We calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events). Results 12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference −8.49, 95% CI −12.36 to −4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group. Conclusions Carvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions. Trial registration number CRD42015020542. PMID:27147389

  13. A case of non-cirrhotic portal hypertension associated with anti-retroviral therapy in a Japanese patient with human immunodeficiency virus infection.

    PubMed

    Yajima, Keishiro; Uehira, Tomoko; Otera, Hiroshi; Koizumi, Yusuke; Watanabe, Dai; Kodama, Yoshinori; Kuzushita, Noriyoshi; Nishida, Yasuharu; Mita, Eiji; Mano, Masayuki; Shirasaka, Takuma

    2014-09-01

    The diagnosis of non-cirrhotic portal hypertension (NCPH), a rare but potentially life-threatening complication in human immunodeficiency virus (HIV)-positive individuals, often occurs only after the emergence of fatal manifestations such as bleeding of esophageal varices. We herein report a female Japanese HIV patient who developed NCPH approximately 4 years after discontinuation of 65 months of didanosine (ddI) administration. The patient presented with severe ascites, bloody bowel discharge, extreme abdominal swelling, and symptoms of portal hypertension but no sign of liver cirrhosis. Examination revealed esophageal varices, oozing-like bleeding from a wide part of the colon, significant atrophy of the right lobe of the liver, and arterio-portal shunting and recanalization from the left medial segment branch of the portal vein to a paraumbilical vein, but no visible obstruction of the main trunk of the portal vein. Treatment for esophageal varices consisted of coagulation therapy with argon plasma after enforcement by endoscopic sclerotherapy and oral administration of β-blockers for elevated portal blood pressure. The patient has not experienced gastrointestinal bleeding in the approximately 5 years since the diagnosis of NCPH. Reviewing this case suggests the importance of suspecting NCPH in HIV patients with liver dysfunction of unknown etiology with a history of ddI and other purine analogs use, as well as the importance of controlling portal hypertension and esophageal varices in the treatment of NCPH. PMID:25034388

  14. Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine.

    PubMed

    Shepherd, P C; Fooks, J; Gray, R; Allan, N C

    1991-10-01

    Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML. PMID:1958475

  15. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    PubMed

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains. PMID:25300030

  16. Left Ventricular Dilation and Pulmonary Vasodilatation after Surgical Shunt for Treatment of Pre-Sinusoidal Portal Hypertension

    PubMed Central

    2016-01-01

    Objective The aim of this study was to prospectively investigate the long-term cardiovascular and pulmonary hemodynamic effects of surgical shunt for treatment of portal hypertension (PH) due to Schistosomiasis mansoni. Location The University of São Paulo Medical School, Brazil; Public Practice. Methods Hemodynamic evaluation was performed with transesophageal Doppler and contrast-enhanced echocardiography (ECHO) on twenty-eight participants with schistosomal portal hypertension. Participants were divided into two groups according to the surgical procedure used to treat their schistosomal portal hypertension within the last two years: group 1—distal splenorenal shunt (DSRS, n = 13) and group 2—esophagogastric devascularization and splenectomy (EGDS, n = 15). Results The cardiac output (5.08 ± 0.91 L/min) and systolic volume (60.1 ± 5.6 ml) were increased (p = 0.001) in the DSRS group. DSRS participants had a significant increase (p < 0.0001) in their left ventricular end-systolic and end-diastolic diameters as well as in their left ventricular end-diastolic and end-systolic volumes (p < 0.001) compared with the preoperative period. No statistically significant difference was found in the patients who underwent EGDS. ECHO revealed intrapulmonary vasodilatation (IPV) in 18 participants (64%), 9 DSRS and 9 EGDS (p > 0.05). Conclusions The late increase in the cardiac output, stroke volume and left ventricular diameters demonstrated left ventricular dilatation after a distal splenorenal shunt. ECHO revealed a greater prevalence for IPV in patients with schistosomiasis than has previously been described in patients with PH from liver cirrhosis. PMID:27119143

  17. TIPS treatment in a patient with severe lower gastrointestinal bleeding with a misdiagnosis of cirrhotic portal hypertension.

    PubMed

    Laborda, Alicia; Guirola, José Andrés; Medrano, Joaquín; Simón, Miguel Ángel; Ioakeim, Ignatios; de-Gregorio, Miguel Ángel

    2015-12-01

    Abernethy malformation is a rare abnormal embryological development of splanchnic venous system characterised by the presence of a congenital extrahepatic portosystemic shunt. We present a rare case of an adult male patient that was admitted with severe lower gastrointestinal bleeding, requiring multiple blood transfusions. The patient's medical history and the laboratory tests performed led to the misdiagnosis of a congenital Abernethy malformation. We present a rare case, discussing the reasons for the misdiagnosis and we conclude that management of clinical data and imaging are highly important to discard these types of congenital malformations that can mimic a portal hypertension condition. PMID:26671592

  18. Development of nodular regenerative hyperplasia (NRH) with portal hypertension following the administration of oxaliplatin for the recurrence of colon cancer.

    PubMed

    Takaya, Hiroaki; Kawaratani, Hideto; Nakanishi, Keisuke; Takeyama, Shinya; Morioka, Chie; Sawai, Masayoshi; Toyohara, Masahisa; Fujimoto, Masao; Yoshiji, Hitoshi; Yamao, Junichi; Fukui, Hiroshi

    2015-01-01

    Nodular regenerative hyperplasia (NRH) is associated with autoimmune and hematologic diseases and may lead to portal hypertension. We herein report a case of NRH diagnosed based on a liver biopsy. A 63-year-old woman developed esophageal varices and splenomegaly. She had undergone surgery for transverse colon cancer 24 years earlier and received systemic chemotherapy (FOLFOX4 including oxaliplatin) to treat lymph node metastasis 21 years after the operation. The present liver biopsy confirmed NRH, and, after two years, she received endoscopic injection sclerotherapy. Oxaliplatin was suspected to be the causative agent of NRH in this case. Therefore, physicians must consider the possibility of NRH in patients who receive chemotherapy. PMID:25748953

