Premen, A.J.; Banchs, V.; Go, V.L.W.; Benoit, J.N.; Granger, D.N.
In anesthetized sham-operated control (C) and portal vein stenosed (PVS) rats, renal blood flow (RBF) was measured with radioactive microspheres on days 2, 4, 6, 8, and 10 following surgery. On day 2, only a small increase in RBF (19%) was produced in PVS versus C rats. However, by day 4, a significant increase in RBF (35%) was observed in PVS versus C animals. By day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than in C rats. Thereafter (on days 8 and 10), the renal hyperemia remained at the maximal value. In a separate group of 10-day PVS rats, glucagon antiserum failed to attenuate the 44% increase in RBF observed in PVS versus C rats. Radioimmunoassay of C and PVS plasma (10-day samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin/gastrin, neurotensin, pancreatic polypeptide, beta-endorphin, and peptide histidine-isoleucine amide are not elevated in arterial plasma of PVS rats. These data indicate that the renal hyperemia induced by chronic portal hypertension is manifested within 4 days after the hypertensive insult. Our studies also suggest that at least 9 blood-borne gastrointestinal peptides are not directly involved in the renal response to portal vein stenosis.
Portal hypertension is the main complication of cirrhosis and is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow, which in turn is the result of splanchnic vasodilatation. Vasodilatation (splanchnic and systemic) and hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which is, in turn, secondary to vasodilatation and activation of neurohumoral systems. The hepatorenal syndrome represents the result of extreme vasodilatation with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency that result in the accumulation of neurotoxins in the brain. This paper reviews the recent advances in the pathophysiology and management of the complications of portal hypertension.
Portal hypertension, the main complication of cirrhosis, is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow. Vasodilatation (splanchnic and systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which, in turn, is secondary to vasodilatation and activation of neurohumoral systems. The hepatorenal syndrome represents the result of extreme vasodilatation, with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency that result in the accumulation of neurotoxins in the brain. This review covers the recent advances in the pathophysiology and management of the complications of portal hypertension.
Heinemann, Akos; Schuligoi, Rufina; Lippe, Irmgard T; Stauber, Rudolf E
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.
Wen, Bin; Liang, Jian; Deng, Xin; Chen, Ran; Peng, Peichun
Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO), synthase (NOS), and endothelin-1 (ET-1) of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P < 0.05 versus baseline). The fluid shear stress declined from week 4 onwards (P < 0.01 versus control group). NO, NOS, and ET-1 increased after repeated CCI4 injections. Hematoxylin and eosin staining showed thickened portal vein walls, with increased inside and outside diameters. Electron microscopy revealed different degrees of endothelial cell degeneration, destruction of basement membrane integrity, proliferating, and hypertrophic smooth muscle cells. Conclusions. Fluid shear stress not only influenced the biomechanical environment of the portal vein but also participated in vascular remodeling.
Cummings, S. A.; Groszmann, R. J.; Kaumann, A. J.
Isolated superior mesenteric veins from portal hypertensive rats were 3 to 10 times more sensitive to 5-hydroxytryptamine (5-HT) and 3 times less sensitive to (-)-noradrenaline than veins from sham-operated rats. The sensitivity to vasopressin did not differ in the 2 groups. Ketanserin competitively antagonized the effects of 5-HT in superior mesenteric veins and portal veins with high affinity (KB values 0.1-0.3 nM), as expected for 5-HT2-receptors. The affinity of ketanserin for 5-HT2-receptors was similar in veins from normal, sham-operated or portal-hypertensive rats. Intraportal injections of low doses of 5-HT caused increases in portal pressure which were more pronounced in portal hypertensive rats than in sham-operated rats and were blocked by 0.3 mg kg-1 ketanserin in both groups. Ketanserin 0.3 mg kg-1 did not block the portal pressor response to (-)-noradrenaline in either group of rats. In portal hypertensive rats but not in sham-operated rats, 0.3 mg kg-1 ketanserin caused decreases in portal pressure, portal flow and cardiac output, as estimated by radioactive microspheres. The reduction in portal pressure caused by ketanserin was due mainly to a decrease in portal venous inflow secondary to a decreased cardiac output. The reduction in cardiac output, which was observed only in the portal hypertensive rats but not in sham-operated rats, is consistent with venous dilatation and pooling of blood in the portal venous system. The venous pooling could be secondary to the blockade of 5-HT2-receptors in the portal venous system. It is proposed that ketanserin should be explored for the treatment of patients with portal hypertension. PMID:3801785
... Affairs, Sidney Kimmel Medical College at Thomas Jefferson University Get the Quick Facts For this topic NOTE: ... at least 6 months) Drinking large amounts of alcohol over a long period of time Portal hypertension ...
Portal hypertension is the main complication of cirrhosis and is responsible for its most common complications: variceal hemorrhage, ascites, and portosystemic encephalopathy. Portal hypertension is the result of increased intrahepatic resistance and increased portal venous inflow. Vasodilatation (splanchnic and systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and portal hypertension. Gastroesophageal varices result almost solely from portal hypertension, although the hyperdynamic circulation contributes to variceal growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium retention, which is in turn secondary to vasodilatation and activation of neurohumoral systems. Hepatic hydrothorax results from the passage of ascites across the diaphragm and into the pleural space. The hepatorenal syndrome represents the result of extreme vasodilatation with an extreme decrease in effective blood volume that leads to maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous bacterial peritonitis is a potentially lethal infection of ascites that occurs in the absence of a local source of infection. Portosystemic encephalopathy is a consequence of both portal hypertension (shunting of blood through portosystemic collaterals) and hepatic insufficiency resulting in the accumulation of neurotoxins in the brain.
Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka; Schierwagen, Robert; Uschner, Frank Erhard; Strassburg, Christian P.; Fischer, Hans-Peter; Spengler, Ulrich; Trebicka, Jonel
Background Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared it to human NCIPH. Methods Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one week after last embolization), hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in patients with NCIPH. Results Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. Discussion This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies. PMID:27589391
Sikuler, E.; Kravetz, D.; Groszmann, R.J.
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).
RODRIGUES, Daren Athiê Boy; da SILVA, Aline Riquena; SERIGIOLLE, Leonardo Carvalho; FIDALGO, Ramiro de Sousa; FAVERO, Sergio San Gregorio; LEME, Pedro Luiz Squilacci
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
Aller, M A; Vara, E; García, C; Méndez, M; Méndez-López, M; Mejía, I; López, L; Arias, J L; Arias, J
Oxidative stress has been reported as a key pathogenic factor in many human liver diseases and in experimental models of cirrhosis related to hepatotoxin administration. The aim of this study was to verify the hypothesis that prehepatic portal hypertension aggravates the enterohepatic redox imbalance in thioacetamide-cirrhotic rats. Wistar male rats were used: Control (n=9); rats with prehepatic portal hypertension by triple partial portal vein ligation (TPVL; n=9); thioacetamide-cirrhotic rats (TAA; n=9) and TPVL-rats associated to TAA administration (TPVL+TAA; n=9). Three months after the operation, portal pressure (PP), mesenteric venous vasculopathy (MVV) and portosystemic collateral circulation were studied. Liver and ileal levels of malondialdehyde (MDA), as a lipid peroxidation marker, and catalase (CAT), glutathione peroxidase (GSH-Px), glutathione transferase (GSH-t) and cytosolic and mitochondrial superoxide dismutases (cSOD and mSOD), as antioxidative enzymatic mechanisms, were measured. Liver and ileal MDA increased in all the experimental groups, although the higher increase occurred in the ileum of rats with portal hypertension. CAT levels decreased in the liver and the ileum in the three experimental groups. The decrease in liver and ileal GSH-Px and GSH-t was greater in rats with portal hypertension, alone or associated with TAA. mSOD activation was demonstrated in the liver when portal hypertension was added to TAA. On the contrary, this compensatory response was not activated in the ileum, where mSOD was significantly decreased. Prehepatic portal hypertension by triple partial portal vein ligation impaired the enterohepatic antioxidative activity and aggravated the intestinal oxidative stress in thioacetamide-cirrhotic rats.
Zhao, Xin; Dou, Jian; Gao, Qing-Jun
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
Zhao, Xin; Dou, Jian; Gao, Qing-Jun
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.
Zhao, Xin; Jia, Hongmei; Yang, Shijun; Liu, Yuetao; Deng, Bo; Xu, Xueyan; Zhang, Tao; Zhou, Hang; Zu, Chengzhe; Yin, He; Li, Ting; Song, Yijun; Wang, Yueqi; Li, Pengtao; Zou, Zhongmei; Cai, Dayong
This study is aimed to investigate the effects of Sal B on portal hypertension (PH). PH with chronic hepatitis was induced by carbon tetrachloride (CCl4) in rats. The model was confirmed with elevated portal pressures and increased serum CD163 levels. The inducible nitric oxide synthase (iNOS) or heme oxygenase-1 (HO-1) in portal triads was assessed. The isolated portal perfused rat liver (IPPRL) was performed at d0, d28, d56 , and d84 in the progression of chronic hepatitis. After constricting with phenylephrine, the portal veins were relaxed with Sal B. The EC50 of Sal B for relaxing portal veins was −2.04 × 10−9, 7.28 × 10−11, 1.52 × 10−11, and 8.44 × 10−11 mol/L at d0, d28, d56, and d84, respectively. More macrophages infiltrated in portal triads and expressed more iNOS or HO-1 as PH advanced. The areas under the curve (AUCs) of Sal B for reducing PH were positively correlated with the levels of iNOS or HO-1 in portal triads, and so did with serum CD163 levels. Sal B reduces PH in IPPRL with chronic hepatitis, via promoting portal relaxation due to macrophage-originated NO or CO in portal triads, partly at least. PMID:23118797
Ahmed, Ahmed F.; El-Maraghy, Nabila N.; Ghaney, Rasha H. Abdel; Elshazly, Shimaa M.
Background/Aim: Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats. Settings and Design: Wister male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days. Patients and Methods: Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state. Results: Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes. Conclusions: captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level. PMID:22626797
Aller, Maria Angeles; Vara, Elena; Garcia, Cruz; Palma, Maria Dolores; Arias, Jorge L.; Nava, Maria Paz; Arias, Jaime
Proinflammatory (TNF-α, IL-1β, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-α, IL-1β, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF-α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL-1β: 19.17 ± 2.87 versus 5.96 ± 1.84 pmol/mg protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30 nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59 pmol/mL; P = .005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed. PMID:16030393
Kamikado, Chiaki; Shibamoto, Toshishige; Zhang, Wei; Kuda, Yuhichi; Ohmukai, Chieko; Kurata, Yasutaka
Anaphylactic shock in rats is characterized by antigen-induced hepatic venoconstriction and the resultant portal hypertension. We determined the role of portal hypertension in anaphylactic hypotension by using the side-to-side portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We measured the mean arterial blood pressure (MAP), portal venous pressure (PVP), and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous breathing. Anaphylactic hypotension was induced by an intravenous injection of ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103 mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the antigen. In the portacaval shunt rats, in response to the antigen, PVP increased slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease, and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These results suggest that the portacaval shunt attenuated anaphylactic portal hypertension and venous return decrease, partially preventing anaphylactic hypotension. In conclusion, portal hypertension is involved in rat anaphylactic hypotension presumably via splanchnic congestion resulting in decreased venous return and thus systemic arterial hypotension.
Aller, Maria-Angeles; Vara, Elena; García, Cruz; Nava, Maria-Paz; Angulo, Alejandra; Sánchez-Patán, Fernando; Calderón, Ana; Vergara, Patri; Arias, Jaime
AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides, diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis. PMID:17106932
Migoh, S; Hashizume, M; Tsugawa, K; Tanoue, K; Sugimachi, K
The aim of this study was to determine the role of endothelin (ET)-1 in portal hypertensive gastropathy (PHG) under portal hypertension, in order to investigate whether the ET(A/B) receptor inhibitor improves the permeability of gastric mucosal microvessels in PHG. Portal hypertensive rats (PVL) and sham-operated rats (CTR) were prepared and then the concentration of plasma ET-1 was measured and the vasopressor response to ET-1 was compared between the two groups. The plasma ET-1 levels in PVL increased significantly compared with CTR; however, the vasopressor response to ET-1 in PVL decreased more than in CTR. Next, the portal venous pressure was measured in both CTR and PVL pretreated with or without a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), before the injection of ET-1. The portal venous pressure of PVL after receiving ET-1 and being pretreated with L-NAME significantly increased in comparison to the pressure of PVL treated with ET-1 alone (without L-NAME). Moreover, Evans-Blue was injected into each rat and the absorbancy of the gastric contents was measured. The absorbancy of Evans-Blue in PVL increased significantly compared with CTR; however, the absorbancy in PVL+ ET(A/B) receptor inhibitor (Ro47-0203) decreased significantly more than in PVL. This study showed that ET-1 is a potent vasoconstrictive substance that also has a transitory vasodilative response through NO induced by ET-1 in portal hypertension. In addition, it was found that the vascular permeability of the gastric mucosa increased in portal hypertension and that Ro47-0203 inhibited the hyper-permeability. Accordingly, ET-1 may, thus, play an important role in the development of PHG through NO induced by ET-1. Ro47-0203 may, therefore, be a useful substance for improving PHG in portal hypertension.
Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K
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.
Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K
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
de Las Heras, Natalia; Aller, María-Angeles; Martín-Fernández, Beatriz; Miana, María; Ballesteros, Sandra; Regadera, Javier; Cachofeiro, Victoria; Arias, Jaime; Lahera, Vicente
Long-term prehepatic portal hypertension in the rat produces a low-grade splanchnic inflammation with liver steatosis and dyslipidemia. It has been suggested that in this experimental model these inflammatory alterations could represent a risk factor of vascular disease. Therefore, our aim was to investigate whether long-term prehepatic portal hypertension (PH) induces vascular pathology, fundamentally inflammatory aortopathy. Male Wistar sham-operated (SO) rats and rats with triple partial portal vein ligation in the very long-term (22 months) of postoperative evolution were used. Serum lipid profile, pro- and anti- inflammatory cytokines and ACTH and corticosterone were assayed by spectrophotometric and ELISA techniques. Aorta mRNA expression of oxidative and nitrosative stress enzymes, NFκB e IκB, immune-related cytokine production and vascular fibrosis parameters, were evaluated by real time RT-PCR. In addition, aortic p22phox subunit immunostaining, morphometry and vascular fibrosis in aorta were analyzed. PH rats have increased serum cholesterol, triglyceride, low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), while high-density lipoproteins (HDL) were lower than in SO rats. Serum ACTH and corticosterone decreased in PH rats. Also, serum TNF-α, IL-1β and IL-6 were significantly higher in PH-rats. Portal hypertensive-rats showed aortic oxidative stress with increased mRNA expressions of NAD(P)H oxidase p22phox, XDh, SOD and eNOS; higher aortic levels of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6; remodeling markers, like collagen I, CTGF and MMP-9; and finally, higher protein production of p22phox and collagen and extracellular matrix density were significantly higher in rats with PH. The results from the current study suggest that very long-term prehepatic portal hypertension in rats induces an abdominal aortic inflammatory and fibrotic response. Therefore, it could be considered that portal hypertension aggravates
Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong
Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism.
Liang, Jian; Deng, Xin; Lin, Zhi-Xiu; Zhao, Li-Chun; Zhang, Xi-Liu
AIM: To investigate the inhibitory effect of natural taurine (NTau) on portal hypertension (PHT) in rats with experimentally-induced liver cirrhosis (LC). METHODS: Experimentally-induced LC Wistar rats (20 rats/group) were treated with either oral saline or oral NTau for 6 consecutive weeks. Evaluation parameters included portal venous pressure (PVP), portal venous resistance (PVR), portal venous flow (PVF), splanchnic vascular resistance (SVR) and mean arterial pressure (MAP). Vasoactive substance levels including nitric oxide (NO), nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were also measured. Histological investigation of type I and III collagen (COL I and III) and transforming growth factor-β1 (TGF-β1) was also performed. RESULTS: Treatment with NTau (1) significantly decreased PVP, PVR and PVF, and increased MAP and SVP; (2) markedly increased the vascular compliance and reduced the zero-stress of the portal vein; (3) markedly decreased the amount of NO and cGMP and activity of NOS; and (4) improved the pathological status of the liver tissue and reduced the expression of COL I, COL III and TGF-β1. CONCLUSION: NTau inhibited the LC-induced PHT by improving hyperdynamic circulation, morphology of liver and biomechanical properties of the portal vein in experimentally-induced LC rats. PMID:19777611
Fortea, José I; Zipprich, Alexander; Fernandez-Mena, Carolina; Puerto, Marta; Bosoi, Cristina R; Almagro, Jorge; Hollenbach, Marcus; Bañares, Juan; Rodríguez-Sánchez, Belén; Cercenado, Emilia; Clément, Marc-André; Rose, Christopher F; Bañares, Rafael; Vaquero, Javier; Ripoll, Cristina
Recent studies suggest that heparins reduce liver fibrosis and the risk of decompensation of liver disease. Here, we evaluated the effects of enoxaparin in several experimental models of advanced cirrhosis. Cirrhosis was induced in male Sprague-Dawley (SD) rats by: i. Oral gavage with carbon tetrachloride (CCl4ORAL ), ii. Bile duct ligation (BDL), and iii. CCl4 inhalation (CCl4INH ). Rats received saline or enoxaparin s.c. (40 IU/Kg/d or 180 IU/Kg/d) following various protocols. Blood biochemical parameters, liver fibrosis, endothelium- and fibrosis-related genes, portal pressure, splenomegaly, bacterial translocation, systemic inflammation, and survival were evaluated. Endothelial dysfunction was assessed by in-situ bivascular liver perfusions. Enoxaparin did not ameliorate liver function, liver fibrosis, pro-fibrogenic gene expression, portal hypertension, splenomegaly, ascites development and infection, serum IL-6 levels or survival in rats with CCl4ORAL or BDL-induced cirrhosis. Contrarily, enoxaparin worsened portal pressure in BDL rats and decreased survival in CCl4ORAL rats. In CCl4INH rats, enoxaparin had no effects on hepatic endothelial dysfunction, except for correcting the hepatic arterial dysfunction when enoxaparin was started with the CCl4 exposure. In these rats, however, enoxaparin increased liver fibrosis and the absolute values of portal venous and sinusoidal resistance. Our results do not support a role of enoxaparin for improving liver fibrosis, portal hypertension or endothelial dysfunction in active disease at advanced stages of cirrhosis. These disease-related factors and the possibility of a limited therapeutic window should be considered in future studies evaluating the use of anticoagulants in cirrhosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Zhao, Xin; Deng, Bo; Xu, Xue-Yan; Yang, Shi-Jun; Zhang, Tao; Song, Yi-Jun; Liu, Xiao-Ting; Wang, Yue-Qi; Cai, Da-Yong
AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage
Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.
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
Coll, Mar; Genescà, Joan; Raurell, Imma; Rodríguez-Vilarrupla, Aina; Mejías, Marc; Otero, Teresa; Oria, Marc; Esteban, Rafael; Guardia, Jaime; Bosch, Jaime; Martell, María
Splanchnic vasodilation initiates the hyperdynamic syndrome in portal hypertension. We aimed to explore molecular mechanisms involved in the development of mesenteric vasodilation in portal hypertension. Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models. Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively. Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.
Wang, Dong; Wang, Qin; Yin, Jikai; Dong, Rui; Wang, Qing; Du, Xilin; Lu, Jianguo
AG490, the specific inhibitor of JAK2/STAT3 signaling, has been shown to decrease portal pressure, splanchnic hyperdynamic circulation and liver fibrosis in cirrhotic rats. Nonselective betablockers such as propranolol are the only drugs recommended in the treatment of portal hypertension. The aim of this study was to explore the combinative effect of treatment with propranolol and AG490 on portal hypertension. Rats induced by common bile duct ligation were treated with vehicle, AG490, propranolol, or AG490 + propranolol for 2 weeks. Hemodynamics parameters were assessed. Expressions of phospho-STAT3 protein and its down-regulated cytokines in splanchnic organs were detected by ELISA or western blot. Lipopolysaccharide binding protein (LBP) and IL-6 were assessed by ELISA or western blot. Characterization of liver and mesentery was performed by histological analyses. Highly expressed phospho-STAT3 protein in cirrhotic rats could successfully be inhibited by AG490 or AG490 + propranolol treatments but not by propranolol alone. Both AG490 and propranolol significantly reduced portal pressure and hyperdynamic splanchnic circulation, and combination of AG490 and propranolol achieved an additive effect than with either drug alone. AG490, alone or in combination with propranolol, inhibited liver fibrosis, splenomegaly and splanchnic angiogenesis. Increased markers of bacterial translocation (LBP and IL6) were greatly reduced by propranolol but not by AG490. The combination of propranolol and AG490 caused a greater improvement of portal hypertension and might therefore offer a potentially promising therapy in the portal hypertension treatment. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Wang, Mofei; Tanida, Mamoru; Shibamoto, Toshishige; Kurata, Yasutaka
Anaphylactic shock is sometimes life-threatening, and it is accompanied by hepatic venoconstriction in animals, which, in part, accounts for anaphylactic hypotension. Roles of norepinephrine and α-adrenoceptor in anaphylaxis-induced hypotension and portal hypertension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups (n = 6/group): 1) control (nonpretreatment), 2) α1-adrenoceptor antagonist prazosin, 3) nonselective α-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was induced by an intravenous injection of the antigen. The systemic arterial pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAP-PVP)/PBF] and portal venous [Rpv: (PVP-CVP)/PBF] resistances were determined. Separately, we measured efferent hepatic sympathetic nerve activity during anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. PVP and Rpv increased 3.2- and 23.3-fold, respectively, after antigen. Rspl decreased immediately, but only transiently, after antigen, and then increased 1.5-fold later than 10 min. The α-adrenoceptor antagonist pretreatment or chemical sympathectomy inhibited the late increase in Rspl and the SAP recovery. Pretreatment with α-adrenoceptor antagonists, or either chemical or surgical hepatic sympathectomy, did not affect the antigen-induced increase in Rpv. Hepatic sympathetic nerve activity did not significantly change after antigen. In conclusion, α-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved in anaphylactic portal hypertension.
Bomzon, A; Jacob, G; Lee, S S; Meddings, J
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.
Mousavi, Seyyedeh Elaheh; Rezayat, Seyed Mahdi; Nobakht, Maliheh; Saeedi Saravi, Seyed Soheil; Yazdani, Iraj; Rashidian, Amir; Dehpour, Ahmad Reza
Objective(s): An increase in nitric oxide (NO) production has been reported in cirrhotic cardiomyopathy and, portal hypertension. Since minocycline has been shown to inhibit NO overproduction, we aimed to examine its role in a rat model of CCl4-induced cirrhotic cardiovascular complications. Materials and Methods: Portal pressure and inotropic responsiveness of isolated papillary muscles to isoproterenol were measured in cirrhotic rats, following minocycline (50 mg/kg/day for 8 weeks) treatment. Moreover, isolated papillary muscles were incubated with nonselective and selective nitric oxide synthase (NOS) inhibitors, N (ω)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) respectively, in an organ bath. Ventricular expression and localization of inducible NOS (iNOS), tumor necrosis factor-alpha (TNF-α) and serum nitrite concentration were evaluated. Results: We found a decreased portal hypertension in minocycline-treated cirrhotic rats. Cirrhosis decreased contractility in response to isoproterenol stimulation, which was significantly attenuated by minocycline. Incubation with either L-NAME or AG reversed the impaired contractility in cirrhotic rats. Furthermore, minocycline decreased iNOS expression and localization in cardiomyocytes. A drop in serum nitrite and cardiac TNF-α level were also observed in cirrhotic rat that were treated by minocycline. Conclusion: The results suggest that minocycline may improve impaired cardiac contractility and hyperdynamic state in cirrhotic rats, and this effect could be mediated by NO-dependent mechanism. PMID:27917279
Evelson, P; Llesuy, S; Filinger, E; Rodriguez, R R; Lemberg, A; Scorticati, C; Susemihl, M; Villareal, I; Polo, J M; Peredo, H; Perazzo, J C
1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was designed to investigate the occurrence of OS in prehepatic PH rat livers following the induction of diabetes. 2. Five groups of rats were used: control, sham operated, chronic diabetes (induced with a single dose of streptozotocin at 60 mg/kg, i.p.), prehepatic PH and chronic diabetic plus prehepatic PH. The occurrence of OS was determined in liver homogenates by measuring hydroperoxide-initiated chemiluminescence and the activity of anti-oxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). 3. Prehepatic PH produced a significant increase in hydroperoxide-initiated chemiluminescence in the liver compared with control and sham-operated rats, whereas the liver in chronic diabetic rats showed no difference. However, chemiluminescence values decreased almost by 50% in the chronic diabetic plus prehepatic PH group. Concomitantly, the activities of the anti-oxidant enzymes in chronic diabetes, prehepatic PH and chronic diabetic plus prehepatic PH groups were decreased (P < 0.05 vs control and sham-operated groups). 4. Livers from the chronic diabetic group did not show any evidence of the occurrence of OS, whereas the prehepatic PH group showed the occurrence of OS. The association of PH and chronic diabetes resulted in a significant decrease in the occurrence of OS, which could be explained by an anti-oxidant response to an OS.
Fernández-Varo, Guillermo; Oró, Denise; Cable, Edward Earl; Reichenbach, Vedrana; Carvajal, Silvia; de la Presa, Bernardino González; Wiśniewski, Kazimierz; Ginés, Pere; Harris, Geoffrey; Jiménez, Wladimiro
Patients and rats with cirrhosis and ascites have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. We assessed the potential therapeutic value of a new V1 a -AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE 204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE 204038, terlipressin, or vehicle were investigated. Mean arterial pressure and PP were continuously recorded and cardiac output and systemic vascular resistance (SVR) assessed at 30-minute intervals for 90 minutes. Urine volume, urine osmolality, and urinary excretion of sodium and creatinine were measured in basal conditions and following twice-daily subcutaneous doses of FE 204038 or vehicle. PP, mean arterial pressure, cardiac output, SVR, and ascites volume were also measured after 6 days. The expression of an array of vasoactive genes was assessed in the thoracic aorta and the mesenteric circulation of control rats and rats with cirrhosis and ascites. FE 204038 dose-dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V1a -AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE 204038. V1a -AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. FE 204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V1a -AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis. © 2015 by the
Hesdorffer, C.S.; Bezwoda, W.R.; Danilewitz, M.D.; Esser, J.D.; Tobias, M.
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.
Todd, M E
The portal vein was investigated in male spontaneously hypertensive rats (SHR), from Wistar-Kyoto (WKY) and Wistar strains, in animal 16-20 weeks old. In SHR, the inner circular smooth muscle was unchanged, but the outer longitudinal layer showed marked alterations in shape and size, readily observed in three-dimensional micrographs using scanning electron microscopy. The cells in both Wistar and WKY were elongate and tubular with little variation along their lengths and with a relatively smooth sarcolemma. This applied to both the inner and outer layers of smooth muscle. In contrast, the smooth muscle cells from SHR in the outer layer varied considerably in thickness along their lengths, and had very irregular outlines with numerous pits or depressions of varying sizes. In addition, the cells frequently had major forks or branches. The vasa vasorum running through the muscle layer, fibroblasts and nerve bundles were also identified. Sectioned material (transmission electron microscopy) showed a change in shape and hypertrophy of the smooth muscle cells from the portal vein of SHR, and also demonstrated a significant increase in paracellular connective tissue in the outer layer of smooth muscle. Such major morphological alterations in the outer layer of smooth muscle in the portal vein from SHR could have profound effects on functional studies.
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
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
Aller, María-Angeles; Arias, Jorge-Luis; Cruz, Arturo; Arias, Jaime
Background Portal hypertension is a clinical syndrome that manifests as ascites, portosystemic encephalopathy and variceal hemorrhage, and these alterations often lead to death. Hypothesis Splanchnic and/or systemic responses to portal hypertension could have pathophysiological mechanisms similar to those involved in the post-traumatic inflammatory response. The splanchnic and systemic impairments produced throughout the evolution of experimental prehepatic portal hypertension could be considered to have an inflammatory origin. In portal vein ligated rats, portal hypertensive enteropathy, hepatic steatosis and portal hypertensive encephalopathy show phenotypes during their development that can be considered inflammatory, such as: ischemia-reperfusion (vasodilatory response), infiltration by inflammatory cells (mast cells) and bacteria (intestinal translocation of endotoxins and bacteria) and lastly, angiogenesis. Similar inflammatory phenotypes, worsened by chronic liver disease (with anti-oxidant and anti-enzymatic ability reduction) characterize the evolution of portal hypertension and its complications (hepatorenal syndrome, ascites and esophageal variceal hemorrhage) in humans. Conclusion Low-grade inflammation, related to prehepatic portal hypertension, switches to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. PMID:17999758
Aller, Maria-Angeles; de las Heras, Natalia; Nava, Maria-Paz; Regadera, Javier; Arias, Jaime; Lahera, Vicente
Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension. PMID:24307792
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
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.
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
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
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
To evaluate the antioxidant effect of N-acetylcysteine (NAC) on the stomach of rats with portal hypertension. 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 15(th) day the animals were anesthetized and we evaluated portal pressure by cannulating mesenteric artery. After, we removed the stomach for further analysis. We performed immunohistochemical analysis for endothelial nitric oxide synthase (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. 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 eNOS (14.60 ± 4.1 vs 56
Odièvre, M; Pigé, G; Alagille, D
Congenital abnormalities were present in 12 out of 30 (40%) children with extrahepatic portal hypertension of unknown cause, but in only 2 out of 17 (12%) children with extnahepatic portal hypertension secondary to umbilical vein catheterization or omphalitis. The most frequent abnormalities in this series and in published reports were atrial septal defect, malformation of the biliary tract, and anomalous inferior vena cava. These findings are consistent with the view that some cases with extrahepatic portal hypertension are congenital in origin. PMID:869567
Odièvre, M; Pigé, G; Alagille, D
Congenital abnormalities were present in 12 out of 30 (40%) children with extrahepatic portal hypertension of unknown cause, but in only 2 out of 17 (12%) children with extnahepatic portal hypertension secondary to umbilical vein catheterization or omphalitis. The most frequent abnormalities in this series and in published reports were atrial septal defect, malformation of the biliary tract, and anomalous inferior vena cava. These findings are consistent with the view that some cases with extrahepatic portal hypertension are congenital in origin.