  19. Aqueous extract of dioscorea opposita thunb. normalizes the hypertension in 2K1C hypertensive rats

    PubMed Central

    2014-01-01

    Background Dioscorea opposita Thunb. (Huai Shan Yao, DOT), a common staple food in China, has been used for more than 2000 years in traditional Chinese medicine (TCM) to treat different systemic diseases including hypertension. The objective of this study was to investigate the possible antihypertensive effects of the aqueous extract of (DOT) in renovascular hypertensive rats as well as the mechanism in reducing blood pressure. Methods The two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in Wistar rats. Rats with captopril, low-dose DOT and high-dose DOT treated 2K1C groups for 6 weeks. The blood pressure, cardiac mass index (heart weight/body weight), plasma level of angiotensin-II (Ang-II), endothelin-1(ET-1), superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated. Results DOT significantly reduced mean systolic and diastolic blood pressure after treatment. DOT also significantly increased plasma SOD activity but decreased plasma MDA concentration. Renal function was improved with captopril and DOT. DOT reduced plasma Ang-II activity and plasma ET concentration. They couldalso significantly reduce the left ventricular hypertrophy and cardiac mass index. Conclusions Our results suggest that DOT may have an antihypertensive effect on hypertension by inhibit ET-converting enzyme and antioxidant activity, which warrant further exploration. PMID:24447776

  20. Role of Musclin in the Pathogenesis of Hypertension in Rat

    PubMed Central

    Li, Ying-Xiao; Cheng, Kai-Chun; Asakawa, Akihiro; Kato, Ikuo; Sato, Yuki; Amitani, Haruka; Kawamura, Namiko; Cheng, Juei-Tang; Inui, Akio

    2013-01-01

    Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. Musclin possesses a region homologous to the natriuretic peptide family. Thus, musclin is found to bind with the natriuretic peptide clearance receptors. However, the role of musclin in vascular regulation remains unclear. In this study, we aim to investigate the direct effect of musclin on vascular tone and to analyze its role in hypertension using the spontaneously hypertensive rats (SHR). In aortic strips isolated from SHR, musclin induced contractions in a dose-dependent manner. We found that the musclin-induced vasoconstriction was more marked in SHR than in normal rats (WKY). Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody. Therefore, mediation of the natriuretic peptide receptor in musclin-induced vasoconstriction can be considered. In addition, similar to the natriuretic peptide receptor, expression of the musclin gene in blood vessels was higher in SHR than in WKY. Injection of musclin markedly increased the blood pressure in rats that can be inhibited by anti-musclin antibodies. Musclin-induced vasoconstriction was more pronounced in SHR than in WKY as in its expression. Taken together, these results suggest that musclin is involved in blood pressure regulation. The higher expression of musclin in hypertension indicates that musclin could be used as a new target for the treatment of hypertension in the future. PMID:23940802

  1. The spectrum of gastric pathology in portal hypertension-An endoscopic and pathologic study of 550 cases.

    PubMed

    Ma, Changqing; Chen, Chien-Huan; Liu, Ta-Chiang

    2016-08-01

    One of the main tasks for pathologists when evaluating gastric biopsies from patients with portal hypertensive gastropathy (PHG) is to examine whether there is increased mucosal vasculature as suggested by endoscopy. However, the full spectrum of pathology findings in patients with portal hypertension (pHTN) is largely unknown. We systematically characterized the endoscopic and pathologic features in gastric biopsies from pHTN patients (study group) and compared with those from patients without pHTN (control group). The study group consisted of 550 consecutive surveillance esophagogastroduodenoscopic (EGD) biopsies, whereas the control group included 281 consecutive EGD biopsies for a variety of indications. As expected, the endoscopic prevalence of PHG was 28%, among which two-thirds showed corresponding histopathologic evidence of increased vasculature. However, non-Helicobacter pylori gastritis was the most common finding in pHTN patients on histology (40%). In addition, hyperplastic polyp was also more common in pHTN patients than in controls (6% vs 3%; P=0.0314). In contrast, pathology findings of nonspecific reactive changes (29% vs 51%; P<0.0001), proton pump inhibitor-related changes (16% vs 30%; P<0.0001), and malignancy (1% vs 3%; P=0.0138) were less common in pHTN patients. Our results show a spectrum of gastric endoscopic and pathologic findings in pHTN patients. The predominant gastric pathology in pHTN patients may be associated with pHTN-induced gastric microcirculation impairment. PMID:27461830

  2. Activation of portal-hepatic osmoreceptors in rats: role of calcium, acetylcholine and cyclic AMP.

    PubMed

    Stoppini, L; Baertschi, A J

    1984-11-01

    Osmoreceptors are sensory organs of paramount importance in water and electrolyte balance, yet the mechanisms for their activation are virtually unknown. Peripheral osmoreceptors have been localised in the hepatic portal vein area of rats. We thus superfused the portal adventitia with 0.2 ml of 4% NaCl before and after various pharmacological pretreatments (0.4 ml of 1 mM solutions) of the portal area, while monitoring the neural activity of the hypothalamo-neurohypophysial system. Portal superfusion with verapamil, to reduce Ca-influx, reversibly inhibited the response to osmotic stimuli by up to 50% (P less than 0.0005). Such inhibition (58%; P less than 0.0005) was also seen with portal superfusion by atropine. Atropine did not affect hypothalamo-neurohypophysial responses to stimulation of portal bradykinin receptors with 0.2 ml 1 muM bradykinin, and portal superfusion with acetylcholine activated the hypothalamo-neurohypophysial system. The results thus support the hypothesis of a cholinergic neurotransmission linking portal osmoreceptive structures and afferent nerve endings. Diamide, which inhibits water efflux in frog skin, also reversibly inhibited responses to osmotic stimuli by 38% (P less than 0.0005). Pretreatments with trifluoperazine, a calmodulin inhibitor, and cordycepin, an adenylate cyclase inhibitor, diminished responses to osmotic stimuli by 30-45% (P less than 0.005), while cAMP and theophilline potentiated them by 38% (P less than 0.0005). Responses to bradykinin superfusion were reduced 20-30% (P less than 0.05) by both cordycepin and cAMP. The results suggest that portal osmoreceptors release acetylcholine to excite afferent nerves when exposed to an osmotic gradient. The mechanism of this release may be mediated by an efflux of water and an increase of intracellular calcium activity and cAMP. PMID:6150955

  3. Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

    PubMed Central

    Plante, G E; Bissonnette, M; Sirois, M G; Regoli, D; Sirois, P

    1992-01-01

    Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR. PMID:1602008

  4. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats.

    PubMed

    Li, Yali; Liu, Jian; Gao, Dengfeng; Wei, Jin; Yuan, Haifeng; Niu, Xiaolin; Zhang, Qiaojun

    2016-03-01

    The aim of the present study was to investigate the age‑related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase‑3). In addition, the expression of PPAR‑γ and Bcl‑2 were progressively reduced with increasing age in the SHR group. The 32 and 64‑week‑old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro‑apoptotic proteins compared with age‑matched WKY rats, which was accompanied by reduced expression of PPAR‑γ. Compared with the 16 and 32‑week‑old WKY group, the 64‑week‑old WKY rats exhibited increased oxidative stress and pro‑apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR‑γ may contribute to the age‑related brain damage in SHRs. PMID:26846626

  5. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  6. The Accuracy of Ultrasonography for the Evaluation of Portal Hypertension in Patients with Cirrhosis: A Systematic Review

    PubMed Central

    Kim, Gaeun; Cho, Youn Zoo; Kim, Moon Young; Hong, Won Ki; Kwon, Sang Ok

    2015-01-01

    Objective Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis. Materials and Methods We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies. Results A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69-88% and 67-75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296-0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9-77.8% and 81.8-100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545-0.649). Conclusion Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH. PMID:25741193

  7. Psychobiology of experimental hypertension: evaluation of the Dahl rat lines

    SciTech Connect

    Haber, S.B.; Friedman, R.

    1981-01-01

    The Dahl salt-sensitive (DS) and salt-resistant (DR) rat lines were selectively bred to show opposite genetically determined blood pressure responses to excess sodium chloride ingestion. These animals have provided significant anatomical, physiological, and biochemical data concerning the pathological mechanisms of experimental hypertension. Research is also being conducted to determine the relevance of psychobiological and behavioral variables in these two lines. The rationale for the selection and maintenance of the Dahl model and the physiological, biochemical, and behavioral characteristics which distinguish DS and DR rats are presented. Although originally developed for the study of salt-induced hypertension, special attention is given to the application of this animal model in behavior genetic research, stressing its inherent advantages and limitations. The use of the Dahl model in psychobiological studies and the utility of the model for future behavioral, genetic, and psychophysiological research are also detailed.

  8. Candidate genes for hypertension: insights from the Dahl S rat.

    PubMed

    Rudemiller, Nathan P; Mattson, David L

    2015-12-15

    Human genetic linkage and association studies have nominated many genes as possible contributors to disease. Mutating or deleting these genes in a relevant disease model can validate their association with disease and potentially uncover novel mechanisms of pathogenesis. Targeted genetic mutagenesis has only recently been developed in the rat, and this technique has been applied in the Dahl salt-sensitive (S) rat to investigate human candidate genes associated with hypertension. This mini-review communicates the findings of these studies and displays how targeted genetic mutagenesis may contribute to the discovery of novel therapies for patients. PMID:25877508

  9. The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats

    PubMed Central

    Moreno, Enrique; Moral-Sanz, Javier; Barreira, Bianca; Galindo, Pilar; Pandolfi, Rachele; Jimenez, Rosario; Moreno, Laura; Cogolludo, Angel; Duarte, Juan; Perez-Vizcaino, Francisco

    2014-01-01

    Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH. PMID:25460361

  10. Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.

    PubMed

    Shirakura, Takashi; Nomura, Johji; Matsui, Chieko; Kobayashi, Tsunefumi; Tamura, Mizuho; Masuzaki, Hiroaki

    2016-08-01

    Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 ± 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 ± 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics. PMID:27198514

  11. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  12. Reversal of Endothelial Dysfunction by GPBAR1 Agonism in Portal Hypertension Involves a AKT/FOXOA1 Dependent Regulation of H2S Generation and Endothelin-1

    PubMed Central

    Renga, Barbara; Cipriani, Sabrina; Carino, Adriana; Simonetti, Michele; Zampella, Angela; Fiorucci, Stefano

    2015-01-01

    Background GPBAR1 is a bile acids activated receptor expressed in entero-hepatic tissues. In the liver expression of GPBAR1 is restricted to sinusoidal and Kuppfer cells. In the systemic circulation vasodilation caused by GPBAR1 agonists is abrogated by inhibition of cystathione-γ-liase (CSE), an enzyme essential to the generation of hydrogen sulfide (H2S), a vasodilatory agent. Portal BAR501 is a semisynthetic bile acid derivative endowed with a potent and selective agonistic activity toward GPBAR1. Methods Cirrhosis was induced in mice by carbon tetrachloride (CCL4) administration for 9 weeks. Liver endothelial dysfunction was induced by feeding wild type and Gpbar1-/- mice with methionine for 4 weeks. In both models, mice were administered BAR501, 15 mg/kg/day. Results By transactivation assay we demonstrate that BAR501 is a selective GPBAR1 agonist devoid of any FXR agonistic activity. In naïve rats, BAR501 effectively reduced hepatic perfusion pressure and counteracted the vasoconstriction activity of norepinephrine. In the CCl4 model, 9 weeks treatment with BAR501 effectively protected against development of endothelial dysfunction by increasing liver CSE expression and activity and by reducing endothelin (ET)-1 gene expression. In mice feed methionine, treatment with BAR501 attenuated endothelial dysfunction and caused a GPBAR1-dependent regulation of CSE. Using human liver sinusoidal cells, we found that modulation of CSE expression/activity is mediated by both genomic (recruitment of CREB to CRE in the CSE promoter) and non-genomic effects, involving a Akt-dependent phosporylation of CSE and endothelial nitric oxide (NO) synthase (eNOS). BAR501, phosphorylates FOXO1 and inhibits ET-1 transcription in liver sinusoidal cells. Conclusions BAR501, a UDCA-like GPBAR1 agonist, rescues from endothelial dysfunction in rodent models of portal hypertension by exerting genomic and non-genomic effects on CSE, eNOS and ET-1 in liver sinusoidal cells. PMID:26539823

  13. Sympathetic activation in rats with L-NAME-induced hypertension.

    PubMed

    Biancardi, V C; Bergamaschi, C T; Lopes, O U; Campos, R R

    2007-03-01

    We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension. PMID:17334538

  14. Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats.