Mojtahedzadeh, Mona; Otoukesh, Salman; Shahsafi, Mohammad R.; Tahbaz, Mohammad O.; Rahvari, Seyed K.; Poorabdollah, Mihan; Sajadi, Mohammad M.
In this report, we present a case of isolated liver tuberculosis (TB) as a cause of non-cirrhotic portal hypertension leading to bleeding esophageal varices. Although TB has been known to cause portal hypertension in a variety of ways, this case was notable for the presence of periportal inflammation and granulomas, also seen in hepatic schistosomiasis. Herein, we discuss isolated liver TB and the differential diagnosis of non-cirrhotic portal hypertension. In endemic areas, TB should be considered in the differential diagnosis of non-cirrhotic portal hypertension. PMID:22764308
Scorticati, Camila; Perazzo, Juan C; Rettori, Valeria; McCann, Samuel M; De Laurentiis, Andrea
Since very little is known about neuroendocrine changes that occur in portal-systemic hepatic encephalopathy, we studied plasma prolactin (PRL) levels and the involvement of hyperammonemia, nitric oxide (NO) and dopaminergic and adrenergic systems in the control of this hormone secretion in a male rat model of prehepatic portal hypertension (PH). We conducted in vivo studies to determine plasma ammonia and PRL levels. Dopamine (DA), dihydroxyphenylacetic acid (DOPAC), epinephrine and norepinephrine content in medial basal hypothalamus (MBH) and anterior pituitary (AP) were measured. In addition, NO synthase (NOS) activity and protein expression were evaluated in APs. In in vitro studies, the APs from intact rats were incubated with different doses of ammonia and PRL secretion was determined. In ex vivo studies, the APs from normal and PH rats were incubated in the presence of ammonia and/or a NOS inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME) and PRL secretion was determined. PH rats had a significant increase in plasma ammonia levels (p < 0.001) and a decrease in plasma PRL levels (p < 0.05). Neither DA nor DOPAC content or DOPAC/DA ratios were modified in both MBH and APs; however, we observed a significant increase in norepinephrine content in both MBH and AP (p < 0.001 and p < 0.05, respectively) and a significant increase in epinephrine in APs (p < 0.001). Moreover, PH produced an increase in NOS activity (p < 0.01) and NOS protein expression (p < 0.0001) in APs. The ammonia (100 microM) significantly reduced PRL secretion from APs in vitro (p < 0.05). The presence of L-NAME, an inhibitor of NOS, abrogated the inhibitory effect of ammonia on PRL secretion from APs from control and PH rats. We found that plasma PRL levels were decreased in PH rats probably due to the high ammonia levels. The central noradrenergic system could also mediate this decrease. Also, the increase in NOS activity and/or content in AP induced NO production that directly inhibited
Sastre, Esther; Balfagón, Gloria; Revuelta-López, Elena; Aller, Maria-Ángeles; Nava, Maria-Paz; Arias, Jaime; Blanco-Rivero, Javier
In the present study, we analysed possible alterations in adrenergic, nitrergic and sensory functioning in mesenteric arteries from rats at 1 and 21 months after partial portal vein ligation, and the mechanisms involved in these alterations, if any. For this purpose, we analysed the vasoconstrictor response to EFS (electrical field stimulation) and the effect of the α-antagonist phentolamine, the NOS (nitric oxide synthase) inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester) and the CGRP (calcitonin gene-related peptide) receptor antagonist CGRP-(8-37) in mesenteric segments from ST (short-term; 1 month) and LT (long-term; 21 months) SO (sham-operated) and pre-hepatic PH (portal hypertensive) rats. The vasomotor responses to NA (noradrenaline), the NO donor DEA-NO (diethylamine NONOate) and CGRP were analysed. NA, NO and CGRP releases were measured. Phospho-nNOS (neuronal NOS) expression was studied. The vasoconstrictor response to EFS was decreased in STPH animals. Phentolamine decreased this vasoconstrictor response more strongly in SO animals. Both L-NAME and CGRP-(8-37) increased vasoconstrictor response to EFS more strongly in PH than SO segments. PH did not modify vasomotor responses to NA, DEA-NO or CGRP, but it decreased NA release while increasing those of NO and CGRP. Phospho-nNOS expression was increased by PH. In LTPH, no differences were observed in vasoconstrictor response to EFS, vasomotor responses or neurotransmitter release when compared with age-matched SO animals. In conclusion, the mesenteric innervation may participate in the development of the characteristic hyperdynamic circulation observed in STPH through the joint action of decreased adrenergic influence, and increased nitrergic and sensory innervations influences. The participation of each innervation normalizes under conditions of LTPH.
Rondonotti, Emanuele; Villa, Federica; Dell' Era, Alessandra; Tontini, Gian Eugenio; de Franchis, Roberto
Since the introduction of small bowel capsule endoscopy, and more recently of esophageal capsule endoscopy, these diagnostic tools have become available for the evaluation of the consequences of portal hypertension in the esophagus, stomach, and small intestine. The main advantage of the esophageal and the small bowel capsule is the relatively less invasiveness that could potentially increase patients' adherence to endoscopic screening/surveillance programs. When esophageal capsule endoscopy was compared with traditional gastroscopy, it showed good sensitivity and specificity in recognizing the presence and the size of esophageal varices. However, the results are not consistent among studies, and more data are needed.
Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d’Amati, Giulia
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
Riggio, Oliviero; Gioia, Stefania; Pentassuglio, Ilaria; Nicoletti, Valeria; Valente, Michele; d'Amati, Giulia
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.
Kai, Seiichiro; Ohta, Masayuki; Tominaga, Masayuki; Matsumoto, Toshifumi; Bandoh, Toshio; Kitano, Seigo
Portal hypertensive (PHT) gastropathy has an increased susceptibility to damage due to noxious factors. Heat shock protein (HSP) 72 has a protective effect against gastric mucosal injury and geranylgeranylacetone (GGA) is an inducer of HSP 72. However, it remains unclear how HSP 72 influences the PHT gastric mucosa. The aim of the present study was to investigate HSP 72 induction by GGA and the protective effect to gastric mucosa in PHT rats. PHT rats were produced by staged portal vein occlusion, and GGA 200 mg/kg was orally administered. Expression of HSP 72 protein in the gastric mucosa was evaluated by enzyme-linked immunosorbent assay, and gastric mucosal damage against 70% ethanol (10 mL/kg) following GGA or vehicle treatment was also estimated. Expression of mucosal HSP 72 after vehicle administration was significantly higher in the PHT rats compared with the sham-operated rats. After GGA treatment, portal pressure did not change but HSP 72 was significantly increased in the gastric mucosa of both groups. Ethanol-induced gastric mucosal damage was significantly decreased due to GGA treatment in the PHT rats, but not in the sham-operated rats. These findings suggest that HSP 72 expression is enhanced in PHT gastric mucosa and plays an important role in gastric mucosal protection. The induction of HSP 72 by GGA may therefore effectively prevent mucosal injury in the PHT stomach.
Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong
Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the
Bloom, S; Kemp, W; Lubel, J
Portal hypertension is an important complication of liver disease. As a result of elevated pressures within the portal vein several complications can arise, including the development of oesophageal and gastric varices, ascites, hepatic encephalopathy as well as complications secondary to circulatory dysfunction, such as hepatorenal syndrome, portopulmonary syndrome and hepatopulmonary syndrome. This review outlines the pathogenesis and diagnosis of portal hypertension and outlines the management of these various important clinical sequelae. The management of oesophageal and gastric varices is particularly important, and both the emergency management together with prophylactic management of this condition are described.
Partial splenectomy, transposition of the spleen to the abdominal wall or splenohepatoplasty in portal hypertensive rats. Effects on portal venous pressure and homeostasis--microscopical appearance of the transposed spleen.
Tröbs, R B; Bennek, J
Reduction of the splenic volume by partial resection and collateral development after transposition are of potential value in the elective treatment of esophageal varices, hypersplenism and ascites. A study was performed on young Wistar rats. A simple animal model of extrahepatic portal hypertension was used, narrowing the portal vein to an outer diameter of one millimeter (PVS). One day, three weeks and seven weeks after this operation the portal venous pressure was elevated as compared with the sham-operated controls. The portal hypertension was statistically significant at week three (1.31 +/- 0.04 vs. 0.72 +/- 0.18 kPa, p = 0.01). Portocaval pressure gradient after partial resection of the spleen (SR) and intramuscular transposition (IMTrans) was compared with the pressure gradient after graded portal vein stenosis. Three weeks after intramuscular transposition portocaval pressure gradient was reduced (1.46 +/- 0.38 vs. 1.74 +/- 0.13 kPa, n.s.). This data supports the hypothesis that the portal venous high-pressure compartment and the systemic venous low-pressure compartment are maintained after development of natural shunts to the systemic circulation. In the following experiment different types of splenic transposition were tested and compared to each other and a normal control group or to rats with protal vein stenosis (PVS), respectively. After PVS, the animals were reoperated, an SR was performed and the wound surface of the spleen was transposed into the left abdominal wall subcutaneously (SCTrans) or intramuscularly (IMTrans) or to the left liver lobe (splenohepatoplasty, SHP), respectively. After three weeks the animals underwent measurements of organ weights, collections of blood samples and the spleen was investigated histologically. Blood cell counts were nearly normal but total serum protein, albumin and the colloid osmotic pressure were slightly diminished or significantly reduced (COP in the groups PVS + SR + IMTrans or SCTrans, p < 0.05) compared
Papazian, A; Braillon, A; Dupas, J L; Sevenet, F; Capron, J P
The endoscopic features of the gastric mucosa in patients with cirrhosis have not been systematically investigated. In these patients, we observed an endoscopic aspect, consisting of multiple small erythematous areas, outlined by a subtle yellowish network (resembling a mosaic), mainly located in the proximal part of the stomach. We tested the value of this sign by comparing two groups: 100 patients with portal hypertension due to cirrhosis, and 300 control patients without signs of liver disease or portal hypertension. This endoscopic pattern was observed in 94 of the patients with cirrhosis, whereas oesophageal varices were seen in 78 only. In contrast, only one patient of the control group had this aspect. Moreover, this sign was also found in seven of eight patients with non cirrhotic portal hypertension, but was seen neither in 100 patients with chronic alcoholism but without liver disease, nor in 10 cirrhotic patients with end-to-side portacaval shunts. These endoscopic changes might be because of mucosal and/or submucosal oedema and congestion highlighting the normal areae gastricae pattern and related to raised portal pressure. We conclude that the mosaic pattern of the gastric mucosa is a sensible and specific sign for diagnosis of portal hypertension, whatever the cause. Images Figure PMID:3781334
Kaley, Kristin; Lamb, Lynne
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
Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A
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.
Costaguta, Alejandro; Alvarez, Fernando
Bleeding from esophageal varices is the most severe complication of portal hypertension, and should be managed in specially trained centers. Vasoactive drugs, mainly octreotide, plus endoscopic treatment are able to control bleeding in 90% of the cases. Rescue treatments like TIPS and surgery should be immediately available for those who do not stop bleeding or have varices difficult to manage.
Arai, K; Matsui, O; Kadoya, M; Yoshikawa, J; Gabata, T; Takashima, T; Kobayashi, K; Unoura, M
Magnetic resonance imaging was performed in four patients with biopsy proven idiopathic portal hypertension (IPH). The MR images show proximity of medium-sized intrahepatic vessels to each other and to the liver surface in all patients. Small vessels running parallel to the second order branches of the intrahepatic portal vein are commonly seen as collateral pathways of portal flow in IPH and were seen in two patients. These findings were clearly demonstrated on gradient-recalled echo images. Intrahepatic periportal abnormal high intensity was seen in all patients on T2-weighted images and may reflect abnormalities in the portal tracts such as fibrous enlargement and increase in the number of vascular channels. Tiny low-intensity nodules sometimes observed in liver cirrhosis were not seen in any patient. Magnetic resonance was a useful noninvasive method in the differentiation of IPH from liver cirrhosis.
Snowdon, V. K.; Guha, N.; Fallowfield, J. A.
Portal hypertension is the main cause of complications in patients with cirrhosis. However, evaluating the development and progression of portal hypertension represents a challenge for clinicians. There has been considerable focus on the potential role of noninvasive markers of portal hypertension that could be used to stratify patients with respect to the stage of portal hypertension and to monitor disease progression or treatment response in a longitudinal manner without having to undertake repeated invasive assessment. The pathogenesis of portal hypertension is increasingly understood and emerging knowledge of the vascular processes that underpin portal hypertension has paved the way for exploring novel biomarkers of vascular injury, angiogenesis, and endothelial dysfunction. In this paper we focus on the pathogenesis of portal hypertension and potential non-invasive biomarkers with particular emphasis on serum analytes. PMID:22720166
Orozco, H; Mercado, M A; Takahashi, T; García-Tsao, G; Guevara, L; Hernandez-Ortiz, J; Tielve, M
At the beginning of the seventies, we began to perform regularly selective shunts for the treatment of portal hypertension. In a 15 year period, 177 patients (155 with liver cirrhosis) were operated with three kinds of selective shunts: 128 with a Warren shunt, 29 with an end to end renosplenic shunt and 20 with a splenocaval shunt. 167 cases were operated in an elective fashion. The 15 years global operative mortality, was 14.4%. Operative mortality of the Child A patients, was 11.6%. Survival for the Child A group was 74.6% at 1 year, 68.2% at 5 years and 64.6% at 15 years. Incapacitating encephalopathy was observed in 6.9%, rebleeding 6.2% and shunt thrombosis in 6.2%. Portal vein alterations in the postoperative period were observed: in 13.3% a reduction in diameter ocurred and in 20.5%, thrombosis was recorded. It is concluded that when feasible, the selective shunts are the treatment of choice for portal hypertension in those patients with good liver function.
Koolpe, H A; Koolpe, L
There has been a correlation of three hemodynamic parameters with the etiology of portal hypertension and one of the major determinants of therapeutic success, namely, the direction of portal flow. The presence of a 4 mm Hg or greater gradient between the right atrium and the intrahepatic inferior vena cava associated with a "lumpy" pull-back tracing between the wedged and free positions has been associated with alcoholic liver disease. Such patients have antegrade portal flow when their AoD/HWP ratio is in the range of 2.6 to 2.0, and flow becomes stagnant or reversed below this range. Nonalcoholic liver disease is characterized by the absence of a gradient between the right atrium and the inferior vena cava and by a pull-back tracing that falls smoothly and rapidly to the free hepatic vein value. These patients have antegrade portal flow with an AoD/HWP ratio in the range of 1.7 to 1.5. The correct characterization of the cause for diffuse liver disease and direction of portal flow applies to the selection process for patients being considered for the selective distal splenorenal shunt as well as for the newer procedure of orthotopic liver transplantation. It is hoped that the wider application of these physiologic parameters, in the context of an increasing array of imaging tools for the portal system, including high-resolution ultrasound, computed tomography, and magnetic resonance imaging (MRI), will continue to offer all clinicians interested in the problem of portal hypertension a reliable guide to prognosis and the success of the particular treatment provided.
Arias, Natalia; Méndez, Marta; Arias, Jaime; Arias, Jorge L
Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. The present study was undertaken in order to compare the performance of sham-operated rats (SHAM) and portal hypertension rats (PH) in reference memory tasks in the Morris water maze (MWM). Two groups of animals were used: SHAM group (n=12) was used as a control group and PH group (n=12) by the triple portal vein ligation method was used as an animal model of early evolutive phase of PH. The portal pressure was measured in the splenic parenchyma. Our work shows that spatial learning in the MWM is not impaired in PH group although this group showed a one-day delay in the task acquisition compared to the SHAM group. We assessed the brain metabolic activity of the animals by means of cytochrome c-oxidase (COx) histochemistry. Significant changes were found in the CA3, dentate gyrus, basolateral, medial, lateral and central amygdala, showing lower COx activity in the PH group as compared to the SHAM group in all cases. We found no changes in metabolic activity in prefrontal cortex and CA1 area between groups. In fact, different neural networks were shown according to the execution level of the subjects. The early PH evolution induced changes in brain metabolic activity without biggest alterations in spatial memory.
Schimpl, G; Pabst, M; Feierl, G; Kuesz, A; Ozbey, H; Takahashi, S; Hollwarth, M
BACKGROUND—Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function. AIM—To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO. METHODS—Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. RESULTS—Significant (p<0.01) intestinal bacterial overgrowth was present in all PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0.05). Tungsten treatment completely suppressed jejunal XD and XO activities. CONCLUSIONS—Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting
Hirota, Shozo; Ichikawa, Satoshi; Matsumoto, Shinichi; Motohara, Tomofumi; Fukuda, Tetsuya; Yoshikawa, Takeshi
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.
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.
clinical diagnosis of portal hypertension is the determination of the different hemodynamic changes and, in particular, the determination of the rate...clinical data induced us to share some of our experience accumulated in studying hemodynamic changes in patients with portal hypertension » Beginning...in 1954 we directed our principal attention to determining the rate of portal blood flow in studying hemodynamic changes in patients with portal
Mercado, Miguel Angel; Orozco Zepeda, Héctor; Plata-Muñoz, Juan José
Treatment of portal hypertension has evolved widely during the last decades. Advances in physiopathology have allowed better application of therapeutic options and also have permitted to know the natural history of varices and variceal bleeding, predicting which patients have a higher risk of bleeding. It also permits probability of designing patient treatment. According to liver function and subadjacent liver disease, it is possible to offer different alternatives within the three possible scenarios (primary prophylaxis, acute bleeding episode, and secondary prophylaxis). For primary prophylaxis, pharmacotherapy offers the best choice. Endoscopic banding is also growing in these scenarios and probably will be accepted in the near future. For the acute bleeding episode, endoscopic therapy (sclerosis and/or bands) and/or pharmacologic therapy (octreotide, terlipresin) represent best choice, considering TIPS as a rescue option. Surgery is not used routinely in this scenario in most centers. For secondary prophylaxis, pharmaco- and endoscopic therapy are first-line treatments, while TIPS and surgery as second-line treatments. TIPS is mainly used in patients on a waiting list for liver transplantation. Surgery offers good results for low-risk patients, with good liver function and with portal blood-flow preserving procedures (selective shunts, extensive devascularizations). Liver transplantation is recommended for patients with poor liver function because together with portal hypertension, it treats subadjacent liver disease.
Balducci, Genoveffa; Sterpetti, Antonio V; Ventura, Marco
The aim of our study was to review the changing trends in the treatment of complications from portal hypertension. A short history of portal hypertension and of the treatment of its complications is reported, underlying the most important achievements and changes.
Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete e; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio
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
Manti, Sara; Marseglia, Lucia; D'Angelo, Gabriella; Filippelli, Martina; Cuppari, Caterina; Gitto, Eloisa; Romano, Claudio; Arrigo, Teresa; Salpietro, Carmelo
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
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; Diehl, Anna Mae; Trebicka, Jonel
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.
Anegawa, Go; Kawanaka, Hirofumi; Uehara, Hideo; Akahoshi, Tomohiko; Konishi, Kozo; Yoshida, Daisuke; Kinjo, Nao; Hashimoto, Naotaka; Tomikawa, Morimasa; Hashizume, Makoto; Maehara, Yoshihiko
This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension. Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child-Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation. The prevalence of PHG was significantly correlated with the severity of liver disease using the Child-Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child-Pugh score showed a significant improvement (6.8 +/- 1.4 to 6.2 +/- 1.2) at 3 months after laparoscopic splenectomy (P < 0.0001). PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.
Macaron, Carole; Pai, Rish K.; Alkhouri, Naim
Portal hypertension leading to gastric polyposis has rarely been reported. More common gastric manifestations of portal hypertension are portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE). We report a case of a patient in whom portal hypertension manifested as bleeding gastric polyps leading to transfusion-dependent iron deficiency anemia. PMID:26157923
Al Khalloufi, Kawtar; Laiyemo, Adeyinka O
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
K C, Sudhamshu; Matsutani, Shoichi; Maruyama, Hitoshi; Fukamachi, Tadahiro; Nomoto, Hiromasa; Akiike, Taro; Ebara, Masaaki; Saisho, Hiromitsu
The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.
Blendis, L M; Smith, P M; Lawrie, B W; Stephens, M R; Evans, W D
Hemodynamic studies were performed in 5 vinyl chloride monomer workers in whom splenomegaly or thrombocytopenia was detected during a screening program at major chemical plant. Three patients had portal hypertension and collateral venous circulations, with intrasplenic pressures between 20 and 29 mm Hg and normal wedged hepatic venous pressures, but the gradient between the wedged and free hepatic vein pressures was also increased. Splenic blood flows were increased in both hypertensive and normotensive patients. There was no correlation between the splenic blood flow and the portal pressure or the presence of portal fibrosis. The portal hypertension associated with vinyl chloride exposure is mainly presinusoidal in type, and may be attributed to an abnormality of the portal vein radicles, or hepatic sinusoids.
Cerpa Polar, Rusby; Castro Valdivia, Raúl; Valdez Herrera, Jesús
An analytic prospective study was done in cirrhotic patients with Portal hypertension to study a new pathology known as Portal Hypertensive Gastropathy. In 73.3 per cent of patients with cirrhosis, hospitalized inthe Gastroenterology Area, Portal Hypertensive Gastropathy was present. Males in the 4th decade of their life were predominant. Mild gastropathy with a mosaic or snake skin endoscopy pattern was the most frequent (60.6%), while in severe gastropathy, the most common pattern was cherry red spots. These lesions were often located in the stomach fundus and body. All the patients presented some vascular alteration and lymphoplasmocytic inflammatory infiltration. No relation was found between the severity of Portal Hypertension or Advanced Liver Disease and changes of the gastric mucosa.
Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David
Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field. PMID:28104976
Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David
Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field.
Leung, Jonathan Chung-Fai; Loong, Thomson Chi-Wang; Pang, James; Wei, Jeremy Lok; Wong, Vincent Wai-Sun
Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.
Vujanac, Andreja; Jakovljevic, Vladimir; Djordjevic, Dusica; Zivkovic, Vladimir; Stojkovic, Mirjana; Celikovic, Dragan; Andjelkovic, Nebojsa; Skevin, Aleksandra Jurisic; Djuric, Dragan
Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. 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 (O(2) (-)), hydrogen peroxide (H(2)O(2)), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO(2) (-)) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. Oxidative stress parameters changed significantly during the study. H(2)O(2) decreased at the end of study, probably via O(2) (-) mediated disassembling in Haber Weiss and Fenton reaction; O(2) (-) increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O(2) (-) and H(2)O(2) 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. This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension.
Orozco, H; Takahashi, T; Mercado, M A; Prado-Orozco, E; Ferral, H; Hernandez-Ortiz, J; Esquivel, E
We report three patients with colonic variceal bleeding secondary to portal hypertension, 0.5% of all cases with hemorrhagic portal hypertension studied by us in the last 16 years. One patient had idiopathic portal hypertension, and the others had extrahepatic portal vein thrombosis. Colonic varices were documented in all three cases by angiogram; large arteriovenous fistulas in the territory of the superior mesenteric artery and between the inferior mesenteric artery and hemorrhoidal veins were demonstrated in one patient. Two patients underwent colonoscopy; colonic varices were seen in only one. Two patients also had bled from esophagogastric varices. One patient underwent descending colon and sigmoid resection after failure to control bleeding with ligation of arterial supply; one patient underwent the Sugiura procedure, plus transanal ligation of hemorrhoids and rectal varices. At 3 months, 2 years, and 4 years of follow-up, the patients were in good general condition without any evidence of rebleeding.
Bomzon, A; Huang, Y T
Abnormal vascular responsiveness to ligands has been frequently observed in cirrhosis and portal hypertension, but its existence is not proven. The signaling pathways in vascular smooth muscle cells (VSMCs) have been studied only in animal models of cirrhosis and portal hypertension. Emerging evidence suggests that active relaxation, expressed as augmented content or activity of effectors within the cyclic AMP signaling pathway and suppressed content or activity of effectors in the inositol 1,4,5-trisphosphate/1,2-diacylglycerol signaling pathway, may be occurring in VSMCs of the splanchnic circulation in portal hypertension. The evidence supporting the existence of this phenomenon in the VSMCs of extrasplanchnic circulations in portal hypertension, as well as in the splanchnic circulation when chronic cellular damage is present, is very limited. The status of the other signaling pathways associated with contractile functions of the VSMCs, viz., cyclic GMP and tyrosine kinase-linked pathways, is unknown. The status of all the signaling pathways in non-contractile functions of VSMCs, such as growth and remodeling, has not been studied. As our overall understanding on the signaling pathways in VSMCs is only emerging, it is premature to implicate altered activity of the signaling pathways as the underlying basis of vascular hyporesponsiveness in cirrhosis and portal hypertension, and to extrapolate these limited observations to the human condition.
Yamagami, Takuji; Nakamura, Toshiyuki; Nishimura, Tsunehiko
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.
Sun, Xiao-Yu; Duan, Zhi-Jun; Liu, Zhen; Tang, Shun-Xiong; Li, Yang; He, Shou-Cheng; Wang, Qiu-Ming; Chang, Qing-Yong
The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.
Sun, Xiao-Yu; Duan, Zhi-Jun; Liu, Zhen; Tang, Shun-Xiong; Li, Yang; He, Shou-Cheng; Wang, Qiu-Ming; Chang, Qing-Yong
The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT. PMID:28105103
Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos
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.
Albillos, A; Rossi, I; Iborra, J; Lledó, J L; Calleja, J L; Barrios, C; García, P; Escartín, P
An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.
Mercado, M A; Takahashi, T; Rojas, G; Prado, E; Hernández, J; Tielve, M; Orozco, H
A prospective trial of a cohort of patients (N = 94) with portal hypertension and history of bleeding was selected for surgery based on strict clinical and laboratory criteria. All of them were treated with portal blood flow preserving procedures. The following selection criteria were used: good cardiopulmonary function without pulmonary hypertension and good liver function (Child-Pugh A). All patients were operated in an elective fashion and the operations performed were: selective shunts (N = 38) (distal splenorenal and splenocaval), low diameter mesocaval shunts (N = 13) and the esophagogastric devascularization with esophageal transection (Sugiura-Futagawa) (N = 43). Patients were selected for each operation according to their anatomical conditions. Sixty-one of the patients were cirrhotics. Operative mortality was 8% and rebleeding was observed in 5% of the cases. Postoperative encephalopathy was seen in seven patients (three selective shunts, two low diameter mesocaval shunts and two devascularizations). In 13 of 62 patients postoperatively evaluated by means of angiography, portal vein thrombosis was shown (seven selective shunts, two low diameter shunts and four devascularizations). Twenty-two patients with preoperative portal vein thrombosis (and treated with a Sugiura-Futagawa operation) were excluded from postoperative angiographic evaluation. Survival (Kaplan-Meier) was 85% at 60 months. Portal blood flow preserving procedures are the treatment of choice for patients with hemorrhagic portal hypertension and good liver function. The kind of operation is selected according to the individual anatomical status of the patient.
Wei, Wei; Pu, Yan-Song; Wang, Xin-Kai; Jiang, An; Zhou, Rui; Li, Yu; Zhang, Qiu-Juan; Wei, Ya-Juan; Chen, Bin; Li, Zong-Fang
AIM To investigate wall shear stress (WSS) magnitude and distribution in cirrhotic patients with portal hypertension using computational fluid dynamics. METHODS Idealized portal vein (PV) system models were reconstructed with different angles of the PV-splenic vein (SV) and superior mesenteric vein (SMV)-SV. Patient-specific models were created according to enhanced computed tomography images. WSS was simulated by using a finite-element analyzer, regarding the blood as a Newtonian fluid and the vessel as a rigid wall. Analysis was carried out to compare the WSS in the portal hypertension group with that in healthy controls. RESULTS For the idealized models, WSS in the portal hypertension group (0-10 dyn/cm2) was significantly lower than that in the healthy controls (10-20 dyn/cm2), and low WSS area (0-1 dyn/cm2) only occurred in the left wall of the PV in the portal hypertension group. Different angles of PV-SV and SMV-SV had different effects on the magnitude and distribution of WSS, and low WSS area often occurred in smaller PV-SV angle and larger SMV-SV angle. In the patient-specific models, WSS in the cirrhotic patients with portal hypertension (10.13 ± 1.34 dyn/cm2) was also significantly lower than that in the healthy controls (P < 0.05). Low WSS area often occurred in the junction area of SV and SMV into the PV, in the area of the division of PV into left and right PV, and in the outer wall of the curving SV in the control group. In the cirrhotic patients with portal hypertension, the low WSS area extended to wider levels and the magnitude of WSS reached lower levels, thereby being more prone to disturbed flow occurrence. CONCLUSION Cirrhotic patients with portal hypertension show dramatic hemodynamic changes with lower WSS and greater potential for disturbed flow, representing a possible causative factor of PV thrombosis. PMID:28566887
Zhang, S.Q.; Westfall, T.C.
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.
Orloff, M J; Orloff, M S; Orloff, S L; Haynes, K S
Portal hypertensive gastropathy is a vascular disorder of the gastric mucosa distinguished by ectasia of the mucosal capillaries and submucosal veins without inflammation. During 1988 to 1993, 12 patients with biopsy-proven cirrhosis (10 alcoholic, 2 posthepatitic) were evaluated and treated prospectively by portacaval shunt for active bleeding from severe portal hypertensive gastropathy. Eleven patients had been hospitalized for bleeding three to nine times previously, and one was bleeding uncontrollably for the first time. Requirement for blood transfusions ranged from 11 to 39 units cumulatively, of which 8 to 30 units were required specifically to replace blood lost from portal hypertensive gastropathy. Admission findings were ascites in 9 patients, jaundice in 8, severe muscle wasting in 10, hyperdynamic state in 9. Child's risk class was C in 7, B in 4, A in 1. Ten of the 12 patients had previously received repetitive endoscopic sclerotherapy for esophageal varices, which has been reported to precipitate portal hypertensive gastropathy. Eight patients had failed propranolol therapy for bleeding. Portacaval shunt was performed emergently in 11 patients and electively in 1, and permanently stopped bleeding in all by reducing the mean portal vein-inferior vena cava pressure gradient from 251 to 16 mm saline. There were no operative deaths, and two unrelated late deaths after 13 and 24 months. During 1 to 6.75 years of follow-up, all shunts remained patent by ultrasonography, the gastric mucosa reverted to normal on serial endoscopy, and there was no gastrointestinal bleeding. Recurrent portal-systemic encephalopathy developed in only 8% of patients. Quality of life was generally good.(ABSTRACT TRUNCATED AT 250 WORDS)
Van den Ingh, T S; Rothuizen, J; Meyer, H P
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.
Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Merton, Daniel A; Liu, Ji-Bin; Zhou, Jian-Hua; Wang, Hsin-Kai; Park, Suhyun; Dianis, Scott; Chalek, Carl L; Lin, Feng; Thomenius, Kai E; Brown, Daniel B; Forsberg, Flemming
The efficacy of using subharmonic emissions from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) to track portal vein pressures and pressure changes was investigated in 14 canines using either slow- or high-flow models of portal hypertension (PH). A modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI, USA) operating in subharmonic mode (f(transmit): 2.5 MHz, f(receive): 1.25 MHz) was used to collect radiofrequency data at 10-40% incident acoustic power levels with 2-4 transmit cycles (in triplicate) before and after inducing PH. A pressure catheter (Millar Instruments, Inc., Houston, TX, USA) provided reference portal vein pressures. At optimum insonification, subharmonic signal amplitude changes correlated with portal vein pressure changes; r ranged from -0.82 to -0.94 and from -0.70 to -0.73 for PH models considered separately or together, respectively. The subharmonic signal amplitudes correlated with absolute portal vein pressures (r: -0.71 to -0.79). Statistically significant differences between subharmonic amplitudes, before and after inducing PH, were noted (p ≤ 0.01). Portal vein pressures estimated using subharmonic aided pressure estimation did not reveal significant differences (p > 0.05) with respect to the pressures obtained using the Millar pressure catheter. Subharmonic-aided pressure estimation may be useful clinically for portal vein pressure monitoring.
Dave, Jaydev K.; Halldorsdottir, Valgerdur G.; Eisenbrey, John R.; Merton, Daniel A.; Liu, Ji-Bin; Zhou, Jian-Hua; Wang, Hsin-Kai; Park, Suhyun; Dianis, Scott; Chalek, Carl L.; Lin, Feng; Thomenius, Kai E.; Brown, Daniel B.; Forsberg, Flemming
The efficacy of using subharmonic emissions from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) to track portal vein pressures and pressure changes was investigated in 14 canines using either slow- or high-flow models of portal hypertension (PH). A modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI) operating in subharmonic mode (ftransmit:2.5MHz, freceive:1.25MHz) was used to collect RF data at 10-40% incident acoustic power levels with 2-4 transmit cycles (in triplicate), before and after inducing PH. A pressure catheter (Millar Instruments, Inc., Houston, TX) provided reference portal vein pressures. At optimum insonification, subharmonic signal amplitude changes correlated with portal vein pressure changes; r ranged from -0.82 to -0.94 and from -0.70 to -0.73 for PH models considered separately or together, respectively. The subharmonic signal amplitudes correlated with absolute portal vein pressures (r: -0.71 to -0.79). Statistically significant differences between subharmonic amplitudes, before and after inducing PH, were noted (p≤0.01). Portal vein pressures estimated using SHAPE did not reveal significant differences (p>0.05) with respect to the pressures obtained using the Millar pressure catheter. Subharmonic aided pressure estimation may be useful clinically for portal vein pressure monitoring. PMID:22920550
Suárez, Vanessa; Puerta, Andrés; Santos, Luisa Fernanda; Pérez, Juan Manuel; Varón, Adriana; Botero, Rafael Claudino
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.
Ge, Wei; Wang, Yi; Cao, Ya-Juan; Xie, Min; Ding, Yi-Tao; Zhang, Ming; Yu, De-Cai
Goal: To analyze the risk factors from radiological indices for hemorrhage in the patients with portal hypertension and weight risk factors. Method: We retrospectively analyzed all cases of portal hypertension with hepatitis B from June 2008 to June 2014 in Nanjing Drum Tower hospital. Patients with hepatocellular carcinoma, portal vein thrombosis, or portal hypertension with other causes, such as autoimmune hepatitis, pancreatitis, or hematological diseases were excluded. Results: Ninety-eight patients were recruited and divided into hemorrhage and non-hemorrhage groups. There were no statistical differences in clinical indexes such as age, prothrombin time, serum albumin, serum creatinine, serum sodium, hemameba, and blood platelet count. However, the differences were statistically significant in total bilirubin, hemoglobin, and liver function with the p values of 0.023, 0.000, and 0.039 respectively. For radiological indices, hemorrhage was correlated with diameter of inferior mesenteric vein (P=0.0528), posterior gastric vein (P=0.0283), and esophageal varices scores (P=0.0221). Logistic procedure was used to construct the model with stepwise selection and finally inferior mesenteric vein, posterior gastric vein, esophageal varices, and short gastric vein were enrolled into the model. These veins were scored according to the diameters and the rates of hemorrhage were increased with the score. We then validated the model with 26 patents from July 2014 to December 2014. The AUC value was 0.8849 in ROC curves for this radiological model. Conclusions: A risk model was constructed including inferior mesenteric vein, esophageal varices, posterior gastric vein, and short gastric vein. This radiological scoring model may be a valuable indicator for hemorrhage of portal hypertension. PMID:26617884
O'Sullivan, O. E.; Crosby, D.; Byrne, B.; Regan, C.
Biliary atresia is a rare idiopathic neonatal cholestatic disease characterized by the destruction of both the intra- and extrahepatic biliary ducts. As the disease is progressive all cases will develop portal fibrosis, cirrhosis, and portal hypertension with the sequelae of varices, jaundice, and eventually liver failure requiring a transplant. Survival rates have improved considerably with many females living well in to be childbearing age. Due to the complexity of the disease these pregnancies are considered, high risk. We report the antenatal, intrapartum, and postpartum managements of a pregnancy complicated by biliary atresia. Furthermore, we highlight the importance of a multidisciplinary team approach in optimizing obstetric care for this high risk group. PMID:24459595
Costaguta, Alejandro; Alvarez, Fernando
Portal hypertension causes serious and life-threatening complications. It is produced by increased resistance to blood flow through the portal axis, with a gradient to inferior vena cava higher than 5 mmHg. When this is 10 to 12 mmHg there is risk of bleeding from esophageal varices. In pediatric patients two different models exist: prehepatic (without liver disease), and intrahepatic (with liver disease), with different etiologies and prognosis. Doppler ultrasound, and liver function tests allow the distinction between them. Pediatricians should learn to recognize accurately the syndrome in order to approach the patients in a timely manner.
Xu, Wenxuan; Lu, Chunfeng; Zhang, Feng; Shao, Jiangjuan; Yao, Shunyu; Zheng, Shizhong
Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR). However, the effect of DHA on fibrosis-related portal hypertension still requires clarification. In this study, gain- and loss-of-function models of FXR in HSC were established to investigate the mechanisms underlying DHA protection against chronic CCl4 -caused hepatic fibrosis and portal hypertension. Immunofluorescence staining visually showed a decrease in FXR expression in CCl4 -administrated rat HSC but an increase in that in DHA-treated rat HSC. Serum diagnostics and morphological analyses consistently indicated that DHA exhibited hepatoprotective effects on CCl4 -induced liver injury. DHA also reduced CCl4 -caused inflammatory mediator expression and inflammatory cell infiltration. These improvements were further enhanced by INT-747 but weakened by Z-guggulsterone. Noteworthily, DHA, analogous to INT-747, significantly lowered portal vein pressure and suppressed fibrogenesis. Experiments on mice using FXR shRNA lentivirus consolidated the results above. Mechanistically, inhibition of HSC activation and contraction was found as a cellular basis for DHA to relieve portal hypertension. These findings demonstrated that DHA attenuated portal hypertension in fibrotic rodents possibly by targeting HSC contraction via a FXR activation-dependent mechanism. FXR could be a target molecule for reducing portal hypertension during hepatic fibrosis.
Mercado, M A; Orozco, H
Surgery for bleeding portal hypertension has evolved widely in the last decades. The surgical procedures that preserve portal blood flow are the first operative choice for well selected patients. Operative procedures that deprive the portal blood flow to the liver, are most likely to promote deterioration of liver function in the late postoperative period. The operation most frequently performed are the selective shunts (Warren) and the thoraco abdominal devascularization (Sugiura). The best results are obtained in patients with a good liver function that are operated in an elective fashion. Non-selective shunts have a restricted indication and low diameter porto systemic shunts are still under evaluation. The combination of drug therapy and/or sclerotherapy with surgery appears to improve survival. Liver transplants are indicated for those patients with associated liver failure. For patients with good liver function, surgery is the therapy of choice.
Nagi, B; Khandelwal, N; Kochhar, R; Gupta, B B; Mehta, S; Singh, K; Mehta, S K
Real time sonography followed by splenoportography was performed in 38 cases with non-cirrhotic portal hypertension. Eleven of these cases, in whom porto-systemic shunt surgery was done, were also evaluated by real time sonography post-operatively. The ultrasound findings correlated well in 37 cases (98%) with splenoportography. All the post-operative cases also revealed a patent portosystemic shunt on sonography. Ultrasonography, a valuable, non-invasive, initial investigation of portal hypertension, may thus be used as the only investigation to distinguish intra- from extra-hepatic obstruction and to evaluate patency of surgically created porto-systemic shunts. Invasive portography may be performed only if surgical treatment is anticipated.
Agarwal, Rakesh; Datta, Rajarshi; Saha, Manjari; Sarkar, Nirmalendu
Uhl's anomaly is a rare congenital heart disease characterized by partial or complete absence of the right ventricular myocardium and high early mortality rates. We describe a case of Uhl's anomaly in a 27-year-old young male patient presenting with portal hypertension and esophageal varices. In this article, we review the literature associated with this condition and highlight a rare presentation of a rare disease. This report adds to our current knowledge of this exceedingly rare disorder.
Garini, Giovanni; Delsante, Marco; Iannuzzella, Francesco
Portal hypertension is caused by an increased resistance to portal outflow and an increased portal blood inflow. Portal hypertension is associated with an abnormal distribution of the blood volume, which is increased in the splanchnic territory and reduced in the non-splanchnic compartments. The relative underfilling of the arterial circulation is responsible for the sodium and water retention, which is a consequence of the baroceptor-mediated activation of vasoconstrictor and antinatriuretic factors triggered to restore circulatory integrity.
de Franchis, Roberto; Dell'Era, Alessandra
Assessing the presence of clinically significant portal hypertension and esophageal varices is clinically important in cirrhosis. The reference standard techniques to assess the presence of portal hypertension and varices are the measurement of the hepatic vein pressure gradient and esophagogastroduodenoscopy, respectively. Some newer methods have shown a good performance, but none has been proven precise enough to replace hepatic vein pressure gradient measurement or esophagogastroduodenoscopy for the diagnosis of portal hypertension or the presence and grade of esophageal varices.
Chen, Wei; Luo, Meng; Sun, Yong-wei; Xu, Qing; Zhao, Gang; Hua, Rong; Liu, Wei; Jiang, Chun-hui; Shi, Chang-ying; Wu, Zhi-yong
To investigate the relationship between perioperative free portal pressure (FPP) after devascularization or spleno-renal shunt operation added devascularization and rebleeding or encephalopathy in patients with portal hypertension, and evaluate the relationship between dynamic changes of FPP and surgical approaches. The clinical data of 170 patients with portal hypertension receiving devascularization or devascularization with spleno-renal shunt operation (combination group) from January 2001 to December 2007 were retrospectively analyzed. All patients were divided into three groups: low pressure group [L group, after devascularization FPP
Snyder, Patrick; Ali, Rabia; Poles, Michael; Gross, Seth A
Portal hypertensive gastropathy (PHG) is a painless condition of gastric mucosal ectasia and impaired mucosal defense, commonly seen in patients with elevated portal pressures. While it is typically asymptomatic and incidentally discovered on upper endoscopy, acute and chronic bleeding may occur. There are no definitive recommendations for treatment of asymptomatic PHG. Non-selective β-blockers represent the mainstay of therapy for chronic bleeding, while somatostatin and vasopressin and their derivatives may be used in conjunction with supportive measures for acute bleeding. Salvage therapy with transjugular intrahepatic portosystemic shunt or rarely surgical shunt is appropriate when medical management fails. The role of endoscopic therapy for PHG is controversial. Liver transplantation should be considered as a final resort in cases of refractory bleeding due to PHG.
Procopeţ, Bogdan; Tantau, Marcel; Bureau, Christophe
Portal hypertension is a major consequence of any chronic liver disease and it represents the main mechanism of complication occurrence. Therefore, the assessment of portal hypertension presence is one of the most important steps in the management of any chronic liver diseases. The most accurate tool for portal pressure assessment is hepatic venous pressure gradient (HVPG) measurement, which has diagnostic and prognostic relevance. In this paper we review the methodology of HVPG measuring, together with the clinical relevance of this technique. Portal hypertension is defined as a HVPG higher than 5 mmHg, but clinically significant portal hypertension that predisposes to clinical decompensation is defined as HVPG higher than 10 mmHg. HVPG is useful for portal hypertension treatment monitoring. A decrease in HVPG greater than 20% or under the threshold of 12 mmHg is considered to be protective against portal hypertension-related events. Even if HVPG measurement is a safe procedure, it is still considered an invasive technique and not widely available. Therefore, non-invasive markers of portal hypertension were searched for. Until now only liver stiffness measurement by transient elastography has proved to be sufficiently accurate but there is still heterogeneity among the cut-off values for portal hypertension diagnosis.
Ricci, Lidia; Pelosi, Marcello; Ricci, Serafino
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
Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy. PMID:22453061
Sevriugov, B L; Ulŕikh, E V; Korolev, M P; Kupatadze, D D; Ivanov, A P; Nabokov, V V
In the period from 1985 to 1992 sixty-three patients aged from 7 months to 15 years were treated for the portal hypertension syndrome, 60 had the extrahepatie form. Forty-five various operations for portosystemic shunting were carried out: formation of proximal splenorenal anastomosis in 31, distal splenorenal anastomosis in 4, mesentericocaval anastomosis in 6, gastrocaval anastomisis in 2, and an atypical vascular shunt in 2 cases. Nonshunting operations were performed on 8 patients. Since 1986 39 sessions of endoscopic sclerotherapy were conducted, 16 of them were carried out in cases with esophagogastric bleeding.
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
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.
Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam
Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.
Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam
Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management. PMID:28348478
Pierce, James R; Hunter, Catherine J; Naik-Mathuria, Bindi; Stanley, Philip; Ford, Henri R; Genyk, Yuri; Shaul, Donald B; Panossian, Andre; Anselmo, Dean M
We present a case of an adolescent with lower gastrointestinal bleeding caused by a colorectal venous malformation (VM) with concomitant portal hypertension. After an episode of massive gastrointestinal bleeding, we performed an extended right hemicolectomy and resection of the VM and selective portosystemic shunt. Here, we present the case and review the literature regarding portal hypertension and gastrointestinal vascular malformations. Additionally, we discuss the physiologic and hemodynamic effects of gastrointestinal vascular malformations on the portal system.
Gordon, D.T.; Leinart, A.S.; Cousins, R.J.
The distribution of newly absorbed copper among serum proteins obtained from the portal circulation of rats was examined by conventional and high-performance gel filtration chromatography, affinity chromatography, and Western blotting. Within 10-30 min after being administered by gavage or directly into the intestine, /sup 67/Cu and /sup 64/Cu, respectively, were recovered in the albumin fraction. By 8 h after administration of the radionuclides, virtually all of the radioactivity was found with ceruloplasmin. Affigel blue fractionation and subsequent Superose-6 chromatography further demonstrated that all of the copper in the albumin-containing fractions was in fact bound to this protein rather than high molecular weight moieties. Vascular perfusion of the isolated rat intestine, where /sup 64/Cu was infused into the lumen, showed that newly absorbed /sup 64/Cu in the vascular perfusate collected from the cannulated portal vein was associated with albumin. Uptake of radioactivity by isolated rat liver parenchymal cells from medium containing rat serum with /sup 67/Cu bound to albumin was demonstrated. In vitro binding of /sup 64/Cu to serum proteins that were transferred to nitrocellulose by Western blotting techniques showed that albumin is essentially the only protein that binds appreciable amounts of copper. The data suggest that albumin is the plasma protein that is responsible for the initial transport of copper after absorption.
Stock, Heather; Kadry, Zakiyah; Smith, Jill P
Bleeding esophageal varices are a common complication of portal hypertension in patients with underlying liver disease. Often patients with hepatic cirrhosis have hypersplenism with thrombocytopenia and leukopenia. Felty's syndrome is a disorder where patients with rheumatoid arthritis develop splenomegaly, neutropenia, and on rare occasions, portal hypertension without underlying cirrhosis. We present a case of a patient with portal hypertension secondary to Felty's syndrome and discuss the importance of recognizing this condition since the treatment of choice is surgical management with splenectomy. A review of the literature and underlying liver histologic features are discussed. Medical and surgical management of patients with Felty's syndrome is different from those with portal hypertension due to cirrhosis. Splenectomy is the treatment of choice for complications of portal hypertension in patients with Felty's Syndrome.
Qian, J; Feng, G; Liang, H
To explore a new way of utilizing intervential treatment to effectively decrease the portal hypertension, the animal models of liver cirrhosis accompanying portal hypertension were set up by intraportal vein injection of suspensions of Bletilla striata to 10 rabbits by means of prospective investigational method. The catheter filled with heparin solution was remained in theportal vein for infusion of drugs. Three weeks later, DDPH solution was injected into the portal vein via the catheter to determine its effect of decreasing portal vein pressure and its influence of peripheral blood pressure and heart rate. At the same time, other 10 rabbits with liver cirrhosis associated with portal hypertension were subjected to the injection of DDPH solution via the ear vein served as control group. The results showed that administration of DDPH by portal vein could rapidly, safely and effectively decrease the portal hypertenive pressure without side effects and partially reverse liver cirrhosis, as compared with injection of DDPH via peripheral veins. It was concluded that DDPH exerted its alpha 1-adrenoceptor blocking and calcium antagonistic effects, thereby significantly reduce the portal hypertension. Injection of DDPH via portal vein is a completely new and relaible method for the treatment of liver cirrhosis with portal hypertension.
Bernard, O; Alvarez, F; Alagille, D
The retrospective study of 115 children in whom a successful portosystemic shunt was carried out for portal hypertension, provides the following conclusions: 1) Patency of the shunt must be checked by esophageal endoscopy, six months postoperatively. A patent shunt can be expected when the size of the spleen and/or thrombocytopenia improve in the early post-operative period. Early ultrasound examination is also very useful in that respect. 2) None of the children with extrahepatic portal vein obstruction or congenital hepatic fibrosis presented with clinical signs of portal systemic encephalopathy (PSE). 3) Eight of 30 children with cirrhosis presented with one or more clinical episodes of PSE. Some were transient allowing for a normal diet to be resumed later on. 4) It is thus advisable to give children with cirrhosis a low protein diet in the months after surgery. Protein content of the diet can usually be increased progressively over a period of one to two years. 5) Whenever splenectomy is necessary, it is mandatory to prevent pneumococcal infections with the pneumococcal vaccine and daily treatment with oral penicillin.
Dasarathy, Srinivasan; Mullen, Kevin D; Conjeevaram, Hari S; Kaminsky-Russ, Kristine; Wills, Laurie A; McCullough, Arthur J
The portacaval anastomosis (PCA) rat model and human cirrhosis have many metabolic and nutritional abnormalities in common, such as growth retardation, hepatic and gonadal atrophy, and hyperammonemia. The severity of these abnormalities is variable and may be related to a number of factors, including portal pressure, portosystemic shunting, dietary intake, and how efficiently food is used. Therefore, this rat model was used to study these variables with the intent of gaining insights for improving the management of portal hypertension and malnutrition in human cirrhosis. A nonsuture end-to-side PCA (N = 100) or sham surgery (N = 71) was performed in 100 male rats. Four weeks after surgery, body and organ weights, food intake, serum ammonia, and serum amino acids were measured at death. In a subgroup of rats, (sham 7; PCA 34) portal venous pressure, degree of portosystemic shunting, and organ and body weights were obtained at death. Growth, liver weight, and testes weight were decreased, ammonia levels were higher, and the ratios of branched chain to aromatic amino acid (BCAA/AAA) were lower in the PCA group compared to the sham animals (P < 0.05). Since spleen weights correlated with portal pressure (P = 0.01), the PCA animals were then divided into those with preserved and those with low portal pressures based on spleen weight. The PCA group with preserved portal pressure had better growth, larger livers and testes, lower serum ammonia, and higher BCAA/AAA levels than the PCA group with low portal pressure; improvements associated with normal amounts of food intake and better food efficiency than the low pressure animals (P < 0.05 or better). Sham animals had no portosystemic shunting, while 100% shunting occurred in both PCA groups regardless of the portal pressure. In conclusion, preservation of portal pressure after portacaval anastomosis provides metabolic and nutritional benefits, which are independent of portosystemic shunting and associated with normal
Cao, Y J; Pan, Y M; Bao, S H; Lu, C L; Xu, B Y; Xie, M
Objective: To explore the prognostic factors of portal hypertension treated with devascularization. Methods: A total of 397 patients with portal hypertension underwent devascularization in Nanjing Drum Tower Hospital from February 1993 to April 2014, among which there were 242 male and 155 female patients with median age of 48 years. The perioperative data were retrospectively collected. Logistic regression was used to find the risk factors which affect the operative complications. Follow-up evaluation was in progress regularly. Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to find out factors which affect the long-term results. Results: All together 397 patients underwent devascularization, in whom 8 patients died perioperative, 389 patients discharged successfully. Logistic regression showed that age (≥48 years) (χ(2)=4.559, OR=2.048, P=0.033), red color sign before surgery (χ(2)=4.959, OR=2.129, P=0.026) and without portosystemic collateral vessels reserved (χ(2)=13.348, OR=5.122, P=0.000) were risk factors of perioperative complications. The follow-up time was (5.7±4.6) years. Totally 27 patients were lost from follow-up, 103 patients died for the disease during follow-up. The survival rate at 1-, 3-, 5-, 10-, 15- and 20-years was 93.6%, 86.9%, 80.1%, 59.3%, 54.1% and 38.5% respectively.Univariate analysis showed that gender (male), age (≥48 years), hemorrhage before surgery (≥500 ml per time), hepatitis virus and without portosystemic collateral vessels reserved were risk factors of the long-term survival (P<0.05). Cox regression analysis showed that age (≥48 years) (χ(2)=9.850, RR=1.904, P=0.002), hemorrhage before surgery (≥500 ml per time) (χ(2)=34.402, RR=3.273, P=0.000), hepatitis virus (χ(2)=7.573, RR=2.525, P=0.006) and without portosystemic collateral vessels reserved (χ(2)=5.905, RR=1.889, P=0.015) were independent risk factors that affect the long-term survival. Conclusion: Devascularization with
Garbuzenko, Dmitry Victorovich
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
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
Kashiwagi, T.; Azuma, M.; Ikawa, T.; Takehara, T.; Matsuda, H.; Yoshioka, H.; Mitsutani, N.; Koizumi, T.; Kimura, K.
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.
Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana
Pulmonary arterial hypertension (PAH) is a rare disease that could be inherited with an autosomal dominant pattern. Mutations in BMPR2 gene are described in over 70% of cases, although other genes are involved in lesser extend in PAH. Hereditary hemorrhagic telangiectasia (HHT) is another rare autosomal dominant disease. PAH is a rare complication of HHT that occurs in less than 1% of cases. Liver cirrhosis with portal hypertension is also associated with the presence of PAHs in 1-2% of cases. We present here a patient with HHT who developed PAH shortly after showing portal hypertension. Some genes (BMPR2, ACVRL1, ENG) seem to play an important role in PAH pathogenesis. We analyzed these genes, detecting mutations in BMPR2 gene (c.1021G>A (V341L), c.327G>A (p.Q109Q)), ACVRL1 (c.313+20C>A, c.1502+7A>G) and ENG (c.498G>A (Q166Q)). The patient also had 3 polymorphisms in the TRPC6 gene (c.1-361A>T, c.1-254C>G, c.1-218C>T). The study of these genes will help us to identify and track individuals susceptible for developing PAH associated with other diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Kichikawa, Kimihiko; Saxon, Richard R.; Nishimine, Kiyoshi; Nishida, Norifumi; Uchida, Barry T.
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.
Alghamdi, Sharifa A; Saadah, Omar I; Almatury, Nesreen; Al-Maghrabi, Jaudah
Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy.
Alghamdi, Sharifa A.; Saadah, Omar I.; Almatury, Nesreen; Al-Maghrabi, Jaudah
Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy. PMID:22626802
Patrono, Damiano; Benvenga, Rosa; Moro, Francesco; Rossato, Denis; Romagnoli, Renato; Salizzoni, Mauro
INTRODUCTION Left-sided portal hypertension is a rare clinical condition most often associated with a pancreatic disease. In case of hemorrhage from gastric fundus varices, splenectomy is indicated. Commonly, the operation is carried out by laparotomy, as portal hypertension is considered a relative contraindication to laparoscopic splenectomy (LS). Although some studies have reported the feasibility of the laparoscopic approach in the setting of cirrhosis-related portal hypertension, experience concerning LS in left-sided portal hypertension is lacking. PRESENTATION OF CASE A 39-year-old man was admitted to the Emergency Department for haemorrhagic shock due to acute hemorrhage from gastric fundus varices. Diagnostic work up revealed a chronic pancreatitis-related splenic vein thrombosis causing left-sided portal hypertension with gastric fundus varices and splenic cavernoma. Following splenic artery embolization (SAE), the case was successfully managed by LS. DISCUSSION The advantages of laparoscopic over open splenectomy include lower complication rate, quicker recovery and shorter hospital stay. Splenic artery embolization prior to LS has been used to reduce intraoperative blood losses and conversion rate, especially in complex cases of splenomegaly or cirrhosis-related portal hypertension. We report a case of complicated left-sided portal hypertension managed by LS following SAE. In spite of the presence of large varices at the splenic hilum, the operation was performed by laparoscopy without any major intraoperative complication, thanks to the reduced venous pressure achieved by SAE. CONCLUSION Splenic artery embolization may be a valuable adjunct in case of left-sided portal hypertension requiring splenectomy, allowing a safe dissection of the splenic vessels even by laparoscopy. PMID:25194596
McCarty, Thomas R.; Hung, Adelina; Mohanty, Arpan
Systemic mastocytosis is a myeloproliferative disorder characterized by extracutaneous involvement of at least one organ. Although rare, infiltration of inflammatory mast cells within the portal vein may lead to obstruction of the sinusoids resulting in non-cirrhotic portal hypertension. We present a patient with known history of systemic mastocytosis with bone marrow involvement presenting with new-onset esophageal variceal bleeding. Although systemic mastocytosis is uncommon, the subsequent development of hepatic involvement and non-cirrhotic portal hypertension are discussed. Further highlighted is a lack of organization guidelines and the potential for gastrointestinal and hepatic screening of mastocytosis patients with known extracutaneous involvement. PMID:28286795
El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal
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
El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal
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
Vorobioff, Julio D.; Groszmann, Roberto J
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
Thiele, Maja; Kjaergaard, Maria; Thielsen, Peter; Krag, Aleksander
The risk and speed of progression from fibrosis to compensated and decompensated cirrhosis define the prognosis in liver diseases. Therefore, early detection and preventive strategies affect outcomes. Patients with liver disease have traditionally been diagnosed at an advanced stage of disease, in part due to lack of non-invasive markers. Ultrasound elastography to measure liver stiffness can potentially change this paradigm. The purpose of this review was therefore to summarize advances in the field of ultrasound elastography with focus on diagnosis of liver fibrosis, cirrhosis and clinically significant portal hypertension, techniques and limitations. Four types of ultrasound elastography exist, but there is scarce evidence comparing the different techniques. The majority of experience concern transient elastography for diagnosing fibrosis and cirrhosis in patients with chronic viral hepatitis C. That said, the role of elastography in other aetiologies such as alcoholic- and non-alcoholic liver fibrosis still needs clarification. Although elastography can be used to diagnose liver fibrosis and cirrhosis, its true potential lies in the possibility of multiple, repeated measurements that allow for treatment surveillance, continuous risk stratification and monitoring of complications. As such, elastography may be a powerful tool for personalized medicine. While elastography is an exciting technique, the nature of ultrasound imaging limits its applicability, due to the risk of failures and unreliable results. Key factors that limit the applicability of liver stiffness measurements are as follows: liver vein congestion, cholestasis, a recent meal, inflammation, obesity, observer experience and ascites. The coming years will show whether elastography will be widely adapted in general care.
Lu, Ling; Zhang, Feng; Li, Xiang-Cheng; Li, Guo-Qiang; Zhang, Chuan-Yong; Wang, Xue-Hao
Portopulmonary hypertension (PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension, with or without advanced hepatic disease. Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state. Similar signs of advanced liver disease can be observed in severe PPH, with ascites and lower extremity edema. Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation (LT). We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis. Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years, it was necessary to send him to the intensive care unit after operation. Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality. PMID:19084945
Reddy, Asha; Sanniyasi, Saravanan; George, Dilip Joseph; Narayanan, Cunnigaiper Dhanasekaran
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
Garbuzenko, Dmitry Victorovich; Arefyev, Nikolay Olegovich; Belov, Dmitry Vladimirovich
In recent years, defined progress has been made in understanding the mechanisms of hemodynamic disturbances occurring in liver cirrhosis, which are based on portal hypertension. In addition to pathophysiological disorders related to endothelial dysfunction, it was revealed: There is the restructuring of the vasculature, which includes vascular remodeling and angiogenesis. In spite of the fact that these changes are the compensatory-adaptive response to the deteriorating conditions of blood circulation, taken together, they contribute to the development and progression of portal hypertension causing severe complications such as bleeding from esophageal varices. Disruption of systemic and organ hemodynamics and the formation of portosystemic collaterals in portal hypertension commence with neovascularization and splanchnic vasodilation due to the hypoxia of the small intestine mucosa. In this regard, the goal of comprehensive treatment may be to influence on the chemokines, proinflammatory cytokines, and angiogenic factors (vascular endothelial growth factor, placental growth factor, platelet-derived growth factor and others) that lead to the development of these disorders. This review is to describe the mechanisms of restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension. Development of pathogenetic methods, which allow correcting portal hypertension, will improve the efficiency of conservative therapy aimed at prevention and treatment of its inherent complications. PMID:28083082
Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas
AIM: To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. METHODS: Wild type, eNOS-/- and iNOS-/- mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. RESULTS: In wild type and iNOS-/- mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS-/- mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS-/- mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS-/- and iNOS-/- sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in
Portmann, B; Stewart, S; Higenbottam, T W; Clayton, P T; Lloyd, J K; Williams, R
A case of multiple focal nodular hyperplasia (FNH) of the liver associated with noncirrhotic portal hypertension and later complicated by pulmonary arterial hypertension leading to death from right heart failure is reported. In retrospect, the portal hypertension diagnosed in early life was most likely due to a congenital hypoplasia of portal vein branches and multiple FNH, a hyperplastic response of the liver parenchyma in association with anomalies of hepatic arterial branches as found within the lesions. This case may represent a form of multiple FNH syndrome restricted to the liver, because neither extrahepatic vascular malformation nor brain tumor was identified at autopsy. The FNH lesions had considerably expanded over the years, and the severe sinusoidal congestion due to chronic right-sided heart failure with subsequent prolonged parenchymal exposure to blood-borne hepatotrophic factors is a likely explanation for both the massive enlargement of FNH lesions and the nodular regenerative hyperplasia observed in the intervening parenchyma.