    PubMed

    Zhu, Jun; Zhang, Yantao; Yang, Changhai

    2015-02-01

    Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms. PMID:25352064

  15. Potassium channels and vascular reactivity in genetically hypertensive rats.

    PubMed

    Furspan, P B; Webb, R C

    1990-06-01

    In hypertension, membrane potassium permeability and vascular reactivity are increased. This study characterizes a potassium-selective channel and contractions to barium, a potassium channel inhibitor, in vascular smooth muscle (tail artery) from spontaneously hypertensive stroke-prone rats (SHRSP) and normotensive Wistar-Kyoto (WKY) rats. Smooth muscle cells were isolated by enzymatic digestion, and potassium channel activity was characterized by using patch-clamp technique (inside-out configuration). Isometric contractile activity was evaluated in helically cut arterial strips by using standard muscle bath methodology. In membrane patches, a voltage-gated, calcium-insensitive, potassium-selective channel of large conductance (200 picosiemens) was observed. The channel did not conduct sodium or rubidium. Barium (10(-6) to 10(-4) M) produced a dose-dependent blockade of channel activity. These channel characteristics did not differ in SHRSP and WKY rat cells. After treatment with 35 mM KCl, barium (10(-5) to 10(-3) M) caused greater contractions in SHRSP arteries compared with arteries in WKY rats. The contractions to barium were markedly attenuated in calcium-free solution, and nifedipine and verapamil abolished contractions induced by barium in depolarizing solution. We conclude that increased vascular reactivity to barium in SHRSP arteries is not due to an alteration in the biophysical properties of the potassium channel studied. PMID:2351424

  16. Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).

    PubMed

    Furedi, Nora; Miko, Alexandra; Aubrecht, Bianka; Gaszner, Balazs; Feller, Diana; Rostas, Ildiko; Tenk, Judit; Soos, Szilvia; Balasko, Marta; Balogh, Andras; Pap, Marianna; Petervari, Erika

    2016-08-01

    Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR. PMID:27339773

  17. Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

    NASA Technical Reports Server (NTRS)

    Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

    1990-01-01

    Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

  18. Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats

    PubMed Central

    Lee, Tzu-Cheng; Burghardt, Andrew J.; Yao, Wei; Lane, Nancy E.; Majumdar, Sharmila; Gullberg, Grant T.; Seo, Youngho

    2014-01-01

    A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher BMD than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography (μCT) to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20-month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension. PMID:25106873

  19. Blood pressure reduction by CCl/sub 4/ in the spontaneously hypertensive rat

    SciTech Connect

    Loyke, H.F.

    1988-07-01

    It has been established that the spontaneously hypertensive rat (SHR) presents an experimental model whose pathogenesis resembles that of essential hypertension in man. A great advantage of this model is that the entire life history of this disease is compressed within a time frame of two years. Many antihypertensive agents have been found effective in reducing blood pressure in SHR animals. Carbon tetrachloride (CCl/sub 4/) treatment has resulted in blood pressure reduction and subsequent elevation after discontinuing treatment in Grollman renal hypertensive rats and in endocrine hypertensive rats. The purpose of this study was to determine whether hypertension in the spontaneously hypertensive rat (SHR), could be modified by CCl/sub 4/ treatment and to evaluate its effects on kidney and liver tissue.

  20. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    SciTech Connect

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  1. Severe pulmonary arterial hypertensive rats are tolerant to mild exercise

    PubMed Central

    Hartman, Lauren J.; Scruggs, April K.; McLendon, Jared M.; Haven, April K.; Bauer, Natalie N.

    2015-01-01

    Abstract A frequently used end point of clinical outcomes in patients with pulmonary arterial hypertension (PAH) is the 6-minute walk distance. Furthermore, some data suggest that mild to moderate exercise as an intervention in stable PAH is beneficial. Some of these questions have been recapitulated in the monocrotaline and hypoxia animal models of pulmonary hypertension. However, mild exercise and walk distance as end points have not been rigorously examined in the severe progressive Sugen 5416/hypoxia/normoxia (Su/Hx/Nx) animal model of PAH at each stage of worsening disease. Our hypothesis was that animals that were preselected as runners would have increased walk times and improved right ventricle/left ventricle plus septum (RV/LV+S) ratios, echocardiography, and histology compared with nonexercised Su/Hx/Nx animals. We examined four groups of rats: Su/Hx/Nx sedentary, Su/Hx/Nx exercised, control sedentary, and control exercised. Echocardiography was performed at 5, 8, and 13 weeks to assess right ventricular inner diameter in diastole and left ventricular eccentricity index. We found no difference between exercised and sedentary Su/Hx/Nx rats, and both were worsened compared with controls. Rats were euthanized at 13 weeks, and we found that neither RV/LV+S nor the occurrence of occlusive lesions were influenced by exercise. Most interesting, however, was that despite progressive PAH development, exercised Su/Hx/Nx rats showed no decrease in time or distance for treadmill exercise. In all, our data suggest that, despite severe PAH development, Su/Hx/Nx rats retain the same treadmill exercise capacity as control animals. PMID:26064461

  2. Cinnamaldehyde Attenuates Cataractogenesis via Restoration of Hypertension and Oxidative Stress in Fructose-Fed Hypertensive rats

    PubMed Central

    Singh, Amrita; Khan, Samsroz Ahmad; Choudhary, Rajesh

    2016-01-01

    Objectives: Several studies have revealed that systemic hypertension is strongly associated with cataractogenesis. However, the pathophysiology and treatment is often unclear. In this study, we evaluated the anti-cataractogenic effect of cinnamaldehyde (CA), a natural organic compound, in rats with fructose-induced hypertension. Methods: The rats were divided into six groups. For six weeks, the normal group received a suspension of 0.5% carboxy methyl cellulose (10 mL/kg/day, p.o.) while five other groups received a 10% (w/v) fructose solution in their drinking water to induce hypertension. By the end of the third week hypertension had been induced in all the animals receiving fructose. From the beginning of the fourth week to the end of the sixth week, one of those five groups (control) continued to receive only 10% (w/v) fructose solution, one group (standard) received ramipril (1 mg/kg/day, p.o.) plus 10% (w/v) fructose solution, and three groups (experimental) received CA at doses of 20, 30, and 40 mg/kg/day p.o., plus 10% (w/v) fructose solution. Blood pressure was measured weekly using a non-invasive blood pressure apparatus. After six weeks, the animals were sacrificed, and the anti-cataractogenic effects on the eye lenses were evaluated. Results: Administration of fructose elevated both the systolic and the diastolic blood pressures, which were significantly reduced by CA at all dose levels. In the control group, a significant increase in the malonaldehyde (MDA) level and decreases in the total protein, Ca2+adenosine triphosphate (ATP)ase activity, glutathione peroxidase, catalase, superoxide dismutase and glutathione levels, as compared to the normal group, were observed. Administration of CA at all doses significantly restored the enzymatic, non-enzymatic, antioxidants, total protein, and Ca2+ATPase levels, but decreased the MDA level, as compared to the control group. Conclusion: The present study revealed that CA modulated the antioxidant parameters of

  3. Proteomic response to acupuncture treatment in spontaneously hypertensive rats.

    PubMed

    Lai, Xinsheng; Wang, Jiayou; Nabar, Neel R; Pan, Sanqiang; Tang, Chunzhi; Huang, Yong; Hao, Mufeng; Yang, Zhonghua; Ma, Chunmei; Zhang, Jin; Chew, Helen; He, Zhenquan; Yang, Junjun; Su, Baogui; Zhang, Jian; Liang, Jun; Sneed, Kevin B; Zhou, Shu-Feng

    2012-01-01

    Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7(th) day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat's systolic pressure was reduced significantly (P<0.01), though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571 ± 15 proteins in normal SD rats' medulla, 576 ± 31 proteins in SHR's medulla, 597 ± 44 proteins in medulla of SHR after acupuncturing Taichong, and 616 ± 18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture. Further

  4. Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

    PubMed

    Bachhav, Sagar S; Patil, Savita D; Bhutada, Mukesh S; Surana, Sanjay J

    2011-10-01

    The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 μg/kg/day s.c.) or saline (vehicle) for 10 days. In a prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days, followed by dexamethasone or saline for 10 days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any significant effect on the dexamethasone-induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.) prevents dexamethasone-induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action. PMID:21953707

  5. Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

    PubMed Central

    Bosch, Jaume; Groszmann, Roberto J.; Shah, Vijay H.

    2015-01-01

    Summary Among the common complication of cirrhosis portal hypertension witnessed a major improvement of prognosis during the past decades. Principally due to the introduction of rational treatments based on new pathophysiological paradigms (concepts of thought) developed in the 1980s. The best example being the use of non-selective beta-blockers and of vasopressin analogs, somatostatin, and its analogs. Further refinement in the knowledge of the molecular mechanisms involved in the regulation of both the splanchnic and hepatic circulation has led to the emergence of new treatments, which are based on evidence that show not only structural but also vasoactive components increase the hepatic vascular resistance, as well as of angiogenesis. This knowledge and future improvements will most likely result in more effective treatment of portal hypertension and effective prevention of its complications in early stages. PMID:25920081

  6. HYPOGENESIS OF RIGHT LOBE OF LIVER ACCOMPANIED BY PORTAL HYPERTENSION AND ESOPHAGOGASTRIC VARICEAL BLEEDING; A RARE ANOMALY: A CASE REPORT.

    PubMed

    Gurgenidze, M; Lomidze, N; Chelidze, K; Nemsadze, G; Manijashvili, Z

    2016-04-01

    Hypo-agenesis of the right lobe of the liver is an extremely rare finding. It is defined as the complete or partial absence of liver tissue on the right side without previous disease or surgery. It is usually an incidental finding. A 32-year-old female patient came to Emergency Department of TSMU the First University Clinic 22.10.2015 with an initial diagnosis of upper gastrointestinal bleeding. Her medical history showed no previous diseases of the liver or episodes of hemorrhage. Dizziness, nausea, vomiting with red blood, melena was presented on admission. Esophagogastroduodenoscopy revealed III degree varicose of veins from middle part of the esophagus to cardiofundal part of the stomach. Hemorrhage was observed from cardial part of the stomach. Control of bleeding was not achieved endoscopically. Sengstaken-Blakemore tube was used to stop bleeding temporarily. Computed tomography with angiography was performed. Right lobe of the liver was presented with VII and VIII segments. Medial edge of the left lobe of the liver is located near the spleen. Liver parenchyma is homogenous. No thrombosis of the portal or hepatic veins was revealed. Gallbladder was dislocated laterally and cranially without pathological changes. Extra- and intrahepatic biliary ducts were not dilated. There was colonic interposition between the liver and diaphragm. Diagnosis was established - hypogenesis of right lobe of liver, atrophy-hypertrophy complex, portal hypertension, varicose of the veins of the esophagus and cardiofundal part of the stomach, hemorrhage from variceal vein of the cardial part of the stomach, acquired coagulation factors deficiency, functional hypersplenism, posthemorrhagic anemia. In our case there was congenital hypogenesis of the right lobe of the liver. Five months follow-up showed no recurrent bleeding. PMID:27249427

  7. Anti-hypertensive property of a nickel-piperazine/NO donor in spontaneously hypertensive rats.

    PubMed

    Monti, Martina; Ciccone, Valerio; Pacini, Aurora; Roggeri, Riccardo; Monzani, Enrico; Casella, Luigi; Morbidelli, Lucia

    2016-05-01

    The nickel-piperazine/NO donor compound, Ni(PipNONO)Cl, belonging to the family of compounds labelled as "metal-nonoates", due to its promising vasodilating activity, has been considered as a potential drug candidate in anti-hypertensive therapy. Drug efficacy has been evaluated in spontaneously hypertensive rats (SHR) in comparison with normotensive animals (C57BL/6 mice and WKY rats). In normotensive animals the metal-nonoate maintained blood pressure at basal level both following acute administration and after 30 days of treatment. In SHR, Ni(PipNONO)Cl reduced blood pressure in the dose range of 3-10mg/kg. When compared with a commercial NONOate, DETA/NO, used at the same doses, Ni(PipNONO)Cl was more active in reducing blood pressure in SHR than DETA/NO in the first two weeks, while the effect of the two molecules was similar in the third and fourth week. The degradation and control compound Ni(Pip)Cl2 had no effect on blood pressure and heart rate in same animal models. Remarkably, the blood pressure reduction induced by the new NO-donor Ni(PipNONO)Cl does not evoke changes in the heart rate and tolerance. Considering the mechanisms of vascular protection, 30 days of administration of Ni(PipNONO)Cl improved endothelial function in SHR by upregulating endothelial NO synthase (eNOS) through increased eNOS protein levels and downregulated Caveolin-1 (Cav-1), and by increasing superoxide dismutase 1 (SOD1) protein level in aortae. In cultured endothelial cells Ni(PipNONO)Cl restored the cell functions (cytoskeletal protein expression, migration and proliferation) altered by the inflammatory mediator interleukin-1β (IL-1β), impairing the endothelial to mesenchimal transition. In conclusion, Ni(PipNONO)Cl maintained unaltered blood pressure in normotensive mice and rats, and it exerted anti-hypertensive effect in SHR through the restoration of vascular endothelial protective functions. PMID:27063892

  8. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

    PubMed Central

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  9. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats.