Gentilucci, Umberto Vespasiani; Gallo, Paolo; Perrone, Giuseppe; Vescovo, Riccardo Del; Galati, Giovanni; Spataro, Sandro; Mazzarelli, Chiara; Pellicelli, Adriano; Afeltra, Antonella; Picardi, Antonio
Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory disturbances. More flexibility in classification should derive from this etiopathogenic background. PMID:21633664
Acute esophageal variceal hemorrhage is a terrible complication of portal hypertension and. rebleeding is very common in survivors of acute variceal bleeding. Traditional medical management options include the use of vasoconstrictor, balloon tamponade, and endoscopic therapy. Though endoscopic therapy has achieved successful hemostasis in the majority of acute variceal bleeding episodes, the outcome is usually dismal when such therapy fails. Transjugular intrahepatic portosystemic stent shunt (TIPS) was invented to decompress portal hypertension, but is now widely used in Western countries to treat patients with refractory variceal hemorrhage or refractory ascites. By contrast, TIPS has not been commonly used in Asia. In this article, I have reviewed the role of TIPS in the management of portal hypertensive bleeding, which will hopefully be useful for clinicians facing variceal bleeding that is not amenable to endoscopic therapies. Copyright © 2014. Published by Elsevier B.V.
Liu, Kai; Fan, Xin-Xin; Wang, Xu-Lin; He, Chang-Sheng; Wu, Xing-Jiang
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
Liu, Kai; Fan, Xin-Xin; Wang, Xu-Lin; He, Chang-Sheng; Wu, Xing-Jiang
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.
Prasad, G. Raghavendra; Billa, Srikar; Bhandari, Pavaneel; Hussain, Aijaz
Extrahepatic portal hypertension is not an uncommon disease in childhood, but isolated inferior mesenteric portal varices and lower gastrointestinal (GI) bleed have not been reported till date. A 4-year-old girl presented with lower GI bleed. Surgical exploration revealed extrahepatic portal vein obstruction with giant inferior mesenteric vein and colonic varices. Inferior mesenteric vein was joining the superior mesenteric vein. The child was treated successfully with inferior mesenteric – inferior vena caval anastomosis. The child was relieved of GI bleed during the follow-up. PMID:23798814
Zhang, Jin-Shan; Cheng, Wei; Li, Long
Abstract Background: The distal splenorenal shunt is an effective procedure for the treatment of portal hypertension in children. However, there has been no report about laparoscopic distal splenorenal shunt in the treatment of portal hypertension in children. Methods: From December 2015 to August 2016, 4 children with upper gastrointestinal bleeding underwent laparoscopic distal splenoadrenal shunt. Portal hypertension and splenomegaly were demonstrated on the preoperative computed tomography (CT) and sonography. The distal splenic vein was mobilized and anastomosed to the left adrenal vein laparoscopically. All patients were followed-up postoperatively. Results: The laparoscopic distal splenoadrenal shunt was successfully performed in all patients. The liver fibrosis was diagnosed by postoperative liver pathology. The operative time ranged from 180 to 360 minutes. The blood loss was minimal. The length of hospital stay was 6 to 13 days. The duration of following-up was 1 to 9 months (median: 3 months). The portal pressure and splenic size were decreased postoperatively. The complete blood count normalized and the biochemistry tests were within normal range after surgery. Postoperative ultrasound and CT confirmed shunt patency and satisfactory flow in the splenoadrenal shunt in all patients. No patient developed recurrence of variceal bleeding. Conclusions: The laparoscopic splenoadrenal shunt is a feasible treatment of portal hypertension in children. PMID:28099341
Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei
To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and
Eisinger, Kristina; Krautbauer, Sabrina; Wiest, Reiner; Karrasch, Thomas; Hader, Yvonne; Scherer, Marcus N; Farkas, Stefan; Aslanidis, Charalampos; Buechler, Christa
Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.
Gjeorgjievski, Mihajlo; Cappell, Mitchell S
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
Sun, Yong-Wei; Chen, Wei; Luo, Meng; Hua, Rong; Liu, Wei; Huo, Yan-Miao; Wu, Zhi-Yong; Cao, Hui
Various surgical procedures can be used to treat liver cirrhosis and portal hypertension. How to select the most appropriate procedure for patients with portal hypertension has become a difficult problem. This study aimed to analyze the relationship between the value of intraoperative free portal pressure (FPP) and postoperative complications, and to explore the significance of intraoperative FPP measurement with respect to surgical procedure selection. The clinical data of 187 patients with portal hypertension who received pericardial devascularization and proximal splenorenal shunt combined with devascularization (combined operation) at the Department of General Surgery in our hospital from January 2001 to September 2008 were retrospectively analyzed. Among the patients who received pericardial devascularization, those with a postoperative FPP >or=22 mmHg were included in a high-pressure group (n=68), and those with FPP <22 mmHg were in a low-pressure group (n=49). Seventy patients who received the combined operation comprised a combined group. The intraoperative FPP measurement changes at different times, and the incidence of postoperative complications in the three groups of patients were compared. The postoperative FPP value in the high-pressure group was 27.5+/-2.3 mmHg, which was significantly higher than that of the low-pressure (20.9+/-1.8 mmHg) or combined groups (21.7+/-2.5 mmHg). The rebleeding rate in the high-pressure group was significantly higher than that in the low-pressure and combined groups. The incidence rates of postoperative hepatic encephalopathy and liver failure were not statistically different among the three groups. The mortality due to rebleeding in the low-pressure and combined groups (0.84%) was significantly lower than that of the high-pressure group. The study demonstrates that FPP is a critical measurement for surgical procedure selection in patients with portal hypertension. A FPP value >or=22 mmHg after splenectomy and
Segarra, Gloria; Cortina, Belén; Mauricio, María Dolores; Novella, Susana; Lluch, Paloma; Navarrete-Navarro, Javier; Noguera, Inmaculada; Medina, Pascual
AIM To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. METHODS Rat renal arteries from Sham (n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10-9-3 × 10-6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD2 values to ADMA were similar in the Sham and PPVL groups (4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group (4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of pD2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA (3 × 10-4 mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher (P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The mRNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased (P < 0.05) in PPVL and further enhanced (P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney. PMID:28082806
Herath, Chandana B; Grace, Josephine A; Angus, Peter W
Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis. Drug therapy to reduce portal pressure involves targeting two vascular beds. The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin II, endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells. The second approach is to reduce mesenteric and portal blood flow. Non-selective β-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis. However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients. Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding. This review briefly outlines current therapeutic approaches to the management of portal hypertension, and the evidence supporting the role of the renin angiotensin system (RAS) and the use of RAS blockers in this condition. It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered “alternate axis” of the RAS. PMID:23596549
Mörl, M; Schwalbach, G; Wannagat, L; Bavastro, P
Liver damage influenced by alcohol is already associated with the development of a portal hypertension at an early stage. With the aid of laparoscopic transhepatic manometry we determined the pressure levels in the branches of the portal and hepatic veins in 15 patients (16 examinations) comprising 14 men and 1 women, with alcoholic toxic liver damage. It was shown that already with alcoholic parenchymal damage associated with portal and centrolobular fibrosis, a portal hypertension is initiated, the greatest manifestation of which is found in the group with histological changes taking the form of a remodelling (distorsion of architecture) or cirrhosis. The level of alcohol consumption has no direct influence on the level of pressure in the vascular systems investigated. Ther is, however, a correlation between the level of alcohol consumption, extent of fibrosis and portal hypertension. For the clinico-chemical parameters investigated (Gamma-glob., GOT, GPT, GLDH, gamma-GT, alkaline phosphatase, bilirubin) no significant differences were found dependent on the level of alcohol consumption or the degree of fibrosis.
Obladen, M; Ernst, D; Feist, D; Wille, L
10 children presented pre-hepatic portal vein obstruction during their first 6 years of life. 8 of them had massive esophageal varices, 1 died from acute esophageal hemorrhage. The perinatal history of these childre was studied: All of them had an abnormal birth history and all had been hospitalized during their neonatal period. In 5 of them an umbilical infection had been diagnosed, one had an injection of THAM and one other an exchange transfusion through an umbilical vein catheter. Pre-hepatic portal vein occlusion in children is presumed to be mainly an acquired disease resulting from neonatal umbilical disorders.
Kalambokis, Georgios; Christou, Leonidas; Stefanou, Dimitrios; Arkoumani, Evdokia; Tsianos, Epameinondas V
A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed. PMID:17963311
Kalambokis, Georgios; Christou, Leonidas; Stefanou, Dimitrios; Arkoumani, Evdokia; Tsianos, Epameinondas V
A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.
Hulkower, Benjamin M.; Butty, Sabah
Arterioportal fistulas (APFs) are a group of vascular disorders, in which systemic arteries communicate with the portal circulation, presenting as a congenital syndrome or more commonly acquired from iatrogenic instrumentation or abdominal trauma. We report the case of a 58-year-old man who developed ascites without underlying risk factors for portal hypertension, which was attributed to an APF found on imaging, manifesting 43 years after sustaining a liver laceration. After angiographic embolization of the APF, the patient’s ascites resolved completely. The prolonged latent period between the patient’s abdominal trauma and eventual presentation with ascites highlights the need to consider vascular malformations in the differential diagnosis of unexplained noncirrhotic portal hypertension. PMID:27807573
Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr
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
Costaguta, Alejandro; Alvarez, Fernando
Portal hypertension in children represents a particular diagnostic and management challenge for several reasons: (1) treatment outcomes should be evaluated in relationship with a long-life expectancy, (2) pediatric patients with portal hypertension constitute an heterogeneous population, both in terms of individual characteristics and diversity of liver diseases; making comparison between treatment outcomes very difficult, (3) application of techniques and procedures developed in adult patients (v.gr. TIPS) face size limitations in small children, and (4) absence of data from well-controlled trials in children forces pediatric specialists to adapt results obtained from adult cohorts suffering from diseases such as HCV and alcoholic cirrhosis. Despite those limitations, substantial progress in the treatment of children with portal hypertension has been achieved in recent years, with better outcomes and survival. Two main factors influence our therapeutic decision: age of the patient and etiology of the liver disease. Therefore, diagnosis and treatment of complications of portal hypertension in children need to be described taking such factors into consideration. This paper summarizes current knowledge and expert opinion. PMID:23097711
Costaguta, Alejandro; Alvarez, Fernando
PORTAL HYPERTENSION IN CHILDREN REPRESENTS A PARTICULAR DIAGNOSTIC AND MANAGEMENT CHALLENGE FOR SEVERAL REASONS: (1) treatment outcomes should be evaluated in relationship with a long-life expectancy, (2) pediatric patients with portal hypertension constitute an heterogeneous population, both in terms of individual characteristics and diversity of liver diseases; making comparison between treatment outcomes very difficult, (3) application of techniques and procedures developed in adult patients (v.gr. TIPS) face size limitations in small children, and (4) absence of data from well-controlled trials in children forces pediatric specialists to adapt results obtained from adult cohorts suffering from diseases such as HCV and alcoholic cirrhosis. Despite those limitations, substantial progress in the treatment of children with portal hypertension has been achieved in recent years, with better outcomes and survival. Two main factors influence our therapeutic decision: age of the patient and etiology of the liver disease. Therefore, diagnosis and treatment of complications of portal hypertension in children need to be described taking such factors into consideration. This paper summarizes current knowledge and expert opinion.
Mejías Manzano, María de Los Ángeles; Giráldez Gallego, Álvaro; Sánchez Torrijos, Yolanda María
Supportive transfusion represents a basic tool in the management of gastrointestinal (GI) bleeding. However, the use of hemoderivatives is not exempt from risks such as development of hemolysis. We report a case of post-transfusion hyperhemolysis syndrome in a female patient with prehepatic portal hypertension.
Kainberger, F M; Vergesslich, K A; Eilenberger, M; Poeltner, S; Ponhold, W
A 11-year-old white girl presented with a diagnosis of thrombosis of the portal vein after newborn septicemia. Duplex sonography revealed significant narrowing of the portal vein and its right and left branches. A Doppler signal could only be obtained in certain short segments of the portal vein and indicated hepatopetal flow. Color-coded Doppler sonography showed extensive varicose veins in the gallbladder with a bigger draining vessel running to the porta hepatis. Documentation of varices like those in the gallbladder wall confirms the diagnosis of portal hypertension and may increase the sensitivity of Doppler sonography. Color mapping has the potential to detect unexpected flow and to analyze blood flow to better advantage.
Jagroop, Sophia; Parthvi, Rukma
Both polycystic liver disease (PLD) and sarcoidosis can involve liver. Most of the time, liver disease in both conditions is asymptomatic, but they can rarely cause portal hypertension. Our aim is to report a case of a 51-year-old female with a history of adult dominant polycystic kidney disease (ADPKD) and sarcoidosis who presented with multiple episodes of hematemesis. An endoscopy showed grade 3 esophageal varices. A computed tomography (CT) scan of the abdomen showed ascites with polycystic liver, nodular contour, and calcified granuloma. PLD can cause portal hypertension due to fibrosis or large cysts compressing on the portal vein. On the other hand, sarcoidosis causes portal hypertension by formation of arteriovenous(AV) shunts or fibrosis in areas of granulomas. Both conditions are diagnosed on imaging. There is no approved medical treatment for PLD; the only curative treatment is liver transplantation. Asymptomatic hepatic sarcoidosis does not need any treatment. The recommended treatment is corticosteroids for both isolated and systemic sarcoidosis. ADPKD and sarcoidosis can involve multiple organs. The presence of both conditions can accelerate the disease process and could be a therapeutic challenge. Early abdominal imaging during the course of both diseases can improve the outcome by decreasing the diagnostic window. PMID:28280650
Martelli, H; Carlier, J C; Ducot, B; Alagille, D; Valayer, J
From 1959 until 1981, 157 children were treated for portal hypertension by esophageal varices ligation in 13 cases and by portosystemic shunt in 144 cases. The age of the patients at operation was correlated with the cause of portal hypertension : mean age was six and a half years for cases with extra-hepatic blockage, and ten years for cases with cirrhosis. In 73% of cases, the shunt was undertaken following a bleeding episode from esophageal varices; at the present time, the decision to undertake a prophylactic type of shunt would be much more questionable. Central splenorenal shunt and mesocaval shunt were the operations most frequently performed by the different surgical teams in charge of these children (respectively 69 and 47 cases). Among the postoperative complications, three cases of venous stasis in lower limbs occurred after a mesocaval shunt; one child died two and a half years after a central splenorenal shunt from pneumococcal sepsis. During the last two years, there is a tendency in our group to perform a Warren shunt for intrahepatic portal hypertension, and a mesocaval shunt with jugular vein interposition in the case of extrahepatic portal hypertension. Recurrence of bleeding from esophageal varices after simple ligation has been observed in 64% of the cases; after portosystemic shunts, the anastomosis was a success in 89.3% of the cases. Whereas a significant fall in portal pressure after completion of the anastomosis is of good prognostic value, the fact that in some cases intraoperative measurement of pressure before and after shunting may show no difference does not imply a secondary thrombosis of the anastomosis, since this complication was seen in only 13% of the cases in these conditions.
Nimer, Assy; M, Paizi; D, Gaitini; Y, Baruch; G, Spira
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
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
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
Lin, G; Lunderquist, A; Hägerstrand, I
Twenty-two postmortem specimens of the liver (18 normal livers, three with liver metastases, and one with liver cirrhosis) with attached ligamenta teres were investigated using silicone rubber injection technique. In all cases, the paraumbilical veins were demonstrated. They were usually divided into 2 groups, one on the right and one on the left side of the ligamentum teres, and they terminated in a variable manner into small peripheral portal vein branches in the liver parenchyma. A patent segment of the umbilical vein was found in 7 of the 22 cases. Connections between the umbilical vein and paraumbilical veins were supposed to represent one of the collateral channels in portal hypertension.
Twenty-one postmortem specimens of the liver (18 normal livers, 3 liver metastases) with attached ligamentum teres were investigated using silicone rubber injection technique. In all cases, the paraumbilical veins were demonstrated. They were usually divided into 2 groups, one on the right and the other on the left side of the ligamentum teres, and they terminated in a variable manner into small peripheral portal vein branches in the liver parenchyma. A patent proximal segment of the umbilical vein was found in 7 of the 21 cases. Connections between the umbilical vein and paraumbilical veins were supposed to represent one of the collateral channels in portal hypertension.
Sze, Daniel Y; Magsamen, Karl E; McClenathan, James H; Keeffe, Emmet B; Dake, Michael D
Caput medusa is a frequent incidental finding in patients with portal hypertension that usually represents paraumbilical vein portosystemic collateral vessels draining into body wall systemic veins. A symptomatic caput medusa was seen in a morbidly obese patient after an umbilical hernia repair, which was fed not by the left portal vein but by the left gastroepiploic vein, in a recurrent adhesed umbilical hernia that likely contained herniated omentum. Refractory hemorrhage from this caput medusa was successfully treated by transjugular intrahepatic portosystemic shunt creation and balloon-occluded variceal sclerosis.
Dragoteanu, Mircea; Balea, Ioan A; Dina, Liliana A; Piglesan, Cecilia D; Grigorescu, Ioana; Tamas, Stefan; Cotul, Sabin O
AIM: To explore portal hypertension and portosystemic shunts and to stage chronic liver disease (CLD) based on the pathophysiology of portal hemodynamics. METHODS: Per-rectal portal scintigraphy (PRPS) was performed on 312 patients with CLD and liver angioscintigraphy (LAS) on 231 of them. The control group included 25 healthy subjects. We developed a new model of PRPS interpretation by introducing two new parameters, the liver transit time (LTT) and the circulation time between right heart and liver (RHLT). LTT for each lobe was used to evaluate the early portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing portal inflow. We calculated the classical per-rectal portal shunt index (PRSI) at PRPS and the hepatic perfusion index (HPI) at LAS. RESULTS: The normal LTT value was 24 ± 1 s. Abnormal LTT had PPV = 100% for CLD. Twenty-seven non-cirrhotic patients had LTT increased up to 35 s (median 27 s). RHLT (42 ± 1 s) was not related to liver disease. Cirrhosis could be excluded in all patients with PRSI < 5% (P < 0.01). PRSI > 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal (LTT = 24 s, PRSI < 5%). In stage 1, LTT is increased, while PRSI remains normal. In stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the patients with PRSI > 30%. RHLT and HPI were used to subtype stage 4. In our study stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD, stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis, stage 4 had PPV = 100% for cirrhosis. CONCLUSION: LTT allows the detection of early portal hypertension and of opening of transhepatic shunts. PRSI is useful in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stages the
Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei
AIM: To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. METHODS: Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. RESULTS: In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. CONCLUSION: It is feasible to establish an
Futagawa, S.; Fukazawa, M.; Musha, H.
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.
Luigiano, Carmelo; Iabichino, Giuseppe; Judica, Antonino; Virgilio, Clara; Peta, Valentina; Abenavoli, Ludovico
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
Seo, Yeon Seok; Shah, Vijay H
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.
Porres-Aguilar, M; Gallegos-Orozco, J F; Garcia, H; Aguirre, J; Macias-Rodriguez, R U; Torre-Delgadillo, A
Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.
Chan, Carlos; Zenteno-Guichard, Gustavo; Vásques, Moisés; Hernández, Jorge; Orozco, Héctor
Background Hemorrhagic portal hypertension, secondary to both intrahepatic and extrahepatic portal hypertension, is an uncommon entity. In this condition, the extrahepatic and the intrahepatic obstruction of the portal vein, due to chronic liver disease, produce a more severe form of hemorrhagic portal hypertension that is more difficult to control. The results of surgical treatment (modified Sugiura- Futagawa operation) in this subset of patients is analyzed. Methods Among 714 patients with a history of hemorrhagic portal hypertension, 14 cases were found with histologically proven liver cirrhosis and complete splenomesoportal thrombosis demonstrated by means of preoperative angiography. Patients with incomplete (partial) splenomesoportal thrombosis were excluded. There were nine males and 5 females with a mean age of 51 years. Alcoholic cirrhosis was demonstrated in 50% of the cases, post hepatitic cirrhosis in 28%, primary biliary cirrhosis in 7%, and cryptogenic cirrhosis in 14%. There were nine Child-Pugh A and 5 B cases. All cases were treated by means of our modified Sugiura-Futagawa procedure. Results Bleeding recurrence from esophagogastric varices was shown in one case, colonic varices in one case and hypertensive gastropathy in another of the survivors. Post operative encephalopathy was shown in 3 of the cases. The thirty-six month survival rate was 30% (Kaplan-Meier). Conclusions The combination of intrahepatic plus extrahepatic portal hypertension has a worse prognosis. Treatment options are limited (sclerotherapy and/or devascularization), because shunt surgery, TIPS and liver transplantation have a very restricted role and postoperative outcome is poor. PMID:10371060
Ul'rikh, E V; Korolev, M P; Kupatadze, F D; Sevriugov, B L; Nabokov, V V
The authors have performed 28 sessions of endoscopic sclerotherapy of dilated esophagus veins in children. The 70% ethyl alcohol was used. Six sessions were carried out in patients with gastroesophageal hemorrhage. In 22 patients the sclerotherapy was carried on according to plan. The fiber gastroscope with a standard injector was used. A conclusion is made of expediency of using endoscopic sclerotherapy in complex treatment of portal hypertension in children.
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
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
Şirli, Roxana; Sporea, Ioan; Popescu, Alina; Dănilă, Mirela
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
Imai, Miwa Akasofu; Kawahara, Ei; Katsuda, Shogo; Yamashita, Tatsuya
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.
Zaher, Tarik; Ibrahim, Islam; Ibrahim, Amany
Portal hypertension is common in Egypt as a sequela to the high prevalence of hepatitis C virus and bilharziasis. In portal hypertension internal haemorrhoids are frequently found. The aim of this work was to compare the outcome of endoscopic band ligation (EBL) of symptomatic internal haemorrhoids with that of stapled haemorrhoidopexy (SH) in Egyptian patients with portal hypertension. In this study, 26 portal hypertensive patients (with oesophageal and/or fundal varices) with a grade 2-4 internal haemorrhoids who had no coagulation disorders were randomised to treatment by EBL (13 patients) or SH (13 patients) after doing colonoscopy. Symptom scores of bleeding and prolapse were assessed before and after the intervention. Complications were recorded. Patients were followed up for 12months. Goligher's grades of internal haemorrhoids improved significantly (p=0.018) 12weeks after SH (from 2.9±0.8 to 0.4±0.5; p=0.001) and after EBL (from 2.8±0.8 to 1.1±0.8; p=0.001). Symptom (bleeding and prolapse) scores significantly improved 4weeks after both EBL (from 1.6±0.8 to 0.6±0.8; p<0.001 and from 1.6±0.9 to 0.5±0.5; p=0.002, respectively) and SH (from 1.8±0.8 to 0.2±0.4; p=0.002 and from 1.5±0.9 to 0.2±0.4; p=0.001, respectively). The differences after 4weeks between EBL and SH were not significant (p=0.168 and p=0.225). Pain requiring analgesics occurred in five patients (38.5%) after EBL, compared with six (46.2%) after SH (p=0.691). Minimal bleeding occurred in two patients (15.4%) after EBL but not with SH; urinary retention was observed in one patient after EBL compared with two after SH; and anal fissures were observed in one patient after EBL. During 1-year follow-up, increased frequency of stool occurred in one patient after EBL. Recurrence of symptoms was observed in three patients after EBL and in one after SH. For portal hypertensive patients with internal haemorrhoids and without coagulation disorders SH seems to be superior to EBL. However
Duché, Mathieu; Ducot, Béatrice; Ackermann, Oanez; Guérin, Florent; Jacquemin, Emmanuel; Bernard, Olivier
Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child's age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can
Annet, Laurence; Materne, Roland; Danse, Etienne; Jamart, Jacques; Horsmans, Yves; Van Beers, Bernard E
To determine the correlations between hemodynamic parameters of hepatic flow measured with magnetic resonance (MR) imaging and Doppler ultrasonography (US) and the severity of cirrhosis and portal hypertension. Forty-six patients referred for measurements of portal venous pressure (three with normal liver, 12 with chronic hepatitis, and 31 with cirrhosis [10 with Child-Pugh class A cirrhosis; 13 with class B cirrhosis; and eight with class C cirrhosis]) were included in the study. Apparent liver perfusion, apparent arterial and portal perfusion, portal fraction, distribution volume, and mean transit time were measured with dynamic contrast material-enhanced MR imaging. Portal velocity, portal flow, congestion index, right hepatic artery resistance index, and modified hepatic index were measured with Doppler US. Results in patients with cirrhosis and those without cirrhosis were compared with the Wilcoxon rank sum test. Correlations were assessed with Spearman rank correlation coefficients. With MR imaging, all flow parameters except distribution volume were significantly different between patients with and those without cirrhosis (P <.05). There was a significant correlation between all flow parameters measured with MR imaging and portal pressure (P <.02). Apparent arterial (P =.024) and portal (P <.001) perfusion, portal fraction (P <.001), and mean transit time (P =.004) were correlated with Child-Pugh class. Flow parameters measured with Doppler US did not differ significantly between patients with and those without cirrhosis. Only right hepatic arterial resistance (P <.007) and portal flow (P <.043) were weakly (r < 0.7) correlated with portal pressure. No Doppler US parameter was correlated with Child-Pugh class. Hepatic flow parameters measured with MR imaging correlate with the severity of cirrhosis and portal hypertension. Doppler US parameters are only weakly correlated with portal pressure. Copyright RSNA, 2003
Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J
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 non-bleeding 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.
Gil, A; Martínez-Regueira, F; Hernández-Lizoain, J L; Pardo, F; Olea, J M; Bastarrika, G; Cienfuegos, J A; Bilbao, J I
Major abdominal surgery can be contraindicated in some cirrhotic patients because of severe portal hypertension. The present study reports our experience of three patients with abdominal tumours prepared for surgery by transjugular intrahepatic portosystemic shunts (TIPS) in order to reduce portal hypertension and the risk of intraoperative bleeding. Three patients with cirrhosis and portal hypertension diagnosed with a right colon carcinoma, an adenocarcinoma of pancreas and a gastric and sigmoid synchronic tumours in the same patient. Because portal hypertension was the leading cause of surgical contraindication, neoadjuvant TIPS placement was proposed before surgery. TIPS placement was performed without intra-procedure complications. An average reduction of 18 mmHg was achieved in portosystemic gradients. The planned operations were performed with a delay of 14-45 days after TIPS without intraoperative bleeding. Complications occurred in one patient without operative mortality. TIPS placement allows a pre-operative portal decompression in cirrhotic patients with portal hypertension and abdominal tumours that require surgical treatment. This procedure reduces the risk of bleeding by reducing the portosystemic gradient and the varices around the tumoral area. This procedure is less invasive than conventional shunt surgery, but it is not free of complications and should be performed by experienced interventional radiologists on selected patients. This is still an experimental indication of TIPS which efficacy must be confirmed in larger series.
Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J
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
Huet, Pierre-Michel; Vincent, Catherine; Deslauriers, Julie; Coté, Jean; Fenyves, Daphna; Matsutani, Shoichi; Boileau, Robert; Kerckvoorde, Jacline Huet-Van
Portal hypertension is not a rare complication of PBC, but there are no useful clinical predictors of its severity. In fact, in PBC patients, the evaluation of portal hypertension needs a direct access to the portal vein in order to measure the real porto-hepatic gradient (PHG), mainly because of a possible pre-sinusoidal component. The severity of portal hypertension, as measured by the PHG using a thin needle, correlated significantly with the long-term survival of PBC patients, but the initial Mayo score remained the best predictor of survival. In addition to the well-known effects on biological parameters, ursodeoxycholic acid (UDCA) treatment has been associated with a stabilization or improvement of portal hypertension but this effect was not observed in all patients: "responders" and "non-responders" to the UDCA could be identified according to changes in PHG and aspartate aminotransferase (AST) levels observed 2 years after UDCA therapy and had significantly different long-term survivals. This notion of "responders" and "non-responders" is new and may well explain the conflicting data found in the literature concerning the effects of UDCA in PBC patients as reported in various clinical trials. These findings are of interest when considering the emerging non-invasive methods aimed at evaluating liver fibrosis, particularly elastography that may prove useful in the indirect assessment of portal hypertension in the near future, therefore avoiding the need for the invasive measurement of the PHG.
Iwao, T; Oho, K; Nakano, R; Yamawaki, M; Sakai, T; Sato, M; Miyamoto, Y; Sakai, K; Sata, M; Toyonaga, A
The aim of this study was to compare postprandial hemodynamic changes observed during assumption of the recumbent posture and upright posture in patients with cirrhosis and portal hypertension. Eleven patients with cirrhosis and portal hypertension were studied. Echo-Doppler examinations were performed to measure flow volume in the portal vein (PV), superior mesenteric artery (SMA), and splenic artery (SA) in the fasting condition. Collateral blood flow was indirectly calculated by determining the difference between the sum of SMA, SA, and PV blood flows. After these measurements were done, each patient received a standardized liquid meal and was then randomly assigned to either maintain supine or upright posture, in a crossover design, on 2 different days (recumbent day and upright day). On each study day, the above-mentioned measurements were repeated 30 min and 60 min after the meal. PV blood flow increased significantly after the meal on the recumbent day (P < 0.01) but not on the upright day (P = 0.78). Although there were significant postprandial increases in SMA blood flow on both study days (P < 0.01, P < 0.01), the effect was less pronounced on the upright day than on the recumbent day (P < 0.01). Postprandial SA blood flow showed no change on the recumbent day (P = 0.64), but decreased significantly on the upright day (P < 0.01). The calculated postprandial collateral blood flow increased significantly on the recumbent day (P < 0.05), but showed no change on the upright day (P = 0.53). These results suggest that the upright posture blunts postprandial splanchnic hyperemia in patients with cirrhosis and portal hypertension.