    PubMed

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  10. Urantide alleviates monocrotaline induced pulmonary arterial hypertension in Wistar rats.

    PubMed

    Mei, Yifang; Jin, Hong; Tian, Wei; Wang, Hao; Wang, Han; Zhao, Yanping; Zhang, Zhiyi; Meng, Fanchao

    2011-08-01

    Pulmonary arterial hypertension (PAH) is a serious disorder with poor prognosis. Urotensin II (UII) has been confirmed to be powerful vasoconstrictor than endothelin-1, which may play an important role in PAH development. The aim of this study is to observe the effects of urantide, a UII receptor antagonist, on monocrotaline (MCT) induced PAH in rats. 60 male Wistar rats were divided into six groups. For early treatment experiment, rats were divided into normal control group, MCT(4w) model group (MCT + saline × 3 wks from the 8th day of MCT injection) and urantide early treatment group (MCT + urantide 10 μg/kg/d × 3 wks, 1 week after MCT injection once). For late treatment experiment, rats were divided as controls, MCT(6w) model group (MCT + saline × 2 wks, 4 weeks after MCT injection once) and urantide late treatment group (MCT + urantide 10 μg/kg/d × 2 wks, 4 weeks after MCT injection once). At the end of experiments, mean pulmonary arterial pressures (mPAP) and mean blood pressure (MBP) of rats in each group were measured by catheterization. Right ventricular weight ratio was also weighed. Relaxation effects of urantide on intralobar pulmonary arterial rings of normal control and MCT(4w) model rats were investigated. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining and immunohistochemistry analysis. Serum nitric oxide (NO) levels in all six groups were assayed by ELISA kits. Urantide markedly reduced the mPAP levels of MCT induced PAH in both early and late treatment groups. It didn't change the MBP. Urantide dose-dependently relaxed the pulmonary arterial rings of normal control and MCT(4w) model rats. Moreover, N(G)-Nitro-l-arginine Methyl Ester (l-NAME) blocked the dilation response induced by urantide. In addition, urantide inhibited the pulmonary vascular remodeling remarkably. Serum NO level elevated in both early and late treatment rats with urantide infusion. These results suggest that urantide effectively alleviated

  11. Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats.

    PubMed Central

    Freslon, J. L.; Giudicelli, J. F.

    1983-01-01

    When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg-1, daily) and captopril (100 mg kg-1, daily) prevent with the same efficacy genetic hypertension development (GHD). Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (-27%), and induced slight reductions in contractility (-12%) and in wall to lumen (W/L) ratio (-15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure. Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (-15%) and their W/L ratio (-30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena. These experiments show that captopril but not dihydralazine has a long-lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD. PMID:6357337

  12. Dietary calcium and magnesium in the development of hypertension in the spontaneously hypertensive rat

    SciTech Connect

    Evans, G.; Weaver, C.M.; Harrington, D.D.; Babbs, C.F.

    1986-03-01

    The role of dietary calcium and magnesium in attenuation of hypertension was studied in 9 groups of 9 spontaneously hypertensive rats ages 8 to 31 weeks. The animals were fed AIN 76 semipurified diets altered in calcium (0.075%, 0.5%, and 2.5%) and magnesium (0.01%, 0.05%, and 0.75%) using a 3 x 3 factorial design. An inverse relationship between dietary calcium and systolic blood pressure as determined by the photoelectric tail cuff method became significant (p<0.05) after 12 weeks. Repeated measures analysis of variance indicated that dietary magnesium had no effect on systolic blood pressure; no calcium x magnesium interaction was observed. Total and ultrafiltrable serum calcium had a significant inverse correlation with blood pressure (-0.4642, p = .001 and -0.5568, p = .001 respectively). Total and ultrafiltrable serum magnesium reflected dietary magnesium concentration. Magnesium deficiency signs, deposition of calcium in kidneys, and histological lesions were observed in high calcium fed groups receiving normal and low levels of magnesium. Thus, a lowering of blood pressure by calcium supplementation without concomitant magnesium supplementation was accompanied by biochemical and histologic abnormalities in this animal model.

  13. Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats

    PubMed Central

    Ribeiro, Rachel Melo; Pinheiro Neto, Vicente Férrer; Ribeiro, Kllysmann Santos; Vieira, Denilson Amorim; Abreu, Iracelle Carvalho; Silva, Selma do Nascimento; Cartágenes, Maria do Socorro de Sousa; Freire, Sônia Maria de Farias; Borges, Antonio Carlos Romão; Borges, Marilene Oliveira da Rocha

    2014-01-01

    This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (Emax⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx. PMID:25614751

  14. In vitro proliferation of aortic smooth muscle cells from spontaneously hypertensive and normotensive rats.

    PubMed

    Pang, S C

    1989-06-01

    The characteristics and proliferation of aortic smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied in culture. Smooth muscle cells were isolated from the tunica media of the thoracic aorta by an explant method. Immunofluorescence microscopy showed that 93-95 per cent of cells were positively labelled with antibodies raised against smooth muscle actin, indicating that these were smooth muscle cells. The proliferative activity was compared between aortic smooth muscle cells from hypertensive and normotensive rats in culture by thymidine incorporation and cell number determinations. The results demonstrate that aortic smooth muscle cells from hypertensive rats grew faster than those from normotensive rats in culture. The increased proliferative activity of cultured aortic smooth muscle cells from hypertensive rats was detectable even when they were cultured in a chemically defined serum-free medium. These data have shown that an increased proliferative activity of aortic smooth muscle cells from hypertensive rats can occur in culture conditions without the influence of arterial pressure or other stimuli as in intact animals. The mechanisms underlying the accelerated proliferative activity of aortic smooth muscle cells from genetically hypertensive rats in vitro remain to be determined. PMID:2754547

  15. Histological evidence of increased turnover in bone from spontaneously hypertensive rats.

    PubMed

    Barbagallo, M; Quaini, F; Baroni, M C; Barbagallo, C M; Boiardi, L; Passeri, G; Arlunno, B; Delsignore, R; Passeri, M

    1991-03-01

    24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls. PMID:1888878

  16. Non-Invasive Diagnosis of Portal Hypertensive Gastropathy: Quantitative Analysis of Microbubble-Induced Stomach Wall Enhancement.