Gamero, María T; Gallardo, María Susana; Aguilar, Víctor; Bravo, Eduar; Guevara, Julissa; Mejia, Fernando
Liver involvement is usually seen in patients infected with the human immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B or C, in alcohol abuse, etc. However, there is a group of patients who develop liver involvement and portal hypertension of unspecified cause. Non-cirrhotic portal hypertension (NCPH) is a liver disorder recently described, but potentially serious. It has been reported in HIV-infected patients with highly active antiretroviral therapy (HAART), specifically didanosine (DDI). The pathophysiology involves the infectious agent (HIV) and its treatment (HAART), since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection produces a prothrombotic state by protein S deficiency leading to the obliteration of small hepatic venules. It has been postulated that DDI as a cofactor in the pathogenesis of NCPH. All this leads that many of the liver biopsies show nodular regenerative hyperplasia. We present the case of a HIV-infected patient who was treated with a longstanding DDI. She developed upper gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was confirmed by biopsy. However, there is no similar study in our country.
Witte, Marlys H.; Pond, Gerald D.
Although restricted transhepatic portal flow is necessary for development of generalized portal hypertension (GPH), increased splanchnic arterial inflow also contributes to GPH and its clinical sequelae. In this context, we describe 7 male and 6 female patients (mean age 48 years) in whom the lesser splanchnic (gastrosplenic) system played a key role in the signs and symptoms of GPH. These 13 patients (9 with hepatic cirrhosis, 3 with primary myeloproliferative disorder, and 1 with extrahepatic portal block) shared common features of massive splenomegaly, huge splenofundic gastric varices, often with a prominent natural shunt to the left renal vein. Total or near total splenectomy alone or combined where appropriate with coronary vein ligation was effective in controlling varix hemorrhage (10 patients), ascites (3), or complications of an enlarged spleen-anorexia and abdominal pain (3), hemolytic anemia (1) and profound thrombocytopenia with severe epistaxis (1). Intraoperative jejunal portal venography was crucial in operative management in order to establish definitively the presence or absence of coronary venous collaterals, and when present, to verify their operative ligation. These distinctive patients illustrate: 1) GPH is a heterogeneous syndrome of divergent splanchnic circulatory patterns, a feature which should be taken into account in selecting operative treatment; 2) one well-defined subgroup displays prominent hyperdynamic lesser splanchnic and specifically, splenic blood flow as a major contributor to clinical complications; and 3) within this subgroup, splenectomy combined with documented absence or surgical interruption of coronary venous collaterals as corroborated by intraoperative portography is effective alternative treatment. PMID:2278922
Kimura, Debora Conte; Nagaoka, Marcia Regina; Borges, Durval Rosa; Kouyoumdjian, Maria
AIM To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS). On the other hand, the PHR induced by Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngII was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION AngII and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngII; the diminished glucose release induced by AngII in SHR is not related to glycogen content. PMID:28660012
Fahmy, Mona E.; Osman, Mahmoud A.; Mahmoud, Rehab A.; Mohamed, Lamiaa K.; Seif-elnasr, Khaled I.; Eskander, Ayman E.
Background/Aim: Among the various methods for evaluating gastric emptying, the real-time ultrasound is safe, does not require intubation, or rely on either radiologic or radionuclide technique. The aim of our work was to measure the gastric emptying in pediatric patients with portal hypertension by using the real-time ultrasound. Patients and Methods: Forty patients with portal hypertension with mean age 7 ± 2.8 years and 20 healthy children as a control group underwent gastric emptying study by using real-time ultrasound. The cross-sectional area of the gastric antrum was measured in the fasting state and then each subject was allowed to drink tap water then calculated by using formula area (π longitudinal × anteroposterior diameter/4). The intragastric volume was assumed to be directly proportional to the cross-sectional area of the antrum. Results: The mean gastric emptying half-time volume was significantly delayed in portal hypertension patients (40 ± 6.8 min) compared with the control subjects (27.1 ± 3.6) min (P<0.05). Patients with extrahepatic portal vein obstruction had significant delayed gastric emptying in comparison to patients with portal hypertension due to other etiologies (36.14 ± 4.9 vs 44.41 ± 6.04 min; P<0.01). Conclusion: Ultrasound is a noninvasive and a reliable method for measuring gastric emptying in pediatric patients. Gastric emptying was significantly delayed in patients with portal hypertension. Etiology of portal hypertension may influence gastric emptying time in patients with chronic liver disease. PMID:22249091
Shi, Min; Wei, Jue; Meng, Wen-Ying; Wang, Na; Wang, Ting; Wang, Yu-Gang
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
Shi, Min; Wei, Jue; Meng, Wen-Ying; Wang, Na; Wang, Ting; Wang, Yu-Gang
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
Fei, Yang; Li, Wei-Qin; Zong, Guang-Quan; Chen, Jian; Wang, Wei
To discover whether cirrhotic portal hypertension patients with symptomatic cholelithiasis would benefit from cholecystolithotomy combined with Armillarisin A in the authors hospital. Methods: Sixty-one patients with cirrhotic portal hypertension and symptomatic gallstone disease who underwent either cholecystolithotomy combined with Armillarisin A (group A) or cholecystectomy (group B) for cholelithiasis from Feb 2007 to March 2011 were retrospectively reviewed. These patients were undergoing simultaneous procedure for esophageal varices. The operation-relevant information, change of laboratory examination data, postoperative complications and symptoms were analyzed. Results: There were no significant differences between group A and group B in mean operative time, intraoperative blood loss, time to resume diet postoperatively and length of hospital stay (P 0.05). The hepatic function biochemical profile and Child-Pugh's score at 2 weeks and 1 month after operations were both altered significantly less in group A than in group B (ALT, 0.008, 0.011; AST, 0.006, 0.003; Child-Pugh's score, 0.010, 0.016, respectively). However, at 6 months postoperatively, the changes were not significant (P 0.05). Except for gallstone recurrence and wound infection, occurrences or development of postoperative complications including biliary fistula, liver failure and subphrenic infection showed significant differences between the two groups (P = 0.037, P = 0.041, P = 0.019, respectively). After a mean follow-up of 4.2 years, all patients remain alive. Twenty-seven patients in group A (93%) are free of biliary symptoms. Cholecystolithotomy combined with using Armillarisin A is a useful treatment for symptomatic gallstones in patients with cirrhotic portal hypertension who are at high risk for cholecystectomy. It preserves gallbladder function and reduces the possibility of liver failure; moreover the rate of recurrent gallstones are relatively low. Celsius.
Ripoll, Cristina; Garcia-Tsao, Guadalupe
Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct gastric mucosal lesions that may cause acute and/or chronic upper gastrointestinal hemorrhage in patients with cirrhosis. Whereas PHG is associated with portal hypertension, GAVE may present in patients without portal hypertension or liver disease. Diagnosis is made upon visualization of the characteristic lesions with upper gastrointestinal endoscopy, although the differential may be difficult at times. PHG is characterized endoscopically by a mosaic pattern with or without red signs and a proximal distribution. PHG mainly causes chronic blood loss and anemia in patients with cirrhosis but also can cause acute hemorrhage. First-line therapy for chronic hemorrhage from PHG is a nonselective beta-blocker (propranolol or nadolol) and iron supplementation. If bleeding/anemia are not controlled with these measures and the patient is transfusion-dependent, shunt therapy (transjugular intrahepatic portosystemic shunt or shunt surgery) should be considered. Management of acute bleeding from PHG, an infrequent event, should be accomplished with a vasoactive drug, somatostatin (or its analogues) or terlipressin. If bleeding responds, the patient must be switched to a nonselective beta-blocker. Shunt therapy should be considered in patients who rebleed or continue to bleed despite adequate beta-blocker therapy. GAVE is less common than PHG. It is characterized by red spots without a background mosaic pattern, typically in the gastric antrum. When lesions have a linear distribution, the lesion is called "watermelon stomach." GAVE is a cause of chronic gastrointestinal bleeding and anemia in patients with cirrhosis. If lesions are localized, first-line therapy is argon plasma coagulation. In more diffuse lesions, therapy with argon plasma coagulation is more complicated. Preliminary data suggest that cryotherapy may be a reasonable option for diffuse GAVE lesions. Neither beta
Aday, Ariel W; Mayo, Marlyn J; Elliott, Alan; Rockey, Don C
Patients with cirrhosis and portal hypertensive complications have reduced survival. As such, it has been suggested that nonselective beta-blocker therapy in patients with advanced ascites is harmful. The aim of this study was, therefore, to determine the risk of mortality in patients with cirrhosis and ascites taking nonselective beta-blocker therapy for the prevention of variceal hemorrhage. This study was a retrospective analysis of 2,419 patients with cirrhosis and portal hypertension admitted to Parkland Memorial Hospital (a university-affiliated county teaching hospital) from 2003-2010. Patients were subdivided into those with varices only, ascites only and those with both varices and ascites. The primary outcome measure for this study was all-cause in-hospital mortality. Overall, 68 of 1,039 (6.5%) patients taking beta-blockers died during their hospitalization, while 223 of 1,380 (16.2%) patients not taking beta-blockers died (P < 0.001). Beta-blocker use was also assessed in specific cohorts; mortality was 21.1% in patients with severe ascites with varices who were not taking beta-blockers compared with 8.9% in patients who were taking beta-blockers (P = 0.05). Overall, fewer patients taking beta-blockers died compared with those not taking beta-blockers in patients with varices only (6.4% versus 12.1%) and those with ascites with or without varices (6.6% versus 18.1%) (P < 0.001). Mortality was lower in patients with cirrhosis and portal hypertension taking nonselective beta-blockers than in those not taking beta-blockers. The use of nonselective beta-blockers provided a significant survival benefit in patients with all grades of ascites, including those with severe ascites. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
Lee, Pei-Chang; Yang, Ying-Ying; Lee, Wei-Ping; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Lee, Tzung-Yan; Lin, Han-Chieh
Vitamin D₃ improves portal hypertension (PH) through the activation of vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) in cirrhotic rats. Propranolol is a non-selective β-blocker that is recommended for the treatment of PH. The present study aims to investigate the detail systemic and hepatic mechanisms of vitamin D₃ and propranolol, alone or in combination, in cirrhotic rats. Common bile duct-ligated and thioacetamide cirrhotic rats were treated with vehicle, propranolol (30 mg/kg/day), vitamin D₃ (0.5 μg/100 g/day, twice weekly), or propranolol + vitamin D₃, separately. Significantly, propranolol and vitamin D₃ produced a similar magnitude of reduction in portal venous pressure (PVP) in cirrhotic rats through different mechanisms: whereas propranolol decreased PVP by reducing splanchnic hyperemia and cardiac index, vitamin D₃ decreased PVP by decreasing intrahepatic resistance (IHR). However, propranolol + vitamin D₃ did not further decrease PVP in cirrhotic rats. Notably, a marked decrease in hepatic VDR and CaSR expressions was noted in cirrhotic human/rat livers compared with non-cirrhotic human/rat livers. In cirrhotic rats, vitamin D₃ administration decreasing IHR by inhibiting the renin-angiotensin system, hepatic oxidative stress, inflammation/fibrosis, angiotensin II (ANGII) production, CaSR-mediated ANGII hyperresponsiveness, ANGII-induced hepatic stellate cells contraction, and correcting hepatic endothelial dysfunction through upregulation of hepatic VDR, CaSR, and endothelial nitric oxide synthase expressions. Chronic vitamin D₃ treatment alone results in comparative portal hypotensive effects as propranolol alone in cirrhotic rats with PH. Taken together, chronic vitamin D₃ administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side-effects. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor
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
Cai, Y; Deng, X; Zhou, X; Zheng, Y; Wang, X; Liang, B; Cai, Q; Yang, Y
The mechanism of hypoxic moderation of systemic systolic blood pressure was investigated in spontaneously hypertensive rats (SHR). Male SHR rats were divided into hypoxic (H, 5000 m for 15 d) and normoxic (N) groups. The systemic blood pressure of SHR-H (24.9 +/- 1.2 kPa) was found to be 3 kPa lower than that in SHR-N (27.0 +/- 1.3 kPa) (P < 0.05). This protective effect may have been related to the adaptive changes in vascular reactivity which manifested as an increase in the relaxation response of the aorta to ACh (P < 0.01) and a drop in its contraction in response to 5-HT (P < 0.05) following hypoxic exposure. The hypoxic moderating effect against the development of systemic hypertension may have also been related to the increased plasma levels of ANP observed.
Introduction We report for the first time a unique case of VACTERL (vertebral anomalies, anal atresia or imperforate anus, cardiac anomalies, tracheoesophageal fistula, renal and limb defect) spectrum associated with portal hypertension. The occurrence of both VACTERL spectrum and extrahepatic portal hypertension in a patient has not been reported in the literature. We examined whether or not there was any association between extrahepatic portal hypertension and VACTERL spectrum. Case Presentation A two-and-half-year-old Caucasian girl with VACTERL spectrum presented with hematemesis and abdominal distension. She had caput medusae, ascites, splenomegaly, gastric and esophageal varices. Her liver function tests were within normal limits. Magnetic resonance imaging of the liver with contrast showed a thready portal vein with collateral vessels involving both right and left portal veins without intrahepatic duct dilation. Conclusion A thready portal vein, with features of extrahepatic portal hypertension, is a rare non- VACTERL-type defect in patients with VACTERL spectrum. Understandably, clinicians should give low priority to looking for portal hypertension in VACTERL spectrum patients presenting with gastrointestinal bleeding. However before routinely looking for a thready portal vein and/or extrahepatic portal hypertension in asymptomatic VACTERL spectrum patients, we need further evidence to support this rare association. PMID:20444267
Bhurtel, Dilli Raj; Losa, Ignatius
We report for the first time a unique case of VACTERL (vertebral anomalies, anal atresia or imperforate anus, cardiac anomalies, tracheoesophageal fistula, renal and limb defect) spectrum associated with portal hypertension. The occurrence of both VACTERL spectrum and extrahepatic portal hypertension in a patient has not been reported in the literature. We examined whether or not there was any association between extrahepatic portal hypertension and VACTERL spectrum. A two-and-half-year-old Caucasian girl with VACTERL spectrum presented with hematemesis and abdominal distension. She had caput medusae, ascites, splenomegaly, gastric and esophageal varices. Her liver function tests were within normal limits. Magnetic resonance imaging of the liver with contrast showed a thready portal vein with collateral vessels involving both right and left portal veins without intrahepatic duct dilation. A thready portal vein, with features of extrahepatic portal hypertension, is a rare non- VACTERL-type defect in patients with VACTERL spectrum. Understandably, clinicians should give low priority to looking for portal hypertension in VACTERL spectrum patients presenting with gastrointestinal bleeding. However before routinely looking for a thready portal vein and/or extrahepatic portal hypertension in asymptomatic VACTERL spectrum patients, we need further evidence to support this rare association.
Experimental evidence suggests that innervation can exert a long-term control and modulation on effector cell homeostasis. These trophic influences are known to occur between the motor innervation and skeletal muscles, tissues in which these phenomena have been well studied. A similar picture is also emerging to indicate that smooth muscles may be subjected to a neurotrophic influence. The present paper reviews and presents data obtained after chemical sympathectomy of rat portal vein with 6-hydroxydopamine. Basically three experimental protocols were utilized: 1) studies before and after complete in vitro denervation, using the vessel as its own control; 2) in vivo sympathectomy followed by in vitro studies at various times thereafter; and 3) experiments in which the veins were denervated in vitro, placed in organ culture, and treated with either norepinephrine (NE) or the vehicle. The results indicate that in rat portal vein the sympathetic innervation normally exerts a trophic influence mediated, at least in part, by NE. This evidence is discussed in relation to other smooth muscles insofar as supersensitivity mechanisms and other possible effects triggered by transmitter withdrawal. The discussion is extended to encompass ways by which NE could exert its effects, and the possibility of other trophic factors.
Jansen, Christian; Eischeid, Hannah; Goertzen, Jan; Schierwagen, Robert; Anadol, Evrim; Strassburg, Christian P; Sauerbruch, Tilman; Odenthal, Margarete; Trebicka, Jonel
Circulating miRNA-34a is increased in blood of patients with different liver diseases when compared to healthy controls. However, the origin of miRNA-34a and its possible relationship with hemodynamics and outcome in cirrhotic patients with portal hypertension is unknown. We analyzed the levels of miRNA-34a in cirrhotic patients with severe portal hypertension. We included 60 cirrhotic patients receiving TIPS for prevention of rebleeding and/or therapy-refractory ascites. miRNA-34a levels were measured using qPCR and normalized by SV-40 in the portal and hepatic venous blood of these patients taken at TIPS procedure. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up. Levels of miRNA-34a were higher in the hepatic vein than in the portal vein. Circulating miRNA-34a in the hepatic vein correlated with ALT, CHE and sodium excretion after TIPS. miRNA-34a showed no correlation with portal pressure, but its levels in the portal vein correlated inversely with the congestion index. Interestingly, the levels of miRNA-34a in the portal and hepatic vein showed inverse correlation with arterial pressure. Furthermore, levels of miRNA-34a in the hepatic vein had a predictive value for survival, but MELD, creatinine at short-time follow-up 14 days after TIPS-insertion and portal pressure after TIPS performed better. This study demonstrates for the first time, that miRNA-34a may originate to a large extent from the liver. Even though higher levels of miRNA-34a are possibly associated with better survival at long-term follow-up in cirrhotic patients with severe portal hypertension receiving TIPS, classical prognostic parameters predict the survival better.
Jansen, Christian; Eischeid, Hannah; Goertzen, Jan; Schierwagen, Robert; Anadol, Evrim; Strassburg, Christian P.; Sauerbruch, Tilman; Odenthal, Margarete; Trebicka, Jonel
Background Circulating miRNA-34a is increased in blood of patients with different liver diseases when compared to healthy controls. However, the origin of miRNA-34a and its possible relationship with hemodynamics and outcome in cirrhotic patients with portal hypertension is unknown. We analyzed the levels of miRNA-34a in cirrhotic patients with severe portal hypertension. Methods We included 60 cirrhotic patients receiving TIPS for prevention of rebleeding and/or therapy-refractory ascites. miRNA-34a levels were measured using qPCR and normalized by SV-40 in the portal and hepatic venous blood of these patients taken at TIPS procedure. Hemodynamic and clinical parameters were assessed before TIPS and during follow-up. Results Levels of miRNA-34a were higher in the hepatic vein than in the portal vein. Circulating miRNA-34a in the hepatic vein correlated with ALT, CHE and sodium excretion after TIPS. miRNA-34a showed no correlation with portal pressure, but its levels in the portal vein correlated inversely with the congestion index. Interestingly, the levels of miRNA-34a in the portal and hepatic vein showed inverse correlation with arterial pressure. Furthermore, levels of miRNA-34a in the hepatic vein had a predictive value for survival, but MELD, creatinine at short-time follow-up 14 days after TIPS-insertion and portal pressure after TIPS performed better. Conclusion This study demonstrates for the first time, that miRNA-34a may originate to a large extent from the liver. Even though higher levels of miRNA-34a are possibly associated with better survival at long-term follow-up in cirrhotic patients with severe portal hypertension receiving TIPS, classical prognostic parameters predict the survival better. PMID:25068403
Alwmark, A; Bengmark, S; Gullstrand, P; Joelsson, B; Lunderquist, A; Owman, T
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
Hakim, Seifeldin; Bortman, Jared; Orosey, Molly; Cappell, Mitchell S.
Abstract Introduction: A novel case is reported of upper gastrointestinal (UGI) bleeding from sinistral portal hypertension, caused by a left gastric artery (LGA) pseudoaneurysm (PA) compressing the splenic vein (SV) that was successfully treated with PA embolization. Case report: A 41-year-old man with previous medical history of recurrent, alcoholic pancreatitis presented with several episodes of hematemesis and abdominal pain for 48 hours. Physical examination revealed a soft abdomen, with no abdominal bruit, no pulsatile abdominal mass, and no stigmata of chronic liver disease. The hemoglobin declined acutely from 12.3 to 9.3 g/dL. Biochemical parameters of liver function and routine coagulation profile were entirely within normal limits. Abdominal CT revealed a 5-cm-wide peripancreatic mass compressing the stomach and constricting the SV. Esophagogastroduodenoscopy showed blood oozing from portal hypertensive gastropathy, small nonbleeding gastric cardial and fundal varices, gastric compression from the extrinsic mass, and no esophageal varices. MRCP and angiography showed that the mass was vascular, arose from the LGA, compressed the mid SV without SV thrombosis, and caused sinistral portal hypertension. At angiography, the PA was angioembolized and occluded. The patient has been asymptomatic with no further bleeding and a stable hemoglobin level during 8 weeks of follow-up. Discussion: Literature review of the 14 reported cases of LGA PA revealed that this report of acute UGI bleeding from sinistral portal hypertension from a LGA PA constricting the SV is novel; one previously reported patient had severe anemia without acute UGI bleeding associated with sinistral portal hypertension from a LGA PA. Conclusion: A patient presented with UGI bleeding from sinistral portal hypertension from a LGA PA compressing the SV that was treated by angiographic obliteration of the PA which relieved the SV compression and arrested the UGI bleeding. Primary therapy for
Morishita, Keitaro; Hiramoto, Akira; Michishita, Asuka; Takagi, Satoshi; Hoshino, Yuki; Itami, Takaharu; Lim, Sue Yee; Osuga, Tatsuyuki; Nakamura, Sayuri; Ochiai, Kenji; Nakamura, Kensuke; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi
OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.
Dave, Jaydev K; Liu, Ji-Bin; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Merton, Daniel A; Machado, Priscilla; Zhao, Hongjia; Altemus, Joseph; Needleman, Laurence; Brown, Daniel B; Forsberg, Flemming
Effective animal models are needed to evaluate the feasibility of new techniques to assess portal hypertension (PH). Here we developed 2 canine models of acute PH by increasing intrasinusoidal resistance and by increasing the portal vein (PV) flow volume to test the efficacy of a noninvasive technique to evaluate PH. The acute low-flow PH model was based on embolization of liver circulation by using a gelatin sponge material. The acute high-flow PH model was based on increasing the PV flow volume by using an arteriovenous (A-V) shunt from the femoral artery and saline infusion. PV pressures and diameters were assessed before and after inducing PH. Pressure values and diameters were obtained from the inferior vena cava in 3 unmanipulated controls. The low-flow model of PH was repeatable and successfully increased PV pressure by an average of 16.5 mm Hg within 15 min. The high-flow model of PH failed to achieve increased PV pressures. However, saline supplementation of the portal circulation in the high-flow model led to mean increases in PV pressures of 12.8 mm Hg within 20 min. Pulsatility in the PV was decreased in the low-flow model and increased in the high-flow model relative to baseline. No changes in PV diameter were noted in either model. These acute PH models are relatively straightforward to implement and may facilitate the evaluation of new techniques to assess PH. PMID:23114046
Dave, Jaydev K; Liu, Ji-Bin; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Merton, Daniel A; Machado, Priscilla; Zhao, Hongjia; Altemus, Joseph; Needleman, Laurence; Brown, Daniel B; Forsberg, Flemming
Effective animal models are needed to evaluate the feasibility of new techniques to assess portal hypertension (PH). Here we developed 2 canine models of acute PH by increasing intrasinusoidal resistance and by increasing the portal vein (PV) flow volume to test the efficacy of a noninvasive technique to evaluate PH. The acute low-flow PH model was based on embolization of liver circulation by using a gelatin sponge material. The acute high-flow PH model was based on increasing the PV flow volume by using an arteriovenous (A-V) shunt from the femoral artery and saline infusion. PV pressures and diameters were assessed before and after inducing PH. Pressure values and diameters were obtained from the inferior vena cava in 3 unmanipulated controls. The low-flow model of PH was repeatable and successfully increased PV pressure by an average of 16.5 mm Hg within 15 min. The high-flow model of PH failed to achieve increased PV pressures. However, saline supplementation of the portal circulation in the high-flow model led to mean increases in PV pressures of 12.8 mm Hg within 20 min. Pulsatility in the PV was decreased in the low-flow model and increased in the high-flow model relative to baseline. No changes in PV diameter were noted in either model. These acute PH models are relatively straightforward to implement and may facilitate the evaluation of new techniques to assess PH.
Ozturk, Omer; Eldem, Gonca; Peynircioglu, Bora; Kav, Taylan; Görmez, Aysegul; Cil, Barbaros Erhan; Balkancı, Ferhun; Sokmensuer, Cenk; Bayraktar, Yusuf
AIM To determine the outcomes of partial splenic embolization (PSE) for massive splenomegaly due to idiopathic portal hypertension (IPH). METHODS In this prospective study, we evaluated the characteristics and prognosis of consecutive patients with IPH who underwent PSE for all indications at a single medical center between June 2009 and January 2015. The inclusion criteria were: presence of hypersplenism, massive splenomegaly, and resultant pancytopenia. The exclusion criteria were: presence of other diseases causing portal hypertension. During the post-PSE period, the patients were hospitalized. All patients underwent abdominal computed tomography imaging 4 wk post-PSE to determine total splenic and non-infarcted splenic volumes. RESULTS A total of 11 patients, with median age of 33.27 ± 4.8 years, were included in the study. Mean spleen size was 22.9 cm (21-28 cm), and severe hypersplenism was diagnosed in all patients before PSE. Post-PSE, leukocyte and platelet counts increased significantly, reaching peak levels in the second week with gradual decreases thereafter. Liver function tests did not exhibit significant changes during post-intervention follow-up. All patients developed post-embolization syndrome, and one patient experienced serious complications; all complications were successfully treated with conservative therapy and no death occurred. CONCLUSION Our findings showed that PSE has a lower complication rate than previously-reported surgical complication rates, which supports this intervention as a viable alternative for high-risk operable patients with severe hypersplenism. PMID:27920483
Herrera, Cristina N; Tomala-Haz, Javier E
Takayasu arteritis (TA) is the third most common childhood vasculitis and its clinical manifestations depend on the arteries involved. We report a case of a 9-year-old boy with multiple aneurysms in carotid and iliac arteries, subclavian and coronary arteries, and abdominal aorta. At the age of 7 years, he presented with recurrent fever and hepatosplenomegaly. An angio-computed tomography scan showed aneurysms in the left subclavian artery, abdominal aorta, and both proximal iliac arteries. He was diagnosed with TA and was treated with corticosteroids, aspirin, and enalapril. One year later, he was admitted to Dr Roberto Gilbert Children’s Hospital because of intracranial hemorrhage. Angiography revealed enlargement of aneurysms enlargement and new aneurysms. He also developed portal hypertension. Treatment with intravenous corticosteroids, azathioprine, and monthly intravenous cyclophosphamide was begun. After 6 months of no improvement, infliximab was begun. The aim of this article was to report the concurrence of coronary involvement and portal vein hypertension in pediatric TA because there were scarce reports on this matter. PMID:27895519
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
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
Shanin, Iu N; Kotiv, B N; Tsygan, V N; Iontsev, V I
56 patients with portal hypertension were examined who underwent decompressive shunt surgery. Cardiorhytmography and integral rheography body were performed in different stages. In the late postoperative period, there were positive changes in the autonomic regulation of functions: reduced tension index and sympathetic influence on heart rhythm, increases the value of other indicators of heart rate variability. Due to an increase in heart rate and peripheral vascular resistance normalizes blood pressure while reducing the values of cardiac output. There is a further normalization of the reactivity of blood circulation: arterial pressure and vascular resistance during the functional test remained at a constant level of magnitude of shock and cardiac index significantly increased and then decreased to the level of the original values, which corresponds to the reaction apparently healthy. Disorders of regulation, state and reactivity of blood flow in portal hypertension, manifested: 1. Reduction of heart rate variability with a significant increase in sympathetic activity of autonomic nervous system. 2. Reduction of cardiac output and vascular resistance, heart rate, changes in physiological determination of hemodynamic parameters: Blood pressure is determined only by the vessel resistance. 3. Reduction of blood pressure in response to breath holding test.
Kemp, William; Colman, John; Thompson, Kenneth; Madan, Anoop; Vincent, Margaret; Chin-Dusting, Jaye; Kompa, Andrew; Krum, Henry; Roberts, Stuart
While selective intestinal decontamination (SID) can alter the hyperdynamic circulatory state of cirrhosis, the impact of SID on portal pressure remains unclear especially in the setting of clinically significant portal hypertension. To examine the impact of SID with norfloxacin on portal pressure in subjects with clinically significant portal hypertension and explore the potential mechanisms by which norfloxacin exerts its haemodynamic effects. Randomised, double blind, placebo-controlled, crossover trial of norfloxacin 400 mg twice daily for 4 weeks. The portal pressure was assessed by hepatic venous pressure gradient (HVPG). Endotoxaemia was assessed by the Limulus amebocyte lysate (LAL) assay. l-arginine (l-Arg) transporter function was assessed in peripheral blood mononuclear cells (PBMCs). Plasma levels of urotensin II (UII) and tumour necrosis factor were measured before and after therapy. Sixteen subjects with clinically significant portal hypertension (16.5+/-1.1 mmHg) completed the study. Norfloxacin therapy was not superior to placebo in reducing HVPG (13.8+/-1.0 mmHg vs 13.6+/-1.2 mmHg, P=0.3). Furthermore, no alteration in l-Arg transport was detected after 4 weeks of norfloxacin therapy. Plasma UII levels correlated positively with HVPG (P=0.01) and the Child-Pugh score (P<0.05). However, UII levels following therapy did not parallel HVPG changes. Norfloxacin is not superior to placebo in reducing HVPG in subjects with clinically significant portal hypertension. Furthermore, norfloxacin does not appear to modulate the l-Arg transporter mechanism in this patient population. Although plasma UII correlates positively with HVPG, UII does not appear to have a direct role in modulating HVPG.
Tamashiro, H.; Arakaki, M.; Akagi, H.; Hirayama, K.; Smolensky, M.H.
Information is scant on both environmental and individual factors as potentiators of methylmercury (MeHg) toxicity in human beings and other animal species. Hypertension is quite common among the inhabitants of MeHg-polluted areas. It is of special interest to learn what is the health consequence among the hypertensives who have been exposed to MeHg for a prolonged period of time. This study was designed to delineate the toxicity of MeHg in animals having high blood pressure using the laboratory model of spontaneously hypertensive rats (SHR). This paper presents the mortality as well as distribution of mercury in the tissues of SHR and control rats treated orally with methylmercury chloride for 10 consecutive days.
Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina
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
Khodayar-Pardo, Parisá; Peña Aldea, Andrés; Ramírez González, Ana; Meseguer Carrascosa, Adela; Calabuig Bayo, Cristina
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.
Marques, Camila; Licks, Francielli; Zattoni, Ingrid; Borges, Beatriz; de Souza, Luiz Eduardo Rizzo; Marroni, Claudio Augusto; Marroni, Norma Possa
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
Background Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers. Methods We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54 years (range 38–73), median hepatic venous pressure gradient 18 mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58 years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs. Results The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00 m/hour, range 0.46–1.88) (p = 0.03). Likewise, the magnet travelled significantly longer in both fast (p = 0.04) and slow movements (p = 0.05) in the patient group. There was no significant difference in either gastric emptying time—23 minutes (range 5–131) in patients and 29 minutes (range 10.5–182) in healthy controls (p = 0.43)—or total gastrointestinal transit time—1.6 days (range 0.5–2.9) in patients and 2.0 days (range 1.0–3.9) in healthy controls (p = 0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine. Conclusion Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies. PMID:23216853
Kojima, Seiichiro; Ito, Hiroyuki; Takashimizu, Shinji; Ichikawa, Hitoshi; Matsumoto, Tomohiro; Hasebe, Terumitsu
A 64-year-old woman treated for anemia and ascites exhibited hepatic encephalopathy. Abdominal ultrasonography and computed tomography (CT) showed communication between the portal vein and the middle hepatic vein, indicating an intrahepatic portosystemic venous shunt (PSS). Since hepatic encephalopathy of the patient was resistant to medical treatment, interventional radiology was performed for the treatment of shunt obliteration. Hepatic venography showed anastomosis between the hepatic vein branches, supporting the diagnosis of idiopathic portal hypertension (IPH). To minimize the increase in portal vein pressure after shunt obliteration, partial splenic artery embolization (PSE) was first performed to reduce portal vein blood flow. Transileocolic venous obliteration (TIO) was then performed, and intrahepatic PSS was successfully obliterated using coils with n-butyl-2-cyanoacrylate (NBCA). In the present case, hepatic encephalopathy due to intrahepatic PSS in the patient with IPH was successfully treated by combination therapy using PSE and TIO. PMID:27651930
Takayasu, K.; Moriyama, N.; Suzuki, M.; Yamada, T.; Fukutake, T.; Shima, Y.; Kobayashi, C.; Musha, H.; Okuda, K.
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.
Zhu, Zhiming; Zhu, Shanjun; Zhu, Jijun; van der Giet, Markus; Tepel, Martin
Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion of acetylcholine significantly lowered mean arterial BP in control rats by 48 +/- 2% and by 32 +/- 1% in cold-induced hypertensive rats. The acetylcholine-induced reduction of mean arterial BP was significantly attenuated in cold-induced hypertensive rats (control rats, 45 +/- 2 mm Hg; cold-induced hypertensive rats, 34 +/- 3 mm Hg; P < .05). Administration of N(G)-nitro-L-arginine-methyl ester for 1 week significantly increased BP in control rats, whereas no effect could be observed in cold-induced hypertensive rats. In cold-induced hypertensive rats eNOS in aortic vessels was significantly reduced compared to control rats. In this nongenetic, nonsurgical animal model of cold-induced hypertensive rats an endothelial dysfunction can be observed due to reduced eNOS.
Arora, Ankur; Rajesh, S; Meenakshi, Yamini S; Sureka, Binit; Bansal, Kalpana; Sarin, Shiv Kumar
The purpose of this article is to describe the various portosystemic collateral pathways pertinent to portal hypertension on multi-detector row computed tomography (MDCT) and their clinical relevance, with special emphasis on the uncommon ones. The knowledge and understanding of the various patterns of portosystemic collateral channels has important implications both for the clinician and the interventionist. MDCT with its advanced post processing capabilities can exquisitely demonstrate these vascular pathways to help in therapeutic decision making. Teaching points • Portosystemic collaterals are an important cause of bleeding and hepatic encephalopathy. • Radiologists should be familiar with the imaging findings to effectively identify them. • Pre-operative knowledge of portosystemic collaterals is essential to avoid inadvertent vascular injury.
Philips, Cyriac; Paramaguru, Rajaguru; Kumar, Lijesh; Shenoy, Padmanabha; Augustine, Philip
Nodular regenerative hyperplasia (NRH) is a rare liver condition in which widespread benign transformation of the hepatic parenchyma into small regenerative nodules occur, leading to development of non-cirrhotic portal hypertension. Conditions associated with NRH include rheumatologic, hematological, autoimmune, infectious, neoplastic, or drug-related etiology. Accurate diagnosis is made on liver biopsy, showing diffuse micronodular transformation in the absence of fibrosis. Here, we present the second case in world literature of a middle-aged man presenting with recent onset sleep reversal and memory loss with darkening of skin for four years associated with systemic manifestations, in whom porto-systemic shunt syndrome due to NRH secondary to Behcet's disease was eventually diagnosed.
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
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
Wani, Zeeshan Ahmad; Mohapatra, Sonmoon; Khan, Afaq Ahmad; Mohapatra, Ashutosh; Yatoo, Ghulam Nabi
AIM To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODS One hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient (HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day (increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo. RESULTS A total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and non-responders respectively (P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients (42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients (80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects. CONCLUSION Addition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension. PMID:28261384
Ahn, Sun Young; Park, Soo Young; Tak, Won Young; Lee, Yu Rim; Kang, Eun Jeong; Park, Jung Gil; Lee, Won Kee; Lee, Kwan; Kweon, Young Oh
New definitions and criteria were released at the Baveno V consensus meeting. The purposes of this study were to verify Baveno V definitions and criteria for failure to control bleeding and to determine the usefulness of the combined use of the Adjusted Blood Requirement Index [ABRI: (number of blood units)/(final hematocrit-initial hematocrit)+0.01] with Baveno V criteria. In all, 246 consecutive liver cirrhosis patients with acute bleeding associated with portal hypertension were enrolled prospectively between January 2010 and October 2012. The treatment outcome on day 5 was assessed by endoscopy. For the ABRI calculation, two hematocrit levels were used as the initial hematocrit: the first level measured upon patient arrival (ABRI-A) and the lowest level measured before transfusion (ABRI-B). Treatment failures were identified in 53 patients, of whom 24 died. Based on repeated endoscopic findings, 29 patients were identified as treatment failures, while according to Baveno V criteria, 47 patients were regarded as treatment failures. The area under the receiver operating characteristic curve (AUROC) of Baveno V criteria was 0.906, and the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.0%, 98.4%, 93.6%, 95.5%, 53.41, and 0.17, respectively. The AUROC of Baveno V criteria was significantly greater than those of Baveno IV (P=0.0001) and Baveno II/III (P<0.0001) criteria. Adding ABRI-A or -B to Baveno V criteria resulted in a significant reduction of the AUROC (P<0.05). The Baveno V criteria are good predictors of treatment failure of early-stage acute gastrointestinal bleeding in patients with portal hypertension, while the addition of ARBI does not improve the prediction accuracy of the outcome of bleeding. © 2014 by the American Association for the Study of Liver Diseases.
Rodríguez, Sarai; Raurell, Imma; Torres-Arauz, Manuel; García-Lezana, Teresa; Genescà, Joan; Martell, María
Statins present many beneficial effects in chronic liver disease, but concerns about safety exist. We evaluated the hepatic effects of a nitric oxide-releasing atorvastatin (NCX 6560) compared to conventional statins. Simvastatin, atorvastatin and NCX 6560 were evaluated in four-week bile duct-ligated rats (BDL) simulating decompensated cirrhosis and in thirteen-week carbon tetrachloride (CCl4) intoxicated rats, a model of early cirrhosis. In the BDL model, simvastatin treated rats showed high mortality and the remaining animals presented muscular and hepatic toxicity. At equivalent doses, NCX 6560 eliminated hepatic toxicity and reduced muscular toxicity (60–74%) caused by atorvastatin in the more advanced BDL model; toxicity was minimal in the CCl4 model. Atorvastatin and NCX 6560 similarly reduced portal pressure without changing systemic hemodynamics in both models. Atorvastatin and NCX 6560 caused a mild decrease in liver fibrosis and inflammation and a significant increase in intrahepatic cyclic guanosine monophosphate. NCX 6560 induced a higher intrahepatic vasoprotective profile (activated endothelial nitric oxide synthase and decreased platelet/endothelial cell adhesion molecule-1), especially in the CCl4 model, suggesting a higher benefit in early cirrhosis. In conclusion, NCX 6560 improves the liver profile and portal hypertension of cirrhotic rats similarly to conventional statins, but with a much better safety profile. PMID:28084470
Rosa, Mariana Nogueira de Paula; Hessel, Gabriel; Alves De Tommaso, Adriana María
In Brazil, approximately 130 new cases of hepatitis A per 100,000 inhabitants occur annually and 15% of the population has been in contact with hepatitis B virus. Portal hypertension causes hypersplenism and reduces T cell production, which may lead to less effective response to hepatitis vaccination. The objective of the study was to evaluate the response to hepatitis A and B vaccination in patients with portal hypertension secondary to chronic liver disease or portal vein thrombosis. Twenty-three patients (2 to 18 years) with portal hypertension seen at the Pediatric Hepatology Service of Hospital das Clínicas, Universidade Estadual de Campinas, between 1994 and 2006 were studied. Hepatitis A and B serology was tested in all patients. Patients who had not been vaccinated before their visits received the vaccines during the study period. Patients who had been vaccinated before but had negative anti-HB antibodies received a booster dose, and their serology was repeated Blood counts were performed in each patient to assess for immunosuppression. Eighteen patients received hepatitis A vaccine and all became positive for anti-HAV antibodies. All patients had received hepatitis B vaccine and 17 (73.9%) were anti-HBs positive at the time of the study The other 6 received a booster dose and became anti-HBs positive afterward. The anti-HBs-positive and -negative patients did not differ significantly in age, leukocytes, lymphocytes, or duration between the vaccination and positive serology. In this study, hepatitis A vaccines elicited a 100% response and hepatitis B vaccine conferred protection and induced an anamnestic response in pediatric patients with portal hypertension.
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
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
Pal, Atanu; Rhoads, David B.; Tavakkoli, Ali
Background The global epidemic of Type-2-Diabetes (T2D) highlights the need for novel therapeutic targets and agents. Roux-en-Y-Gastric-Bypass (RYGB) is the most effective treatment. Studies investigating the mechanisms of RYGB suggest a role for post-operative changes in portal glucose levels. We investigate the impact of stimulating portal glucose sensors on systemic glucose levels in health and T2D, and evaluated the role of sodium-glucose-cotransporter-3 (SGLT3) as the possible sensor. Methods Systemic glucose and hormone responses to portal stimulation were measured. In Sprague-Dawley (SD) rats, post-prandial state was simulated by infusing glucose into the portal vein. The SGLT3 agonist, alpha-methyl-glucopyranoside (αMG), was then added to further stimulate the portal sensor. To elucidate the neural pathway, vagotomy or portal denervation was followed by αMG+glucose co-infusion. The therapeutic potential of portal glucose sensor stimulation was investigated by αMG-only infusion (vs. saline) in SD and Zucker-Diabetic-Fatty (ZDF) rats. Hepatic mRNA expression was also measured. Results αMG+glucose co-infusion reduced peak systemic glucose (vs. glucose alone), and lowered hepatic G6Pase expression. Portal denervation, but not vagotomy, abolished this effect. αMG-only infusion lowered systemic glucose levels. This glucose-lowering effect was more pronounced in ZDF rats, where portal αMG infusion increased insulin, C-peptide and GIP levels compared to saline infusions. Conclusions The portal vein is capable of sensing its glucose levels, and responds by altering hepatic glucose handling. The enhanced effect in T2D, mediated through increased GIP and insulin, highlights a therapeutic target that could be amenable to pharmacological modulation or minimally-invasive surgery. PMID:27806092
Idrissi, Mounia Lakhdar; Babakhoya, Abdeladim; Hida, Moustapha
Introduction L'hypertension portale n'est pas exceptionnelle chez l'enfant. L'hémorragie digestive en est une complication redoutable pouvant mettre en jeu le pronostic vital. Cette hémorragie, pouvant être isolée, confie à l'examen endoscopique un intérêt diagnostique majeur. L'endoscopie digestive haute a également un intérêt pronostique et thérapeutique incontournable. L'objectif de ce travail était d'analyser les aspects endoscopiques de l'hypertension portale, faire une corrélation entre ces aspects et le risque hémorragique éventuel et mettre en évidence le rôle de l'endoscopie dans le traitement et la surveillance. Méthodes Notre étude est une analyse rétrospective de 135 endoscopies digestives hautes effectuées chez 68 enfants atteints d'hypertension portale sur une période de 8 ans. Résultats L'endoscopie a permis de mettre en évidence les varices œsogastriques dans 55 cas (80.9%). Elle était le premier moyen diagnostique de l'hypertension portale chez 5 patients ayant présenté une hémorragie digestive isolée. Elle a permet aussi d'apprécier le risque hémorragique qui est étroitement lié au stade des varices œsophagiennes et à la présence des varices tubérositaires. Neuf enfants ont bénéficié de la ligature élastique des varices œsophagiennes avec un taux de succès de 89%. Conclusion L'oesogastroscopie recherchant et traitant les varices œsogastriques est indispensable dans les hypertensions portales de l'enfant. Inversement, nous soulignons son intérêt majeur en matière diagnostique de l'hémorragie digestive isolée de l'enfant ou la découverte de varices pose à posteriori le diagnostic de l'hypertension portale. PMID:22937191
Sabbatini, M; Strocchi, P; Vitaioli, L; Amenta, F
The influence of hypertension on the morphology of hippocampus was assessed in spontaneously hypertensive rats of two, four and six months and in age-matched normotensive Wistar-Kyoto rats. Values of systolic pressure were slightly increased in two-month-old spontaneously hypertensive rats in comparison with age-matched Wistar-Kyoto rats and augmented progressively with age in spontaneously hypertensive rats. No microanatomical changes were observed in the hippocampus of spontaneously hypertensive rats of two months in comparison with age-matched Wistar-Kyoto rats, whereas a decrease of white matter volume was observed in the CA(1) subfield and in the dentate gyrus of four-month-old spontaneously hypertensive rats. In the hippocampus of six-month-old spontaneously hypertensive rats a reduction of grey matter volume both in the CA(1) subfield and in the dentate gyrus, a loss of neurons affecting to a greater extent the CA(1) subfield and an increase of glial fibrillary acid protein-immunoreactive astrocytes was found. The occurrence of apoptosis and/or necrosis identified using the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick end labelling technique was also observed in the CA(1) subfield and to a lesser extent in the dentate gyrus. The only change noticeable in the CA(3) subfield of six-month-old spontaneously hypertensive rats was a slight increase in the number of glial fibrillary acid protein-immunoreactive astrocytes. These findings indicate the occurrence of neuronal loss and of astrocyte changes in the hippocampus of spontaneously hypertensive rats of six months, being the CA(1) subfield the area most affected. The relevance of these neurodegenerative changes in hypertension and the possible occurrence of apoptosis and/or necrosis as expression of hypertensive brain damage is discussed.
Blanchard, H; Beauchamps, G; Normandin, D; Montupet, P; Bensoussan, A L
From 1960 to 1981, 31 children, 18 boys and 13 girls, have been treated at Ste-Justine Hospital for extra-hepatic portal hypertension. Age at the onset of gastro-intestinal bleeding 3 1/2 months and 13 years. Splenomegaly with hypersplenism, hematemesis and melena have been the most frequent clinical manifestations. Percutaneous splenoportography be coelio-mesenteric arteriography confirmed the diagnosis of cavernomatous transformation of the portal vein. Among the 31 children, 28 bled from their varices, the 3 others did not to date. Among the 28 patients with active bleeding complication, 7 have been treated conservatively, 11 had sclerotherapy (sclerosing injections of varices). On the surgical point of view, 7 had ligation of varices with intra-thoracic transposition of the spleen in 5 of them. Portosystemic shunts were performed in 10 patients, 3 central spleno-renal and 7 cavo-mesenteric shunt. Each of these 28 patients had an average of 9,5 episodes of gastro-intestinal bleeding, 8.7 hospitalizations, and received 7.5 liter of blood. Medical treatment, sclerotherapy, ligature of varices and intra-thoracic transposition of the spleen are palliative measures. Nevertheless the procedures are time and life savers, allowing improvement and development of natural porto-systemic shunts. Follow up of unshunted patients on a period of 8 to 17 years revealed a decreasing frequency and intensity of the hemorrhagic manifestations. Operative risks and morbidity of recurrent bleeding should be the guidelines for surgery. Natural course of illness and possible neuro-psychiatric consequences of a porto-caval shunt should also be considered.
Sohn, Joo Hyun; Kim, Yongsoo; Kim, Jinoo
Objective To investigate the role of contrast-enhanced ultrasonography (CEUS) and Doppler ultrasonography (DUS) in the diagnosis of severe portal hypertension (PH) in patients with liver cirrhosis (LC). Methods Patients with PH scheduled to receive hepatic venous pressure gradient (HVPG) measurement were recruited for this study. Hepatic DUS and CEUS were performed successively. Several Doppler and CEUS parameters were explored for correlation with HVPG values and their association with severe PH (≥ 12 mmHg of HVPG). Comparison of the parameters between the severe and non-severe PH groups and their correlation with HVPG values was evaluated. A receiver operating characteristic (ROC) curve analysis was also performed to investigate the performance in order to diagnose severe PH. Results Fifty-three consecutive patients were enrolled in this study. Among them, 43 patients did not have significant ascites. Compared with the non-severe PH group, portal venous velocity and intrahepatic transit time (ITT) were significantly reduced in the severe PH group (all p<0.05). Difference between inspiratory and expiratory hepatic venous damping indices (ΔHVDI), hepatic venous arrival time (HVAT) and ITT moderately correlated with HVPG (r = -0.358, -0.338, and -0.613, respectively). Areas under the curves for severe PH were 0.94 of ITT and 0.72 of HVAT, respectively (all p<0.05). ITT under 6 seconds indicated severe PH with a sensitivity of 92% and a specificity of 89%. Conclusions Hepatic CEUS may be more useful in estimating the HVPG value and determining the presence of severe PH compared to DUS, and ITT was the most accurate parameter to diagnose severe PH. PMID:25798930
Trebicka, Jonel; Krag, Aleksander; Gansweid, Stefan; Schiedermaier, Peter; Strunk, Holger M.; Fimmers, Rolf; Strassburg, Christian P.; Bendtsen, Fleming; Møller, Søren; Sauerbruch, Tilman; Spengler, Ulrich
Background TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS. Methods Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics. Results Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not. Conclusion Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension. PMID:24386183
Bennek, J; Tröbs, R B; Mühlig, K; Richter, T
Between 1977 and 1995, 19 children with portal hypertension (nine extrahepatic, ten intrahepatic) were treated by transpositioning the spleen into the left abdominal wall. Among the patients with intrahepatic portal hypertension three died. Two patients underwent secondary diminuition of the transposed spleen due to relapsed hypersplenism. In one of our first patients the transposed spleen atrophied after tangential resection. All surviving patients except one preserved hepatic function. The serum colloid osmotic pressure was stable. Plasma ammonia levels were normal. Serum immunoglobulins (IgG, IgM, IgA and IgG subclasses) and complement components (C3c, C4) were analyzed. After transposition patients had normal or slightly elevated values of these proteins compared with controls.
Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma; Achebe, Jennifer; Odenigbo, Charles; Oguejiofor, Fidelis
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
Staubli, Sergej E. L.; Gramann, Tobias; Schwab, Christoph; Semela, David; Hechelhammer, Lukas; Engeler, Daniel S.; Abt, Dominik; Mordasini, Livio
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
Wiese, Signe; Timm, Annette; Nielsen, Lars B; Goetze, Jens P; Bendtsen, Flemming; Møller, Søren
Activated hepatic stellate cells synthesize the matrix metalloprotease ADAMTS13, which may be involved in the development of liver cirrhosis and portal hypertension. Plasma ADAMTS13 activity has been reported as both increased and decreased in cirrhosis, but ADAMTS13 protein has not previously been examined. To evaluate ADAMTS13 protein in the hepatic circulation and the relation to disease severity, portal pressure, and systemic hemodynamics in cirrhotic patients. Sixty-one cirrhotic patients (Child class: A=22; B=21; C=18) and nine healthy controls underwent a liver vein catheterization with measurement of splanchnic and systemic hemodynamics, and plasma ADAMTS13 protein concentration in a hepatic vein and the femoral artery. ADAMTS13 protein concentrations were increased in cirrhotic patients compared with controls (774ng/ml [IQR: 585-955] vs. 538ng/ml [IQR: 484-631], p<0.03). There were no significant correlations to MELD score, Child Pugh score, portal pressure, nor systemic vascular resistance or cardiac output. The increased concentration of ADAMTS13 protein in the hepatic circulation may reflect an increased number of active hepatic stellate cells in cirrhosis. However, ADAMTS13 was unrelated to portal hypertension and systemic hemodynamics. In conclusion, ADAMTS13 does not appear to be associated to disease severity or the hemodynamic derangement in patients with cirrhosis. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Savić, Zeljka; Vracarić, Vladimir; Hadnadjev, Ljiljana; Petrović, Zora; Damjanov, Dragomir
Portal hypertension (PH) is hemodynamical abnormality associated with the most serious complications of alcoholic liver cirrhosis (ALC): ascites, varices and variceal bleeding. The aim of this study was to determine characteristics of portal hypertension, especially of upper gastrointestinal bleedings in patients with alcoholic liver cirrhosis (ALC). A total of 237 patients with ALC were observed in a 3-year period. A total of 161 patients (68%) were hospitalized because of PH elements: 86 (36.3%) had upper gastrointestinal bleeding, 75 (31.7%) were decompensated. Only 76 (32%) of the patients had icterus. General mortality was 85 (36%). According to the source of bleeding, 61 (71%) patients bled from varices, and 25 (29%) from other sources with existing varices but non-incriminated for bleeding in 16 (64%) of those patients. Active bleeding or stigmata of recent bleeding were found in 63 (73%) cases. Endoscopic treatment of variceal bleeding along with octreotide applied in 20 (32.78%) patients, just octreotide in 32 (52.46%), and octreotid plus balloon tamponade in 9 (14.75%). According to Child-Pugh classification, 25 (29%) of the bleeding patients were in class A, score 5.4; 43 (50%) in class B, score 7.8; and 18 (21%) in class C, score 10.9. Average hemoglobin level was 93 g/L, hematocrit 0.27, AST 71.52 U/L (normal to 37 U/L), ALT 37.74 U/L (normal to 40 U/L). Until this bleeding episode, 41 (47%) of the patients already bled. In the decompensated patients 3 (4%) were in Child Pugh class A, score 6; 42 (56%) in class B, score 8.3; and 30 (40%) in class C, score 10.6. Until this decompensation episode, 7 (9.3%) patients already bled. Patients with ALC need early detection of varices, primary and secondary profilaxis of variceal bleeding and adequate therapy of ascites. When bleeding occurs, patients need urgent upper endoscopy and intensive treatment.
Piasecki, C; Chin, J; Greenslade, L; McIntyre, N; Burroughs, A K; McCormick, P A
Changes in mucosal blood flow may be important in the pathogenesis of many conditions. Study of mucosal blood perfusion is difficult, and available methods have significant technical limitations. This study describes the development of an instrument for endoscopy, which indicates blood flow indirectly, by measuring the quantity of tissue oxygen that can diffuse from the mucosa to a luminal surface electrode. The instrument was used through an endoscope in patients with portal hypertension (n = 14), scleroderma (n = 3), disease controls (n = 7), and normal controls (n = 11). In portal hypertension readings were one quarter that in normal controls in both antrum (geometric mean (SEM) 35 (1.1)), nanoamps v 137 (1.1), and upper corpus 34 (1.1) v 125 (1.1)). Scleroderma patients showed greatly reduced oxygen readings in both antrum (18 (1.2)) and corpus (24 (1.2)), an expected but hitherto undiscovered result. These differences are highly significant (p = 0.0001), and the findings suggest that tissue hypoxia may contribute to mucosal changes in portal hypertensive gastropathy and in scleroderma. PMID:7797112
Maruyama, Hitoshi; Kondo, Takayuki; Sekimoto, Tadashi; Yokosuka, Osamu
Abstract Cirrhosis and idiopathic portal hypertension (IPH) are 2 major diseases showing portal hypertension. However, characteristics and outcomes of IPH with ascites have not yet been determined. The aim of the study was to examine the influence of ascites on the long-term clinical course of IPH. This observational study compared the long-term clinical findings including portal hemodynamics demonstrated by Doppler ultrasonography between 166 cirrhosis (87 males and 79 females; mean age ± standard deviation, 62.5 ± 11.8 years; age range, 20–89 years) and 14 IPH patients (3 males and 11 females; mean age ± standard deviation, 64.2 ± 6.6 years; age range, 51–78 years). Both groups comprised of consecutive patients from November 2007 through February 2013 and were studied retrospectively. The median observation period was 33.4 months for ascites and 34.5 months for survival. Ascites was detected in 60/166 (36.1%) and 116/166 (69.9%) cirrhosis patients and in 7/14 (50%) and 9/14 (64.3%) IPH patients, at baseline and at the end of the observation period, respectively. The cumulative incidence of ascites was 12.3% at 1 year, 35.9% at 3 years, and 59.9% at 5 years in cirrhosis, and 25% at 3 years, and 50% at 5 years in IPH (P = 0.36). Deterioration of ascites in patients showing mild ascites at baseline was found in 32.4% of cirrhosis patients and 42.9% of IPH patients (P = 0.41). Serum creatinine (mg/dl) at baseline was significantly higher in IPH patients who developed ascites (n = 2, 0.74 ± 0.14) than in those who did not (n = 5, 0.526 ± 0.06, P = 0.029). The overall survival rate appeared to favor IPH (100% at 1 year, 92.9% at 3 and 5 years; P = 0.2) more than cirrhosis (87.7% at 1 year, 75.2% at 3 years, and 63.6% at 5 years), but did not reach statistical significance. However, in patients with ascites at baseline, the survival rate was significantly better in IPH (100% at 1, 3, and 5 years, P = 0
Tokai, Koichi; Miyatani, Hiroyuki; Yoshida, Yukio; Yamada, Shigeki
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
Møller, Søren; Henriksen, Jens H; Bendtsen, Flemming
In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. As a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs, antibiotics, drugs with specific effects on fibrogenesis and inflammation, and drugs that target specific receptors.
Pomier-Layrargues, Gilles; Bouchard, Louis; Lafortune, Michel; Bissonnette, Julien; Guérette, Dave; Perreault, Pierre
The transjugular intrahepatic portosystemic shunt (TIPS) represents a major advance in the treatment of complications of portal hypertension. Technical improvements and increased experience over the past 24 years led to improved clinical results and a better definition of the indications for TIPS. Randomized clinical trials indicate that the TIPS procedure is not a first-line therapy for variceal bleeding, but can be used when medical treatment fails, both in the acute situation or to prevent variceal rebleeding. The role of TIPS to treat refractory ascites is probably more justified to improve the quality of life rather than to improve survival, except for patients with preserved liver function. It can be helpful for hepatic hydrothorax and can reverse hepatorenal syndrome in selected cases. It is a good treatment for Budd Chiari syndrome uncontrollable by medical treatment. Careful selection of patients is mandatory before TIPS, and clinical followup is essential to detect and treat complications that may result from TIPS stenosis (which can be prevented by using covered stents) and chronic encephalopathy (which may in severe cases justify reduction or occlusion of the shunt). A multidisciplinary approach, including the resources for liver transplantation, is always required to treat these patients. PMID:22888442
Philips, Cyriac Abby; Anand, Lovkesh; Kumar, K N Chandan; Kasana, Vivek; Arora, Ankur
We present a rare case of spontaneous trans-splenic shunt and intra-splenic collaterals in a patient with liver cirrhosis and portal hypertension. The shunt and presence of cirrhosis and portal hypertension was incidentally detected by abdominal computed tomographic imaging during evaluation for abdominal pain. There has been a single report on the presence of trans-splenic shunt in two children with extra-hepatic portal venous obstruction but no cases that report intra-splenic collaterals: to the best of our knowledge, this is the first reported case of spontaneous trans-splenic shunt in the presence of intra-splenic collaterals and incidental multiple splenic artery aneurysms that developed in an adult with compensated cirrhosis and portal hypertension.
Gyoten, Kazuyuki; Mizuno, Shugo; Kato, Hiroyuki; Murata, Yasuhiro; Tanemura, Akihiro; Azumi, Yoshinori; Kuriyama, Naohisa; Kishiwada, Masashi; Usui, Masanobu; Sakurai, Hiroyuki; Isaji, Shuji
Background In adult living donor liver transplantation (ALDLT), graft-to-recipient weight ratio of less than 0.8 is incomplete for predicting portal hypertension (>20 mm Hg) after reperfusion. We aimed to identify preoperative factors contributing to portal venous pressure (PVP) after reperfusion and to predict portal hypertension, focusing on spleen volume-to-graft volume ratio (SVGVR). Methods In 73 recipients with ALDLT between 2002 and 2013, first we analyzed survival according to PVP of 20 mm Hg as the threshold, evaluating the efficacy of splenectomy. Second, we evaluated various preoperative factors contributing to portal hypertension after reperfusion. Results All of the recipients with PVP greater than 20 mm Hg (n = 19) underwent PVP modulation by splenectomy, and their overall survival was favorable compared with 54 recipients who did not need splenectomy (PVP ≤ 20 mm Hg). Graft-to-recipient weight ratio had no correlation with PVP. Multivariate analysis revealed that estimated graft and spleen volume were significant factors contributing to PVP after reperfusion (P < 0.0001 and P < 0.0001, respectively). Furthermore, estimated SVGVR showed a significant negative correlation to PVP after reperfusion (R = 0.652), and the best cutoff value for portal hypertension was 0.95. Conclusions In ALDLT, preoperative assessment of SVGVR is a good predictor of portal hypertension after reperfusion can be used to indicate the need for splenectomy before reperfusion. PMID:27472097
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; Diehl, Anna Mae
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.