    PubMed

    Kiyono, Soichiro; Maruyama, Hitoshi; Kobayashi, Kazufumi; Kondo, Takayuki; Sekimoto, Tadashi; Shimada, Taro; Yokosuka, Osamu; Yamaguchi, Tadashi

    2016-08-01

    The aim of the study described here was to elucidate the efficacy of contrast-enhanced ultrasound (CEUS) prospectively as a tool in the diagnosis of portal hypertensive gastropathy (PHG). The peak enhancement time at the upper stomach wall (PT) and intensity ratio at the upper stomach/the spleen (IR) between pre- and peak enhancement were evaluated by CEUS with perflubutane microbubble agent in 56 patients, 42 with cirrhosis (16 with PHG) and 14 controls. The IR was higher in patients with PHG (1.21 ± 0.11) than in those without (0.91 ± 0.15, p < 0.05) and the controls (0.78 ± 0.11, p < 0.01), although PT did not differ between these groups. The area under the receiver operating characteristic curve for IR was 0.8199 in the presence of PHG, with the best cutoff value of 0.94, sensitivity 65.9%, specificity 72.6%, positive predictive value 62.2%, negative predictive value 73.1% and accuracy 70.4%. CEUS may have potential as a less invasive tool for diagnosis of PHG in patients with cirrhosis. PMID:27166020

  17. Diagnosis of Clinically Significant Portal Hypertension in Patients with Cirrhosis: Splenic Arterial Resistive Index versus Liver Stiffness Measurement.

    PubMed

    Lee, Chul-Min; Jeong, Woo Kyoung; Lim, Sanghyeok; Kim, Yongsoo; Kim, Jinoo; Kim, Tae Yeob; Sohn, Joo Hyun

    2016-06-01

    The purpose of the present study is to compare the diagnostic accuracy of the splenic arterial resistive index (SARI) with that of liver stiffness measurement (LSM) for identifying patients with clinically significant portal hypertension (CSPH). We included 47 patients (M:F = 37:10) who underwent Doppler ultrasonography, LSM and hepatic venous pressure gradient (HVPG) on the same day. We investigated whether the SARI and LSM were correlated with the HVPG, and compared area under the curve (AUC) values for the abilities of SARI and LSM to diagnose CSPH. We also performed a sub-group analysis. The SARI and LSM were all moderately correlated with HVPG overall in patients. The AUC of SARI and LSM were 0.873 and 0.745, respectively. In patients without splenomegaly, SARI was strongly correlated with HVPG (r = 0.830), but LSM was moderately correlated with HVPG (r = 0.601). The AUC was also higher for SARI than for LSM. Therefore, SARI is potentially an excellent non-invasive measurement method for diagnosing CSPH, especially those without splenomegaly. PMID:27045219

  18. Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension

    PubMed Central

    Kotani, Kohei; Kawabe, Joji; Morikawa, Hiroyasu; Akahoshi, Tomohiko; Hashizume, Makoto; Shiomi, Susumu

    2015-01-01

    The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-β, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism. PMID:26549939

  19. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  20. Oscillatory contractions in tail arteries from genetically hypertensive rats.

    PubMed

    Lamb, F S; Myers, J H; Hamlin, M N; Webb, R C

    1985-01-01

    This study characterizes a cellular mechanism for oscillatory contractions induced by norepinephrine in vascular smooth muscle from spontaneously hypertensive stroke prone rats (SHRSP). Helically cut strips of tail arteries from SHRSP and normotensive Wistar-Kyoto rats (WKY) were mounted in a muscle bath for measurement of isometric force generation. Norepinephrine-induced responses of arteries from SHRSP were characterized by fluctuations in contractile activity, whereas those in arteries from WKY remained constant with time. The magnitude of the oscillatory contractile activity (frequency X mean amplitude) varied directly with norepinephrine concentration (5.9 X 10(-9) to 1.8 X 10(-7) M). The oscillatory contractile activity varied inversely with the potassium concentration (3-20 mM) of the buffer solution and directly with the calcium concentration (0.1-5.0 mM) of the buffer solution. The oscillatory activity was converted to maintained contraction by barium (10(-4) M), quinidine (3 X 10(-6) M), sparteine (10(-3) M), D-600 (10(-7) M), and nifedipine (10(-8) M). Tetraethylammonium and 3,4-diaminopyridine, inhibitors of voltage-dependent potassium channels, did not alter the oscillatory contractile activity induced by norepinephrine. These observations suggest that oscillatory contractile activity in tail arteries from SHRSP is caused by an abnormal variation in potassium efflux during stimulation with norepinephrine. The altered potassium efflux appears to be related to calcium entry, which is sensitive to inhibition by channel blockers. This altered membrane property may contribute to changes in vascular sensitivity in hypertension. PMID:3997233

  1. A blueberry enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Background: Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-indu...

  2. Correction of Hypertension by Normalization of Endothelial Levels of Fibroblast Growth Factor and Nitric Oxide Synthase in Spontaneously Hypertensive Rats

    NASA Astrophysics Data System (ADS)

    Cuevas, Pedro; Garcia-Calvo, Margarita; Carceller, Fernando; Reimers, Diana; Zazo, Mercedes; Cuevas, Begona; Munoz-Willery, Isabel; Martinez-Coso, Victoria; Lamas, Santiago; Gimenez-Gallego, Guillermo

    1996-10-01

    Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension.