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
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
Hong, Defei; Cheng, Jian; Wang, Zhifei; Shen, Guoliang; Xie, Zhijie; Wu, Weiding; Zhang, Yuhua; Zhang, Yuanbiao; Liu, Xiaolong
Our research was conducted to analyze the outcomes of two laparoscopic splenectomy plus pericardial devascularization (LSPD) techniques in the management of portal hypertension (PTH) and hypersplenism. Between May 2012 and May 2013, 41 patients with PTH and hypersplenism undergoing LSPD were retrospectively analyzed. Of them, 29 patients received LSPD by LigaSure Vessel Sealing System (LVSS) and Endo-GIA universal endoscopic vascular linear staplers (Endo-GIA) (EG Group) and 12 patients received LSPD by LVSS and Hem-o-Lock (HL Group). Operating time, intraoperative blood loss, postoperative course, and hospitalization costs were compared between the two LSPD combination techniques. There were no significant differences in preoperative patient characteristics of the two groups. Significantly less operating time, intraoperative blood loss, and postoperative complications were observed in EG Group. The incidence of portal vein thrombosis was lower in the EG Group (3.4 vs. 8.3%), as well as the incidence of pancreatic fistula (0 vs. 8.3%). Upper gastrointestinal hemorrhage was not observed in either group. Uncontrolled bleeding warranted conversion to open surgery in one case in EG Group (conversion rate 3.4%) and in two cases in HL Group (conversion rate 16.7%). Two patients (16.7%) in HL Group underwent successful emergency exploratory laparotomy due to uncontrolled intraabdominal bleeding postoperatively. No re-operation was needed in EG Group. Two patients experienced liver failure after surgery in each group. Of those, three patients were managed successfully and one patient refused further therapy. While the overall complication rate was significantly lower in EG Group (17.2 vs. 58.3%, P < 0.05), overall hospitalization costs remained significantly higher for EG Group. The results suggest that the modified Endo-GIA and LVSS technique is a safe and effective combination approach to LSPD with shorter operative time, less intraoperative blood loss, lower conversion
Anderson, R J; Cronin, R E; McDonald, K M; Schrier, R W
Clinical states with portal venous hypertension are frequently associated with impairment in renal hemodynamics and water excretion, as well as increased renin secretion. In the present investigation, portal venous pressure (PVP) was increased in anesthetized dogs undergoing a water diuresis. Renal arterial pressure was maintained constant in all studies. As PVP was increased from 6 to 20 mm Hg, decreases in cardiac output (2.5-2.0 liter/min, P less than 0.05) and mean arterial pressure (140-131 mm Hg, P less than 0.05) were observed. Increases in PVP were also associated with decreases in glomerular filtration rate (GFR, 40-31 ml/min, P less than 0.001), renal blood flow (RBF, 276-193 ml/min, P less than 0.001), and increases in renin secretion (232-939 U/min, P less than 0.025) in innervated kidneys. No significant change in either GFR or RBF and a decrease in renin secretion occurred with increases in PVP in denervated kidneys. To dissociate the changes in cardiac output and mean arterial pressure induced by increase PVP from the observed decreases in GFR and RBF, studies were performed on animals undergoing constriction of the thoracic inferior vena cava. In these studies, similar decreases in cardiac output and mean arterial pressure were not associated with significant changes in GFR or RBF. Increases in PVP also were associated with an antidiuresis as urine osmolality increased from 101 to 446 mosmol/kg H2O (P less than 0.001). This antidiuresis was significantly blunted but not abolished by acute hypophysectomy. In hypophysectomized animals, changes in free water clearance and urine flow were linearly correlated as PVP was increased. These studies indicate that increases in PVP result in decreases in GFR and RBF and increases in renin secretion mediated by increased renal adrenergic tone. Increased PVP is also associated with antidiuresis; this antidiuresis is mediated both by vasopressin release and by diminished tubular fluid delivery to the distal
Qi, Xing-Shun; Bai, Ming; Yang, Zhi-Ping; Fan, Dai-Ming
Nowadays, transjugular intrahepatic portosystemic shunt (TIPS) has become a mainstay treatment option for the management of portal hypertension-related complications in liver cirrhosis. Accumulated evidence has shown that its indications are being gradually expanded. Notwithstanding, less attention has been paid for the selection of an appropriate stent during a TIPS procedure. Herein, we attempt to review the current evidence regarding the diameter, type, brand, and position of TIPS stents. Several following recommendations may be considered in the clinical practice: (1) a 10-mm stent may be more effective than an 8-mm stent for the management of portal hypertension, and may be superior to a 12-mm stent for the improvement of survival and shunt patency; (2) covered stents are superior to bare stents for reducing the development of shunt dysfunction; (3) if available, Viatorr stent-grafts may be recommended due to a higher rate of shunt patency; and (4) the placement of a TIPS stent in the left portal vein branch may be more reasonable for decreasing the development of hepatic encephalopathy. However, given relatively low quality of evidence, prospective well-designed studies should be warranted to further confirm these recommendations. PMID:24914368
Heimgartner, Benjamin; Dawson, Heather; De Gottardi, Andrea; Wiest, Reiner; Niess, Jan Hendrik
Small intestinal bleeding in Crohn's disease patients with noncirrhotic portal hypertension and partial portal and superior mesenteric vein thrombosis is a life-threatening event. Here, a case is reported in which treatment with azathioprine may have resulted in nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis. The 56-year-old patient with Crohn's disease developed nodular regenerative hyperplasia under treatment with azathioprine. He was admitted with severe bleeding. Gastroscopy showed small esophageal varices without bleeding stigmata. Blood was detected in the terminal ileum. CT scan revealed a partial portal vein thrombosis with extension to the superior mesenteric vein, thickening of the jejunal wall and splenomegaly. Because intestinal bleeding could not be controlled by conservative treatment, the thrombus was aspirated and a transjugular intrahepatic portosystemic shunt (TIPS) was placed. Switching the immunosuppressive medication to infliximab controlled Crohn's disease activity. Bleeding was stopped, hemoglobin normalized, and thrombocytopenia and bowel movements improved. In summary, small intestinal bleeding in a Crohn's patient with nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis can be efficiently treated by TIPS. TIPS placement together with infliximab treatment led to the improvement of the blood panel and remission in this patient.
Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B
Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG.
Luo, Xuefeng; Nie, Ling; Wang, Zhu; Tsauo, Jiaywei; Tang, Chengwei; Li, Xiao
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.
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
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
Herrera, M F; Hoyos, C; Prado, E; Orozco, H
With the aim of investigating the preoperative frequency of undernutrition and its impact on the infectious morbidity in patients without malignant disease, we studied prospectively 41 patients operated because of portal hypertension between 1987 and 1989 at the Instituto Nacional de la Nutrición. All patients were evaluated through anthropometric analysis and biochemical markers one week before the surgical procedure. A standard scheme of antibiotic profilaxis was used during surgery and the preoperative complications were registered up to discharge from the hospital. Undernutrition was considered when the serum albumin was less than 3 mg/dL or the total lymphocyte count was under 900, associated with a 10% weight loss in six months and reduction of one or more anthropometric parameters below the 30th percentile of the normal value. The group consisted of 17 males and 24 females with a mean age of 48 +/- 14 years old. 35 were Child A, four Child B and two Child C. Ten patients had a distal splenorenal shunt, seven esophageal devascularization and 24 gastric desvascularization with splenectomy. Twenty eight patients were well nourished and 13 undernourished. The two groups were comparable in all parameters except for the nutritional status. In the first group seven patients developed 10 complications and in the undernourished group eight patients had 14 complications (p less than 0.05 chi 2). There was no significant difference in the mortality rate. Infections occurred more frequently in: urinary tract, surgical wound, lung and pleura, and esophageal fistulae was an additional complication. The univariate analysis of the anthropometric parameters did not show significant differences between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Warwick, Anne B.; Kalapurakal, John A.; Ou, San-San; Green, Daniel M.; Norkool, Pat A.; Peterson, Susan M.; Breslow, Norman E.
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.
Fontana, Robert J.; Sanyal, Arun J.; Ghany, Marc G.; Bonkovsky, Herbert L.; Morgan, Timothy R.; Litman, Heather J.; Reid, Andrea E.; Lee, William M.; Naishadham, Deepa
OBJECTIVES To determine the incidence and risk factors associated with new onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC). METHODS 831 CHC patients with bridging fibrosis or cirrhosis at entry were prospectively monitored for clinical and histological liver disease progression while receiving either low dose peginterferonα2a or no antiviral therapy in the HALT-C Trial. Upper endoscopy with grading of PHG was performed at baseline and year 4 of the study. The presence and severity of PHG were determined using the NIEC criteria and worsening PHG was defined as a score increase of > 1 point. RESULTS During a median follow-up of 3.85 years, 50% of the 514 subjects without PHG developed new onset PHG while 26% of the 317 patients with baseline PHG had worsening PHG. Independent predictors of new onset PHG included higher alkaline phosphatase and being diabetic, while predictors of worsening PHG were Caucasian race, lower albumin, and higher serum AST/ ALT ratio and HOMA levels. New onset and worsening PHG were significantly associated with clinical as well as histological progression. New onset and worsening PHG were also associated with new onset and worsening of gastroesophageal varices. CONCLUSIONS New onset and worsening PHG develops at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors. PMID:21139575
Background Hepatic fibrosis is characterized by intense tissue remodeling, mainly driven by matrix metalloproteinases. We previously identified CO3-610, a type III collagen neoepitope generated by matrix metalloproteinase (MMP)-9, and tested its performance as a fibrosis marker in rats with bile-duct ligation. In this study, we assessed whether CO3-610 could be used as a surrogate biomarker of liver fibrosis and portal hypertension in carbon tetrachloride-induced experimental fibrosis. Results For this study, 68 Wistar rats were used. Serum CO3-610 was measured by ELISA. Liver fibrosis was quantified by Sirius red staining. Serum hyaluronic acid (HA) was measured with a binding-protein assay. Gene expression of collagens I and III, Mmp2 and Mmp9, and tissue inhibitors of matrix metalloproteinase 1 (Timp1) and 2(Timp2) was quantified by PCR. Hemodynamic measurements were taken in a subgroup of animals. A close direct relationship was found between serum CO3-610 and hepatic collagen content (r = 0.78; P < 0.001), superior to that found for serum HA (r = 0.49; P < 0.05). CO3-610 levels in rats with severe fibrosis (43.5 ± 3.3 ng/mL, P < 0.001) and cirrhosis (60.6 ± 4.3 ng/mL, P < 0.001) were significantly higher than those in control animals (26.6 ± 1.3 ng/mL). Importantly, a highly significant relationship was found between serum CO3-610 and portal hypertension (r = 0.84; P < 0.001). Liver Mmp9 expression increased significantly in fibrotic animals but decreased to control levels in cirrhotic ones. Conclusions Circulating CO3-610 behaves as a reliable indicator of hepatic remodeling and portal hypertension in experimental fibrosis. This peptide could ultimately be a useful marker for the management of liver disease in patients. PMID:21813019
Zemancíková, Anna; Török, Jozef
Hypertensive rats serve as valuable tools for studies of dysregulations in cardiovascular functions before and during pathological elevation of blood pressure. They exhibit many defects in structure and function of heart and vessels which are often related to severity of hypertension. The relationship of blood pressure level and manifestation of aberrations in selected cardiovascular and metabolic parameters were determined in 20-week-old normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and in their F1 offspring borderline hypertensive rats (BHR), and also in normotensive Wistar rats which are genetically less compatible with the other mentioned rat strains. Systolic blood pressure and heart rate were measured in conscious rats by the non-invasive tail-cuff method. At the end of the treatment, rats were sacrificed, relative weight of their left heart ventricle and liver were determined and plasma concentration of glucose and triglycerides were measured. Thoracic aorta and superior mesenteric artery were isolated and prepared for isometric tension recording. Neurogenic contractions were elicited by electrical stimulation of perivascular adrenergic nerves. The level of systolic blood pressure in WKY rats (106.0 ± 0.4 mmHg), BHR (149.5 ± 2.5 mmHg) and SHR (186.4 ± 3.9 mmHg) corresponded with the impairment of acetylcholine-induced relaxation of isolated thoracic aorta and with the increase in sensitivity of contractile responses to exogenous noradrenaline and to electrical stimulation of perivascular adrenergic nerves in mesenteric artery. However, rats of the normotensive strain Wistar (118.1 ± 2.0 mmHg) exhibited arterial contractions similar to those obtained in hypertensive rats. Wistar rats had also the highest relative liver weight and plasma triglyceride concentration. These observations indicate that when comparing non-related rat strains the higher magnitude of arterial contractions and abnormal lipid parameters may not
Pörsti, I; Arvola, P; Wuorela, H; Vapaatalo, H
The effects of increased dietary calcium on the development of hypertension and vascular smooth muscle responses were studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Both hypertensive and normotensive animals were divided into two groups; the calcium content of the normal diet was 1.1% and that of the high calcium diet 3.1%. During the 12-week study, calcium supplementation significantly attenuated the increase in systolic blood pressure in the hypertensive rats but did not affect blood pressure in the normotensive rats. The contractile responses of endothelium-denuded mesenteric arterial rings to potassium chloride were similar in all study groups. The contractions to norepinephrine were not altered by the high calcium diet either, but smooth muscle sensitivity to this agonist was lower in the normotensive than in the hypertensive rats. Potassium relaxation was used to evaluate the activity of vascular smooth muscle Na+,K(+)-ATPase. The maximal rate of potassium relaxation was fastest in the normotensive groups but was also clearly faster in calcium-treated hypertensive rats when compared with hypertensive rats on a normal diet. Platelets were used as a cell model for the analysis of intracellular free calcium concentration, which was measured by the fluorescent indicator quin-2. Intracellular free calcium was significantly reduced in the hypertensive rats by calcium supplementation and was not affected in the normotensive rats. In conclusion, a reduction of intracellular free calcium concentration indicating improved calcium regulation and a concomitant alteration in vascular relaxation probably reflecting increased activity of smooth muscle Na+,K(+)-ATPase may contribute to the blood pressure-lowering effect of a high calcium diet.
Schlüter, Klaus-Dieter; Schreckenberg, Rolf; da Costa Rebelo, Rui Manuel
The effect of exercise on the progression of hypertension and development of heart failure has been extensively studied in spontaneously hypertensive rats (SHRs), but results published thus far have not revealed a clear picture. Studies differ with respect to the age and sex of rats, duration of exercise and exercise protocols. This study was aimed to examine the influence of age at the start of exercise and the effect of the duration of exercise on blood pressure and hypertrophy, which has not been previously investigated. We identified 18 reports in the literature (with a total of about 410 rats) that investigated the effect of exercise on SHR. A reduction in blood pressure was observed in rats that started exercise protocols in the pre-hypertensive or very early hypertensive state, but not in older rats. Exercise lowered the heart weight-to-body weight ratio in rats starting exercise at a very early age, but not in rats at an advanced age. A reduction in blood pressure was observed in animals that had a short period of training, but the effect was lost when the duration of exercise was prolonged. Exercise reduced resting heart rates in all groups and increased the heart weight-to-body weight ratio in groups that were exposed to free running wheels, but not in rats that performed treadmill exercise. In conclusion, exercise per se does not reduce blood pressure in SHR with established hypertension and may increase the incidence of myocardial hypertrophy, depending on the form of exercise.
Orduña, Vladimir; Hong, Enrique; Bouzas, Arturo
An interval bisection procedure was used to study time discrimination in spontaneously hypertensive rats (SHR), which have been proposed as an animal model for the attention deficit hyperactivity disorder (ADHD); Wistar Kyoto and Wistar rats were used as comparison groups. In this procedure, after subjects learn to make one response (S) following a short duration stimulus, and another (L) following a long duration stimulus, stimuli of intermediate durations are presented, and the percentage of L is calculated for each duration. A logistic function is fitted to these data, and different parameters that describe the time discrimination process are obtained. Four conditions, with different short and long durations (1-4, 2-8, 3-12, 4-16s) were used. The results indicate that time discrimination is not altered in SHR, given that no difference in any of the parameters obtained were significant. Given that temporal processing has been proposed as a fundamental factor in the development of the main symptoms of ADHD, and that deficits in time discrimination have been found in individuals with that disorder, the present results suggest the necessity of exploring time perception in SHR with other procedures and sensory modalities, in order to assess its validity as an animal model of ADHD.
Pereira, Thiago Almeida; Syn, Wing-Kin; Pereira, Fausto E L; Lambertucci, José Roberto; Secor, William Evan; Diehl, Anna Mae
Schistosomiasis is a major cause of fibrosis and portal hypertension. The reason 4-10% of infected subjects develops hepatosplenic schistosomiasis remains unclear. Chronically infected male CBA/J mice reproduce the dichotomic forms of human schistosomiasis. Most mice (80%) develop moderate splenomegaly syndrome (similar to hepatointestinal disease in humans) and 20% present severe hypersplenomegaly syndrome (analogous to human hepatosplenic disease). We demonstrated that the profibrogenic molecule osteopontin discriminates between mice with severe and mild disease and could be a novel morbidity biomarker in murine and human schistosomiasis. Failure to downregulate osteopontin during the chronic phase may explain why hepatosplenic subjects develop severe fibrosis. Copyright Â© 2016. Published by Elsevier Ltd.
Henley, W.N.; Tucker, A.; Tran, T.N.; Stager, J.M.
The effect of altered thyroid metabolism on hypoxic moderation of hypertension was investigated, using three groups of spontaneously hypertensive rats: (1) surgically thyroidectomized (TX), (2) euthyroid (EU), and (3) TX with dietary hormone replacement (RPL). Each group was subdivided into hypoxic (H, 28 d at 3658 m simulated altitude) and normoxic (N, at 1525 m altitude). In all TX-H and TX-N rats, systolic blood pressure was attenuated. Thyroidectomy also decreased vessel responsiveness to KCl and isoproterenol, but hypoxia did not significantly change vessel responsiveness in either TX or EU rats. Vessels from RPL-N rats appeared to be euthyroid with respect to both isoproterenol and KCl responsiveness, while vessels from RPL-H showed a hyporesponsiveness characteristic of TX rats. It is argued that hypoxia and thyroidectomy mitigate systemic hypertension by different mechanisms. 24 references.
Aliev, O I; Anishchenko, A M; Sidekhmenova, A V; Shamanaev, A Yu; Fedorova, E P; Plotnikov, M B
SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.
Ueno, Mai; Tamura, Yuki; Toda, Natsuko; Yoshinaga, Mariko; Terakado, Shouko; Otsuka, Kie; Numabe, Atsushi; Kawabata, Yukari; Murota, Itsuki; Sato, Nobuyuki; Uehara, Yoshio
We investigated the effects of sodium alginate oligosaccharides (alginate) on the development of spontaneous hypertension in rats. Spontaneous hypertensive rats were treated with alginate for 7 weeks. Systolic blood pressure (SBP) and cardiovascular and kidney damage were assessed. Systolic blood pressure increased in SHRs and this elevation was attenuated with alginate treatment. The heart weight tended to decline. Alginate did not change plasma cholesterol levels or urinary sodium excretions. The slightly higher urinary protein excretion in SHRs was not changed with the treatment; however, morphologic glomerular damage was significantly attenuated. Sodium alginate oligosaccharide attenuates spontaneous hypertension in SHRs, and may help prevent early-stage kidney injury.
Hanafy, Amr Shaaban; El Hawary, Amr Talaat
Objectives: Evaluation of the outcome and experience in 2 years of management of portal hypertensive gastropathy (PHG) by argon plasma coagulation (APC) in a cohort of Egyptian cirrhotic patients. Methods: This study was conducted over a 2-year period from January 2011 to February 2013. Upper gastrointestinal endoscopy was performed to evaluate the degree and site of PHG. APC was applied to areas with mucosal vascular lesions. Results: In total, 200 cirrhotic patients were enrolled; 12 patients were excluded due to death (n = 6) caused by hepatic encephalopathy (n = 3), hepatorenal syndrome (n = 2), or chronic lymphatic leukemia (n = 1), or did not complete the treatment sessions (n = 6), so 188 patients completed the study. PHG was mainly fundic in 73 patients (38.8 %), corporeal in 66 patients (35.1 %), and pangastric in 49 patients (26.1 %) (P = 0.026). Patients were exposed to APC and received proton pump inhibitors together with propranolol at a dose sufficient to reduce the heart rate by 25 % or down to 55 beats/min. The mean (± standard deviation) number of sessions was 1.65 ± 0.8; six patients needed four sessions (3.2 %), 19 patients needed three sessions (10.1 %), 74 patients needed two sessions (39.4 %), and 89 patients needed one session (47.3 %). Patients with fundic and corporeal PHG required the lowest number of sessions (P = 0.000). Patients were followed up every 2 months for up to 1 year; the end point was a complete response with improved anemia and blood transfusion requirement which was achieved after one session in 89 patients (75.4 %), two sessions in 24 patients (20.3 %) and three sessions in five patients (4.3 %). A complete response was more prevalent in patients with corporeal and fundic PHG (P = 0.04). Conclusions: After 2 years’ experience in managing PHG, we found that a combination of APC and non-selective beta blockers was highly efficacious and safe in controlling
Pfeffer, J M; Pfeffer, M A; Frohlich, E D
The acute hemodynamic effects of the antihypertensive agent mebutamate were evaluated in spontaneously hypertensive and normotensive Wistar rats. Arterial and venous pressures and cardiac output (electromagnetic flowmeter) were recorded in artificially ventilated, open-chest, ether-anesthetized animals before and after varying doses of mebutamate were injected intravenously. In both normotensive and hypertensive rats mebutamate produced a moderate decrease in arterial pressure which was associated with a reduction in both heart rate and cardiac output; total peripheral resistance remained unchanged. These data suggest that mebutamate may have therapuetic value in reducing arterial pressure in mild to moderately severe hypertensive patients.
Nakamura, M; Ohishi, A; Watanabe, R; Kaneko, K; Aosaki, N; Iigaya, T; Monma, T; Sugiura, H; Miyoshi, Y; Hamaguchi, K
A 69-year-old female was admitted to our hospital because of leg edema, proteinuria (2.1 g/day), and gross hematuria. She had non-alcoholic liver cirrhosis of unknown etiology. Esophageal varices also were found. Examination of the renal biopsy specimen revealed mesangial proliferative glomerulonephritis with IgA deposits. Propranolol was administered orally to reduce portal hypertension, resulting in a progressive decrease in urinary microalbumin excretion. This case suggests that portal hypertension is involved in the pathogenesis of IgA nephropathy in liver cirrhosis.
Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E
The study of early development of the arterial hypertension in association with emotional stress is of great importance for better understanding of etiolody and pathogenesis of the hypertensive disease. MRI technique was applied to evaluate the hemodynamic and brain metabolites changes in 1- and 3-Mo-old ISIAH rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive WAG rats (8 male rats). In the 3-Mo-old ISIAH rats, age-dependent increase in the blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of abdominal aorta. The renal vascular resistance in the ISIAH rats decreased while aging, though, at both ages it remained higher than the renal vascular resistance in WAG rats. Integral metabolome portrait demonstrated that hypertension development in the ISIAH rats was associated with attenuation of excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats, the opposite age-dependent changes were observed. In contrast, in hypothalamus of 3-Mo-old ISIAH rats, an increase in energetic activity and prevalence of excitatory neurotransmitters over inhibitory was noticed. The blood flow through the main arteries showed positive correlation with glutamate and glutamine levels in hypothalamus, and negative one - with hypothalamic GABA level. The blood pressure values positively correlated with hypothalamic choline levels. Thus, the early development of the stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. This article is protected by copyright. All rights reserved.
de Macedo, Priscila Marques; Almeida-Paes, Rodrigo; Freitas, Dayvison Francis Saraiva; Brito-Santos, Fabio; Figueiredo-Carvalho, Maria Helena Galdino; de Almeida Soares, João Carlos; Freitas, Andrea D'Ávila; Zancopé-Oliveira, Rosely Maria; do Valle, Antonio Carlos Francesconi
Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole-trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.
Harris, G. W.; Ruf, K. B.
1. Ovulation was induced in Nembutal-blocked pro-oestrous rats by electrical stimulation of the hypothalamus. 2. The same type of electrical stimulation was applied during the collection of hypophysial portal blood. 3. Pooled hypophysial portal plasma from donors in pro-oestrus, oestrus and met-oestrus was assayed for ovarian ascorbic acid depleting (OAAD) activity. 4. Electrical stimulation of the hypothalamus increased the OAAD activity, believed to be due to luteinizing hormone releasing factor (LRF), in pro-oestrus and met-oestrus, but not in oestrus. 5. It is concluded that the hypothalamic nerve fibres responsible for releasing LRF into the hypophysial portal vessels are depleted of their store of this releasing factor, or are refractory to electrical stimulation, during oestrus. PMID:5499765
Zicha, J; Kunes, J
In this review, we attempt to outline the age-dependent interactions of principal systems controlling the structure and function of the cardiovascular system in immature rats developing hypertension. We focus our attention on the cardiovascular effects of various pharmacological, nutritional, and behavioral interventions applied at different stages of ontogeny. Several distinct critical periods (developmental windows), in which particular stimuli affect the further development of the cardiovascular phenotype, are specified in the rat. It is evident that short-term transient treatment of genetically hypertensive rats with certain antihypertensive drugs in prepuberty and puberty (at the age of 4-10 wk) has long-term beneficial effects on further development of their cardiovascular apparatus. This juvenile critical period coincides with the period of high susceptibility to the hypertensive effects of increased salt intake. If the hypertensive process develops after this critical period (due to early antihypertensive treatment or late administration of certain hypertensive stimuli, e.g., high salt intake), blood pressure elevation, cardiovascular hypertrophy, connective tissue accumulation, and end-organ damage are considerably attenuated compared with rats developing hypertension during the juvenile critical period. As far as the role of various electrolytes in blood pressure modulation is concerned, prohypertensive effects of dietary Na+ and antihypertensive effects of dietary Ca2+ are enhanced in immature animals, whereas vascular protective and antihypertensive effects of dietary K+ are almost independent of age. At a given level of dietary electrolyte intake, the balance between dietary carbohydrate and fat intake can modify blood pressure even in rats with established hypertension, but dietary protein intake affects the blood pressure development in immature animals only. Dietary protein restriction during gestation, as well as altered mother
Huebert, Robert C; Jagavelu, Kumaravelu; Hendrickson, Helen I; Vasdev, Meher M; Arab, Juan P; Splinter, Patrick L; Trussoni, Christy E; Larusso, Nicholas F; Shah, Vijay H
Changes in hepatic vasculature accompany fibrogenesis, and targeting angiogenic molecules often attenuates fibrosis in animals. Aquaporin-1 (AQP1) is a water channel, overexpressed in cirrhosis, that promotes angiogenesis by enhancing endothelial invasion. The effect of AQP1 on fibrogenesis in vivo and the mechanisms driving AQP1 expression during cirrhosis remain unclear. The purpose of this study was to test the effect of AQP1 deletion in cirrhosis and explore mechanisms regulating AQP1. After bile duct ligation, wild-type mice overexpress AQP1 that colocalizes with vascular markers and sites of robust angiogenesis. AQP1 knockout mice demonstrated reduced angiogenesis compared with wild-type mice, as evidenced by immunostaining and endothelial invasion/proliferation in vitro. Fibrosis and portal hypertension were attenuated based on immunostaining, portal pressure, and spleen/body weight ratio. AQP1 protein, but not mRNA, was induced by hyperosmolality in vitro, suggesting post-transcriptional regulation. Endothelial cells from normal or cirrhotic mice were screened for microRNA (miR) expression using an array and a quantitative PCR. miR-666 and miR-708 targeted AQP1 mRNA and were decreased in cirrhosis and in cells exposed to hyperosmolality, suggesting that these miRs mediate osmolar changes via AQP1. Binding of the miRs to the untranslated region of AQP1 was assessed using luciferase assays. In conclusion, AQP1 promotes angiogenesis, fibrosis, and portal hypertension after bile duct ligation and is regulated by osmotically sensitive miRs.
Luisa, Siciliani; Vitale, Giovanna; Sorbo, Anna Rita; Maurizio, Pompili; Lodovico, Rapaccini Gian
It has been demonstrated that Doppler waveform of the hepatic vein (normally triphasic) is transformed into a biphasic or monophasic waveform in cirrhotic patients. The compressive mechanism of liver tissue has been considered up till now the cause of this change. Moreover, cirrhotics show, after USCA injection, a much earlier HVTT due to intrahepatic shunts. Our aim was to prospectively evaluate the correlation between Doppler pattern of hepatic vein and HVTT of a second-generation USCA; we also correlated HVTT with the most common indexes of portal hypertension. We enrolled 38 participants: 33 cirrhotics and 5 healthy controls. Doppler shift signals were obtained from the right hepatic vein. To characterize the hepatic vein pattern, we used the hepatic vein waveform index (HVWI). This index becomes >1 with the appearance of the triphasic waveform. We recorded a clip from 20 s before to 2 min after a peripheral intravenous bolus injection of 2.4 ml of USCA (sulfur hexafluoride).The time employed by USCA to cross the liver from the hepatic artery and portal vein to the hepatic vein was defined as HA-HVTT and PV-HVTT, respectively. Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time (p < 0.001). HVTT was earlier as MELD, Child-Pugh score and spleen diameter increased. Patients with ascites and varices of large size had significantly shorter transit times. Abnormal hepatic vein Doppler waveform in cirrhotic patients could be due to intrahepatic shunts. HVTT could be useful in the non-invasive evaluation of portal hypertension.
Gouya, Hervé; Grabar, Sophie; Vignaux, Olivier; Saade, Anastasia; Pol, Stanislas; Legmann, Paul; Sogni, Philippe
To measure azygos, portal and aortic flow by two-dimensional cine phase-contrast magnetic resonance imaging (2D-cine PC MRI), and to compare the MRI values to hepatic venous pressure gradient (HVPG) measurements, in patients with cirrhosis. Sixty-nine patients with cirrhosis were prospectively included. All patients underwent HVPG measurements, upper gastrointestinal endoscopy and 2D-cine PC MRI measurements of azygos, portal and aortic blood flow. Univariate and multivariate regression analyses were used to evaluate the correlation between the blood flow and HVPG. The performance of 2D-cine PC MRI to diagnose severe portal hypertension (HVPG ≥ 16 mmHg) was determined by receiver operating characteristic curve (ROC) analysis, and area under the curves (AUC) were compared. Azygos and aortic flow values were associated with HVPG in univariate linear regression model. Azygos flow (p < 10(-3)), aortic flow (p = 0.001), age (p = 0.001) and presence of varices (p < 10(-3)) were independently associated with HVPG. Azygos flow (AUC = 0.96 (95 % CI [0.91-1.00]) had significantly higher AUC than aortic (AUC = 0.64 (95 % CI [0.51-0.77]) or portal blood flow (AUC = 0.40 (95 % CI [0.25-0.54]). 2D-cine PC MRI is a promising technique to evaluate significant portal hypertension in patients with cirrhosis. • Noninvasive HVPG assessment can be performed with MRI azygos flow. • Azygos MRI flow is an easy-to-measure marker to detect significant portal hypertension. • MRI flow is more specific that varice grade to detect portal hypertension.