  3. Action of polygodial on agonist-induced contractions of the rat portal vein in vitro.

    PubMed

    El Sayah, M; Filho, V C; Yunes, R A; Malheiros, A; Calixto, J B

    2000-04-01

    This study investigated the vasorelaxant action of the sesquiterpene polygodial, isolated from the bark of Drymis winteri, on rat portal vein in vitro, contracted by various agonists. Polygodial (21-342 microM) preincubated 20 min before, produced graded antagonism of the contractile responses caused by bradykinin, endothelin-1, noradrenaline, the stable analogue of thromboxane A2 U46619, substance P, neurokinin B, and senktide (an NK3-selective agonist). Polygodial, at the same concentration, also produced graded inhibition of the contractile response induced by potassium chloride and by phorbol ester. At the median inhibitory concentration (IC50) level, polygodial was approximately 114- to 177-fold more active in inhibiting mediated contractions to senktide and phorbol ester. When assessed in the tonic contraction induced by endothelin-1 (0.5 nM) or by phorbol (3 microM), polygodial (0.1-100 microM) produced concentration-dependent relaxation, with maximal inhibition (E(max)) of 62 +/- 2% and 100%, respectively. Finally, polygodial (0.1-100 microM) inhibited the rhythmic spontaneous contractions of the rat portal vein (E(max) of 75 +/- 2%). Taken together, these results suggest that the vasorelaxant actions caused by polygodial in rat portal vein are, at least in part, associated with inhibition of calcium influx through voltage-sensitive channels and interaction with protein kinase C-dependent mechanisms. In addition, these data confirm and extend our previous suggestion that polygodial preferentially antagonizes tachykinin-mediated contraction, especially the NK3-mediated responses. PMID:10774800

  4. INCREASED SUSCEPTIBILITY OF THE SPONTANEOUSLY HYPERTENSIVE RAT TO CHLORPYRIFOS, AN ORGANOPHOSPHATE PESTICIDE.

    EPA Science Inventory

    Hypertension and hypothermia are common symptoms in rats exposed to chlorpyrifos (CHP), an organophosphate (OP)-based pesticide. CHP inhibits acetylcholinesterase (AChE) activity resulting in central and peripheral stimulation of cholinergic pathways involved in blood pressure ...

  5. Insight into molecular mechanisms of ultrafine carbon particle induced cardiovascular impairments in spontaneously hypertensive rats.

    EPA Science Inventory

    Rationale: Exposure to ambient particulate matter is a risk factor for cardiopulmonary disease as identified in several epidemiological studies. Radio telemetric analysis detected increased heart rate and blood pressure in Spontaneously Hypertensive Rats (SHR) following inhalatio...

  6. Hypotensive effect of the nitrosyl ruthenium complex nitric oxide donor in renal hypertensive rats.

    PubMed

    de Gaitani, Cristiane Masetto; de Melo, Miriam C C; Lunardi, Claure N; de S Oliveira, Fabiana; da Silva, Roberto S; Bendhack, Lusiane M

    2009-05-01

    We have described a new compound (trans-[RuCl([15]aneN(4))NO](2+)), which in vitro releases NO by the action of a reducing agent such as catecholamines. We investigated the effect of this NO donor in lowering the mean arterial pressure (MAP) in severe and moderate renal hypertensive 2K-1C rats. MAP was measured before and after intravenous in bolus injection of the compound in conscious 2K-1C and normotensive (2K) rats. In the hypertensive rats (basal 196.70+/-8.70mmHg, n=5), the MAP was reduced in -34.25+/-13.50mmHg (P<0.05) 6h after administration of 10mmol/L/Kg of the compound in bolus. In normotensive rats the compound had no effect. We have also studied the effect of the injection of 0.1mmol/L/Kg in normotensive (basal 118.20+/-11.25mmHg, n=4), moderate (basal 160.90+/-2.30mmHg, n=6), and severe hypertensive rats (basal 202.46+/-16.74 mmHg, n=6). The compound at the dose of 0.1mmol/L/Kg did not have effect (P>0.05) on MAP of normotensive and moderate hypertensive rats. However, in the severe hypertensive rats (basal 202.46+/-16.70mmHg, n=6) there was a significant reduction on the MAP of -28.64+/-12.45mmHg. The NO donor reduced the MAP of all hypertensive rats in the dose of 10mmol/L/Kg and in the severe hypertensive rats at the dose of 0.1mmol/L/Kg. The compound was not cytotoxic to the rat aortic vascular smooth muscle cells in the concentration of 0.1mmol/L/Kg that produced the maximum relaxation. PMID:19114114

  7. Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

    PubMed

    Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

    2015-11-01

    Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. PMID:26342194

  8. Does Methylphenidate Affect Cystometric Parameters in Spontaneously Hypertensive Rats?

    PubMed Central

    Kim, Khae Hawn; Jung, Ha Bum; Choi, Don Kyoung; Park, Geun Ho; Cho, Sung Tae

    2015-01-01

    Purpose: Methylphenidate (MPH) is one of the most commonly prescribed psychostimulants for attention deficit hyperactivity disorder (ADHD). However, there is limited research on its effects on lower urinary tract function. This study investigated changes in cystometric parameters after intragastric administration of MPH in conscious spontaneously hypertensive rats (SHRs), an animal model of ADHD. Methods: Fourteen- to 16-week-old male SHRs (n=10), weighing between 280 and 315 g, were used. Three micturition cycles were recorded before administering MPH. One hour after each intragastric MPH injection, three cycles of cystometrogram were obtained in the awake condition. Various cystometric parameters were evaluated, including basal pressure (BP), maximal pressure (MP), threshold pressure (TP), bladder capacity (BC), micturition volume (MV), micturition interval (MI), and residual volume (RV). The data were analyzed using paired Student t-tests. Results: Five SHRs were each administered a dose of 3-mg/kg MPH, and the other five received a dose of 6-mg/kg MPH. BP and MP increased significantly in the rats that received the 3-mg/kg MPH injection, but not in those that received the 6-mg/kg injection. BC, MV, and MI significantly increased in the rats that received the 6-mg/kg MPH injection, but not in those that received the 3-mg/kg injection. There were no significant changes in TP after either injection. Conclusions: Significant increases in BC, MV, and MI after the 6-mg/kg MPH injection suggest that the peripheral and the central nervous systems may play important roles in bladder function in those receiving MPH for ADHD. PMID:26126435

  9. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

    PubMed Central

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

  10. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model.

    PubMed

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang; Wu, Shengli

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200-300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p < 0.05). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290