The possible existence of the same pattern of porto-caval connection in dogs having a single congenital portosystemic shunt (CPSS) and in dogs having multiple acquired portosystemic shunt (MAPSS) secondary to portal hypertension (PH) was evaluated. Retrospective evaluation of all CT examinations of patients having portosystemic shunt (PSS) was performed in a 4-year time period. All anomalous porto-caval connections were assessed for anatomical pattern and compared with published veterinary literature. Records of 25 dogs were reviewed. 16 dogs had a single CPSS (CPSS group), and 9 dogs had multiple acquired PSS secondary to PH (APSS group). The splenophrenic shunt pattern was found in 3 dogs of the CPSS group as a single congenital anomaly without PH and in 2 dogs of the APSS group associated with MAPSS and ascites due to different hepatic diseases causing PH. These findings corroborate two hypotheses: 1) Splenophrenic PSS should be considered as a classical CPSS but if this is not sufficient to alleviate a PH developed after birth because of eventual hepatic or portal diseases, in this case ascites and acquired portal collaterals may develop. In this case, MAPSS and CPSS may coexist. 2) The pattern of splenophrenic PSS, classically described among CPSS, may develop as acquired portal collateral in dogs with PH and it should also be included in the category of APSS. These preliminary findings may be helpful in reconsidering the classical haemodynamics of porto-caval diseases, enrich the classification of APSS in dogs and refine the imaging evaluation of patients with PH. PMID:27882305
Zimmerman, J B; Robertson, D; Jackson, E K
This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release. PMID:3301900
Kobashi, M; Mizutani, M; Adachi, A
The effects of the portal infusion of hyper- and hypotonic solution on gastric motility in rats were investigated. The infusion of hypertonic saline into the portal vein (portal infusion) elicited a significant enhancement of gastric contractile activity. The portal infusion of water also produced this enhancement. However, the portal infusion of isotonic saline showed no significant enhancement; nor did the infusion of water and hypertonic saline into the jugular vein. Sectioning of the hepatic branch of the vagus nerve (hepatic vagus) eliminated the enhanced responses of the gastric motility. It is therefore concluded that hepatoportal osmoreceptive afferent signals affect the gastric motility by way of the hepatic vagus. These effects on osmolarity revealed that hypotonic stimulation is more effective than hypertonic stimulation for the enhancement of motility. Sectioning of the dorsal subdiaphragmatic vagus, which includes the dorsal gastric and celiac branch, did not eliminate these responses. Sectioning of the ventral gastric vagus, in contrast, did eliminate the responses. These results suggest that vagal preganglionic neurons in the left dorsal motor nucleus of the vagus play a role in enhancement of gastric motility observed in the present research.
Simms, Annabel E; Paton, Julian F R; Pickering, Anthony E; Allen, Andrew M
Sympathetic nerve activity (SNA) is elevated in established hypertension. We tested the hypothesis that SNA is elevated in neonate and juvenile spontaneously hypertensive (SH) rats prior to the development of hypertension, and that this may be due to augmented respiratory–sympathetic coupling. Using the working heart–brainstem preparation, perfusion pressure, phrenic nerve activity and thoracic (T8) SNA were recorded in male SH rats and normotensive Wistar–Kyoto (WKY) rats at three ages: neonates (postnatal day 9–16), 3 weeks old and 5 weeks old. Perfusion pressure was higher in SH rats at all ages reflecting higher vascular resistance. The amplitude of respiratory-related bursts of SNA was greater in SH rats at all ages (P < 0.05). This was reflected in larger Traube–Hering pressure waves in SH rats (1.4 ± 0.8 versus 9.8 ± 1.5 mmHg WKY versus SH rat, 5 weeks old, n= 5 per group, P < 0.01). Recovery from hypocapnic-induced apnoea and reinstatement of Traube–Hering waves produced a significantly greater increase in perfusion pressure in SH rats (P < 0.05). Differences in respiratory–sympathetic coupling in the SH rat were not secondary to changes in central or peripheral chemoreflex sensitivity, nor were they related to altered arterial baroreflex function. We have shown that increased SNA is already present in SH rats in early postnatal life as revealed by augmented respiratory modulation of SNA. This is reflected in an increased magnitude of Traube–Hering waves resulting in elevated perfusion pressure in the SH rat. We suggest that the amplified respiratory-related bursts of SNA seen in the neonate and juvenile SH rat may be causal in the development of their hypertension. PMID:19064613
Queiroz, Thyago M; Guimarães, Drielle D; Mendes-Junior, Leônidas G; Braga, Valdir A
Renovascular hypertension has robust effects on control of blood pressure, including an impairment in baroreflex mechanisms, which involves oxidative stress. Although α-lipoic acid (LA) has been described as a potent antioxidant, its effect on renovascular hypertension and baroreflex sensitivity (BRS) has not been investigated. In the present study we analyzed the effects caused by chronic treatment with LA on blood pressure, heart rate and baroreflex sensitivity (sympathetic and parasympathetic components) in renovascular hypertensive rats. Male Wistar rats underwent 2-Kidney-1-Clip (2K1C) or sham surgery and were maintained untouched for four weeks to develop hypertension. Four weeks post-surgery, rats were treated with LA (60 mg/kg) or saline for 14 days orally. On the 15th day mean arterial pressure (MAP) and heart rate (HR) were recorded. In addition, baroreflex sensitivity test using phenylephrine (8 µg/kg, i.v.) and sodium nitroprusside (25 µg/kg, i.v.) was performed. Chronic treatment with LA decreased blood pressure in hypertensive animals; however, no significant changes in baseline HR were observed. Regarding baroreflex, LA treatment increased the sensitivity of both the sympathetic and parasympathetic components. All parameters studied were not affected by treatment with LA in normotensive animals. Our data suggest that chronic treatment with LA promotes antihypertensive effect and improves baroreflex sensitivity in rats with renovascular hypertension.
Lopez-Campistrous, Ana; Hao, Li; Xiang, Wang; Ton, Dong; Semchuk, Paul; Sander, Joerg; Ellison, Michael J; Fernandez-Patron, Carlos
The central nervous system plays a critical role in the normal control of arterial blood pressure and in its elevation in virtually all forms of hypertension. Mitochondrial dysfunction has been increasingly associated with the development of hypertension. Therefore, we examined whether mitochondrial dysfunction occurs in the brain in hypertension and characterized it at the molecular scale. Mitochondria from whole brain and brain stem from 12-week-old spontaneously hypertensive rats with elevated blood pressure (190+/-5 mm Hg) were compared against those from age-matched normotensive (134+/-7 mm Hg) Wistar Kyoto rats (n=4 in each group). Global differential analysis using 2D electrophoresis followed by tandem mass spectrometry-based protein identification suggested a downregulation of enzymes involved in cellular energetics in hypertension. Targeted differential analysis of mitochondrial respiratory complexes using the classical blue-native SDS-PAGE/Western method and a complementary combination of sucrose-gradient ultracentrifugation/tandem mass spectrometry revealed previously unknown assembly defects in complexes I, III, IV, and V in hypertension. Interestingly, targeted examination of the brain stem, a regulator of cardiovascular homeostasis and systemic blood pressure, further showed the occurrence of mitochondrial complex I dysfunction, elevated reactive oxygen species production, decreased ATP synthesis, and impaired respiration in hypertension. Our findings suggest that in already-hypertensive spontaneously hypertensive rats, the brain respiratory complexes exhibit previously unknown assembly defects. These defects impair the function of the mitochondrial respiratory chain. This mitochondrial dysfunction localizes to the brain stem and is, therefore, likely to contribute to the development, as well as to pathophysiological complications, of hypertension.
Kobashi, M; Adachi, A
To determine whether or not hepatoportal osmoreceptive (or sodium-receptive) signals participate in the control of drinking, we examined the effects of portal infusion of water, 0.9% saline, and 1.8% saline on water intake by water-deprived rats. Infusion was started 0.5 h prior to the end of the water deprivation period for 3.5 h at a rate of 52 microliters/min through either a portal or a jugular catheter. After 24-h water deprivation, water intake was measured successively for 24 h without food. As a result of the water infusion tests, water intake of the portal infusion group was significantly less than that of the jugular infusion group during and after the infusion. Portal infusion of neither 0.9% nor 1.8% saline affected the water intake compared to similar infusion into the jugular vein. It is concluded that hypotonic stimulation of the hepatoportal osmoreceptor suppresses water intake in water-deprived rats. On the contrary, isotonic or hypertonic stimulation does not produce any change of water intake.
Zhou, Li-Min; Zhu, Guo-Qing; Wang, Han-Jun; Zhao, Cong-Kan; Xu, Yao; Gao, Xing-Ya
The authors' previous study showed a closed-loop chip system that was used to control arterial pressure in normal rabbits and rats. In the present study the anti-hypertensive effects of the chip system were investigated in anaesthetized two-kidney one-clip (2K1C) renovascular hypertensive rats and compared with sham-operated rats. The chip system recorded, sampled, and processed the signals of arterial pressure and instantaneously controlled arterial pressure by stimulating the left aortic depressor nerve. The frequency of stimulation was determined according to the feedback signals of arterial pressure. The chip system, running three different programs, successfully achieved a different degree of depressor effects. It effectively decreased not only mean arterial pressure (MAP), but also renal sympathetic nerve activity (RSNA) in both 2K1C rats and sham-operated rats. The chip system significantly increased the baroreflex gain in the 2K1C rats, but not in the sham-operated rats. It normalized the increased left ventricle developing pressure and maximal rise rate of the left ventricle pressure (dP/dtmax) in the 2K1C rats. These results indicate that the depressor effect can be controlled by changing the programs of the chip system. The closed-loop chip system effectively decreased arterial pressure and sympathetic outflow, increased baroreflex gain, and normalized the enhanced cardiac contractility in renovascular hypertensive rats.
Nicholas, T. E.
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
Wu, Gang; Bao, Xuhui; Xi, Guohua; Keep, Richard; Thompson, B. Gregory; Hua, Ya
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
Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.
The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension.
Qayyum, Aliya; Lee, Gerard K; Yeh, Benjamin M; Allen, Jill N; Venook, Alan P; Coakley, Fergus V
This study aimed to determine the frequency of hepatic contour abnormalities and signs of portal hypertension at serial CT in patients receiving chemotherapy for breast cancer metastatic to the liver. We retrospectively identified 91 women with breast cancer metastatic to the liver who received chemotherapy and underwent serial CT at our institution between 1998 and 2002. Two readers independently categorized hepatic contour abnormalities on the final CT examination as none, limited retraction, widespread retraction, or diffuse nodularity. Readers also recorded the development of hepatic atrophy or enlargement, ascites, portosystemic collateral veins, and splenomegaly. Interpretative discrepancies were resolved by consensus. Portal hypertension was defined as the presence of at least two of the following CT signs: simple ascites, portosystemic collateral veins, and splenomegaly. After a median follow-up interval of 15 months (range, 1-46), hepatic contour abnormalities were seen in 68 of 91 patients (75%) and consisted of limited retraction (n = 42), widespread retraction (n = 10), or diffuse nodularity (n = 16). Portal hypertension was found in 1 of 23 patients without contour abnormalities, in 1 of 42 patients with limited retraction, in none of 10 patients with widespread retraction, and in 6 of 16 patients with diffuse nodularity (P < .01). Hepatic contour abnormalities commonly develop at serial CT in patients undergoing chemotherapy for breast cancer metastatic to the liver and may be accompanied by signs of portal hypertension; the latter are particularly, but not exclusively, associated with the development of diffuse hepatic nodularity.
Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina
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
Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina
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.
Kumarasamy, Sivarajan; Gopalakrishnan, Kathirvel; Shafton, Asher; Nixon, Jeremy; Thangavel, Jayakumar; Farms, Phyllis; Joe, Bina
Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes.
Maruyama, H; Okugawa, H; Kobayashi, S; Yoshizumi, H; Takahashi, M; Ishibashi, H; Yokosuka, O
Objectives The aim of this prospective study was to elucidate the efficacy of contrast-enhanced three-dimensional (3D) ultrasound with Sonazoid® (GF Healthcare, Oslo, Norway) as a non-invasive tool to discriminate idiopathic portal hypertension (IPH) from cirrhosis by demonstration of portal vein structure. Methods There were 16 patients: 11 with biopsy-proven cirrhosis and 5 with biopsy-proven IPH. Intrahepatic right portal vein images were taken by 3D ultrasound from 1 min after the injection of Sonazoid (0.0075 ml kg–1). Portal vein appearances were compared between 3D ultrasound and percutaneous transhepatic portography (PTP) by four independent reviewers. Sensitivity, specificity and area under the receiver operating characteristic curve (Az) of the images were used for the diagnosis of cirrhosis/IPH, and interimaging, inter-reviewer and interoperator agreement were examined. Results Sensitivity, specificity and Az of PTP for the diagnosis of cirrhosis/IPH were 63.6%/100%, 100% and 0.9 (0.71–1.0) by Reviewer I and 90.9%/100%, 100% and 1.0 by Reviewer III, respectively. Similarly, sensitivity, specificity and Az of 3D ultrasound for diagnosis of cirrhosis/IPH were 54.5%/80%, 100% and 0.96 (0.84–1.0) by Reviewer II and 72.7%/80%, 100% and 0.97 (0.9–1.0) by Reviewer IV, respectively. Diagnostic agreement between PTP and 3D ultrasound was good between Reviewers I and II (κ=0.793) and good between Reviewers III and IV (κ=0.732). Inter-reviewer agreement was good between Reviewers I and III for PTP diagnosis (κ=0.735), and good between Reviewers II and IV for 3D ultrasound diagnosis (κ=0.792). Interoperator agreement of diagnostic results was good (κ=0.740). Conclusion Non-invasive visualisation of intrahepatic portal vein structure by contrast-enhanced 3D ultrasound with Sonazoid may have the potential to discriminate IPH from cirrhosis. PMID:21343319
Jalan, Rajiv; De Chiara, Francesco; Balasubramaniyan, Vairappan; Andreola, Fausto; Khetan, Varun; Malago, Massimo; Pinzani, Massimo; Mookerjee, Rajeshwar P; Rombouts, Krista
with the ammonia lowering drug OP reduces portal pressure and deactivates hHSC in vivo, highlighting the opportunity for evaluating ammonia lowering as a potential therapy in cirrhotic patients with portal hypertension. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Zuccollo, Adriana; Navarro, Monica
The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group, of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes. PMID:12369707
Aguilar-Olivos, Nancy Edith; de León-Monterroso, José Luis; Avila-Escobedo, Lourdes; López-Méndez, Eric
Antecedentes: la biliopatía por hipertensión portal es poco diagnosticada debido a que sólo algunos pacientes experimentan síntomas. Las manifestaciones clínicas más importantes son la colestasis y la colangitis. Objetivo: comunicar una serie de casos evaluados, tratados y seguidos en una institución pública de tercer nivel. Casos clínicos: cuatro pacientes con biliopatía por hipertensión portal se expusieron a diferentes métodos para tratar la hipertensión portal y la descompresión de la vía biliar. Se realizó seguimiento durante casi cinco años. Tres casos mostraron adecuada evolución, con remisión de los síntomas; un paciente falleció al intentar dilatarle la vía biliar. Finalmente, se revisa la bibliografía en relación con la terapéutica de la biliopatía por hipertensión portal. Conclusiones: no existe consenso para el tratamiento óptimo de este padecimiento, aunque el objetivo es descomprimir la vía biliar; cada caso plantea particularidades que guían el tratamiento.
Rosenthal, Talma; Younis, Firas; Alter, Ariela
Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment. PMID:27713282
Tamashiro, H.; Arakaki, M.; Akagi, H.; Hirayama, K.; Murao, K.; Smolensky, M.H.
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.
Paramaguru, Rajaguru; Kumar, Lijesh; Shenoy, Padmanabha; Augustine, Philip
Nodular regenerative hyperplasia (NRH) is a rare liver condition in which widespread benign transformation of the hepatic parenchyma into small regenerative nodules occur, leading to development of non-cirrhotic portal hypertension. Conditions associated with NRH include rheumatologic, hematological, autoimmune, infectious, neoplastic, or drug-related etiology. Accurate diagnosis is made on liver biopsy, showing diffuse micronodular transformation in the absence of fibrosis. Here, we present the second case in world literature of a middle-aged man presenting with recent onset sleep reversal and memory loss with darkening of skin for four years associated with systemic manifestations, in whom porto-systemic shunt syndrome due to NRH secondary to Behcet’s disease was eventually diagnosed. PMID:28465872
Javkhedkar, Apurva A.; Quiroz, Yasmir; Rodriguez-Iturbe, Bernardo; Vaziri, Nosratola D.; Lokhandwala, Mustafa F.
Compelling evidence supports the role of oxidative stress and renal interstitial inflammation in the pathogenesis of hypertension. Resveratrol is a polyphenolic stilbene, which can lower oxidative stress by activating the transcription factor nuclear factor-E2-related factor-2 (Nrf2), the master regulator of numerous genes encoding antioxidant and phase II-detoxifying enzymes and molecules. Given the role of oxidative stress and inflammation in the pathogenesis of hypertension, we conducted this study to test the hypothesis that long-term administration of resveratrol will attenuate renal inflammation and oxidative stress and, hence, progression of hypertension in the young spontaneously hypertensive rats (SHR). SHR and control [Wistar-Kyoto (WKY)] rats were treated for 9 wk with resveratrol or vehicle in their drinking water. Vehicle-treated SHR exhibited renal inflammatory injury and oxidative stress, as evidenced by glomerulosclerosis, tubulointerstitial injury, infiltration of inflammatory cells, and increased levels of renal 8-isoprostane and protein carbonylation. This was associated with reduced antioxidant capacity and downregulations of Nrf2 and phase II antioxidant enzyme glutathione-S-transferase (GST). Resveratrol treatment mitigated renal inflammation and injury, reduced oxidative stress, normalized antioxidant capacity, restored Nrf2 and GST activity, and attenuated the progression of hypertension in SHR. However, resveratrol had no effect on these parameters in WKY rats. In conclusion, development and progression of hypertension in the SHR are associated with inflammation, oxidative stress, and impaired Nrf2-GST activity in the kidney. Long-term administration of resveratrol restores Nrf2 expression, ameliorates inflammation, and attenuates development of hypertension in SHR. Clinical studies are needed to explore efficacy of resveratrol in human hypertension. PMID:25761698
Javkhedkar, Apurva A; Quiroz, Yasmir; Rodriguez-Iturbe, Bernardo; Vaziri, Nosratola D; Lokhandwala, Mustafa F; Banday, Anees A
Compelling evidence supports the role of oxidative stress and renal interstitial inflammation in the pathogenesis of hypertension. Resveratrol is a polyphenolic stilbene, which can lower oxidative stress by activating the transcription factor nuclear factor-E2-related factor-2 (Nrf2), the master regulator of numerous genes encoding antioxidant and phase II-detoxifying enzymes and molecules. Given the role of oxidative stress and inflammation in the pathogenesis of hypertension, we conducted this study to test the hypothesis that long-term administration of resveratrol will attenuate renal inflammation and oxidative stress and, hence, progression of hypertension in the young spontaneously hypertensive rats (SHR). SHR and control [Wistar-Kyoto (WKY)] rats were treated for 9 wk with resveratrol or vehicle in their drinking water. Vehicle-treated SHR exhibited renal inflammatory injury and oxidative stress, as evidenced by glomerulosclerosis, tubulointerstitial injury, infiltration of inflammatory cells, and increased levels of renal 8-isoprostane and protein carbonylation. This was associated with reduced antioxidant capacity and downregulations of Nrf2 and phase II antioxidant enzyme glutathione-S-transferase (GST). Resveratrol treatment mitigated renal inflammation and injury, reduced oxidative stress, normalized antioxidant capacity, restored Nrf2 and GST activity, and attenuated the progression of hypertension in SHR. However, resveratrol had no effect on these parameters in WKY rats. In conclusion, development and progression of hypertension in the SHR are associated with inflammation, oxidative stress, and impaired Nrf2-GST activity in the kidney. Long-term administration of resveratrol restores Nrf2 expression, ameliorates inflammation, and attenuates development of hypertension in SHR. Clinical studies are needed to explore efficacy of resveratrol in human hypertension. Copyright © 2015 the American Physiological Society.
Yamaguchi, Y.; Yamaguchi, K.; Babb, J.L.; Gans, H.
The in vivo uptake of endotoxin by the liver from portal vein blood was assessed during a single passage through the liver. /sup 51/Cr labeled and unlabeled endotoxin were infused in different amounts into the femoral vein of three groups of lead-sensitized rats: a nonoperated, a sham-operated, and a surgically created reversed Eck fistula (REF) group. Whereas in the former two the infused endotoxin encounters the lung as the first filter organ, the liver performs this function in the latter experimental model. The mortality rates observed in control and sham-operated, lead-sensitized rats were found to correlate closely and reproducibly to the degree of endotoxemia. This assay was then applied to determine the amount of endotoxin eliminated by the liver by establishing, in the REF rat, the amounts of endotoxin that escaped hepatic clearance. The capacity of the liver to eliminate endotoxin from portal vein blood during a single passage increases as the portal vein endotoxin level rises; it approaches a maximum, suggesting that endotoxin's interaction with the Kupffer cells conforms to classical saturation kinetics. A Lineweaver-Burk plot prepared from these data indicates that the maximal in vivo capacity of the liver to remove endotoxin from portal vein blood approximates 1.5 micrograms/gm liver/hr. Data obtained with the use of radiolabeled endotoxin corroborate the information obtained with the bioassay technique. Endotoxin eliminated by the Kupffer cells in these quantities is slowly disintegrated; 4 hr after termination of the endotoxin infusion, less than 4% of the radiolabel is found in the urine and none in the bile. These observations indicate that the Kupffer cell's functional capacity to sequester and detoxify endotoxin is extensive and far exceeds the requirements imposed by physiological and most pathological conditions.
de Queirós, Andréa Simone Siqueira; Brandão, Simone Cristina Soares; Domingues, Ana Lúcia Coutinho; Macedo, Liana Gonçalves; Ourem, Maira Souto; Lopes, Edmundo Pessoa Almeida
Background Portal hypertension is responsible for various complications in patients with schistosomiasis, among them intrapulmonary vascular dilations (IPVD). In cirrhotic patients the presence of IPVD is a sign of poor prognosis, but in patients with hepatosplenic schistosomiasis (HSS) there are no studies assessing the significance of this change. The aim of this study was to evaluate the occurrence of IPVD through 99mTc-MAA scintigraphy in patients with HSS and its relationship with clinical, laboratory, endoscopic and ultrasound parameters. Methods Cross-sectional study evaluating 51 patients with HSS. Patients were diagnosed with IPVD when the brain uptake of 99mTc-MAA was higher than 6%. Subsequently, they were divided according to presence (G1) or absence (G2) of IPVD and variables were compared between groups. Results Overall, 51 patients with mean age of 56±12 years were assessed. IPVD was observed in 31 patients (60%). There was no statistically significant differences between groups when clinical, laboratory and endoscopic parameters were compared. Regarding ultrasound parameters, the splenic vein diameter was smaller in G1 (0.9±0.3 cm) compared to G2 (1.2±0.4 cm), p = 0.029. Conclusion In patients with HSS, the occurrence of IPVD by 99mTc-MAA scintigraphy was high and was associated with lower splenic vein diameter, which can be a mechanism of vascular protection against portal hypertension. However, more studies are needed to determine the clinical significance of the early diagnosis and natural evolution of IPVD in this population. PMID:24967578
Planella de Rubinat, Montserrat; Teixidó Amorós, Montserrat; Ballester Clau, Raquel; Trujillano Cabello, Javier; Ibarz Escuer, Mercedes; Reñé Espinet, Josep Maria
There are few studies on iron deficiency anemia (IDA) after non-variceal acute upper gastrointestinal bleeding (UGIB) in patients without portal hypertension. To define the incidence of IDA after UGIB, to characterize the predictive factors for IDA and to design algorithms that could help physicians identify those patients who could benefit from iron therapy. We registered 391 patients with UGIB between April 2007 and May 2009. Patients with portal hypertension and those with clinical or/and biological conditions that could affect the ferrokinetic pattern were excluded. Blood analyses were performed, including ferric parameters upon admission, on the 5th day, and on the 30th day after the hemorrhage episode. We used a multiple logistic regression model and a classification and regression tree model. A total of 124 patients were included, of which 76 (61.3%) developed IDA 30 days after UGIB. The predictive variables were age >75 years (P=.037; OR 3.9; 95% CI: 1.3-11.6), initial urea level >80mg/dL (P=.027; OR 2.9; 95% CI: 1.1-7.6), initial ferritin level ≤65ng/dL (P=.002; OR 7.6; 95% CI: 2.9-18.5), initial hemoglobin level ≤100g/L (P=.003; OR 3.2; 95% CI: 1.3-8.0), hemoglobin level on the 5th day ≤100g/L (P<.001; OR 14.9; 95% CI: 3.6-61.1) and the value of the transferrin saturation index on the 5th day <10% (p<0.001; OR 7.2; 95% CI: 2.6-20.3). Most patients with UGIB developed IDA 30 days after the episode. Identification of the predictive factors for IDA may help to establish guidelines for the administration of iron therapy. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.
Cates, Matthew J; Steed, Peter W; Abdala, Ana P L; Langton, Philip D; Paton, Julian F R
There is a strong correlation between increased vertebral artery resistance and arterial blood pressure in humans. The reasons for this increased resistance at high systemic pressure remain unknown, but may include raised sympathetic activity. With the recent finding that prehypertensive spontaneously hypertensive (PHSH) rats, which have raised sympathetic nerve activity, but a blood pressure comparable to normotensive rat strains, we hypothesized that its vertebrobasilar vascular resistance would already be raised and, as a consequence, would exhibit a more responsive Cushing response (e.g., brain ischemia evoked sympathoexcitation and a pressor response). We report that PHSH rats exhibited a remodeling of the basilar artery (i.e., increased wall thickness and lower lumen-to-wall thickness ratio) that occurred before the onset of hypertension. In a novel in vitro vascularly isolated, arterially perfused brain stem preparation of PHSH rats of 4-5 wk of age, brain stem vascular resistance was raised by ∼35% relative to age- and sex-matched normotensive rats (P < 0.05). In the in situ arterial perfused working heart-brain stem preparation, occlusion of both vertebral arteries in the PHSH rat resulted in a significantly greater increase in sympathetic activity (57 vs. 20%, PHSH vs. control; P < 0.01) that triggered a greater increase in arterial perfusion pressure (8 vs. 3 mmHg, PHSH vs. control; P < 0.01) compared with normotensive rats. These data indicate raised vertebrobasilar artery resistance before the onset of hypertension in the PHSH rat. With the raised responsiveness of the Cushing response in the PHSH rat, we discuss the possibility of brain stem perfusion as a central nervous system determinant of the set point of vasomotor sympathetic tone in the hypertensive condition.
Cates, Matthew J.; Steed, Peter W.; Abdala, Ana P. L.; Langton, Philip D.
There is a strong correlation between increased vertebral artery resistance and arterial blood pressure in humans. The reasons for this increased resistance at high systemic pressure remain unknown, but may include raised sympathetic activity. With the recent finding that prehypertensive spontaneously hypertensive (PHSH) rats, which have raised sympathetic nerve activity, but a blood pressure comparable to normotensive rat strains, we hypothesized that its vertebrobasilar vascular resistance would already be raised and, as a consequence, would exhibit a more responsive Cushing response (e.g., brain ischemia evoked sympathoexcitation and a pressor response). We report that PHSH rats exhibited a remodeling of the basilar artery (i.e., increased wall thickness and lower lumen-to-wall thickness ratio) that occurred before the onset of hypertension. In a novel in vitro vascularly isolated, arterially perfused brain stem preparation of PHSH rats of 4–5 wk of age, brain stem vascular resistance was raised by ∼35% relative to age- and sex-matched normotensive rats (P < 0.05). In the in situ arterial perfused working heart-brain stem preparation, occlusion of both vertebral arteries in the PHSH rat resulted in a significantly greater increase in sympathetic activity (57 vs. 20%, PHSH vs. control; P < 0.01) that triggered a greater increase in arterial perfusion pressure (8 vs. 3 mmHg, PHSH vs. control; P < 0.01) compared with normotensive rats. These data indicate raised vertebrobasilar artery resistance before the onset of hypertension in the PHSH rat. With the raised responsiveness of the Cushing response in the PHSH rat, we discuss the possibility of brain stem perfusion as a central nervous system determinant of the set point of vasomotor sympathetic tone in the hypertensive condition. PMID:21493719
Perlstein, M I; Bissada, N F
The purpose of this investigation was to evaluate the extent to which obesity and/or hypertension may modify the response of rats' periodontium to chronic gingival irritation. Forty-four normal, spontaneously hypertensive, obese, and obese-hypertensive rats were used. Histopathologic evaluation of the periodontal structure showed both hyperplasia and hypertrophy of the walls of blood vessels supplying the periodontium in the hypertensive and obese-hypertensive animals. The results also indicated that obesity significantly contributed to e severity of periodontal disease. Hypertension alone was not a significant factor. The obese-hypertensive rats showed the most severe periodontal response to local irritation.
Adnan, Sareema; Nelson, James W; Ajami, Nadim J; Venna, Venugopal R; Petrosino, Joseph F; Bryan, Robert M; Durgan, David J
Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled. Similarly, cecal contents from normotensive WKY rats were pooled. Four-week-old recipient WKY and SHR rats, previously treated with antibiotics to reduce the native microbiota, were gavaged with WKY or SHRSP microbiota, resulting in four groups; WKY with WKY microbiota (WKY g-WKY), WKY with SHRSP microbiota (WKY g-SHRSP), SHR with SHRSP microbiota (SHR g-SHRSP), and SHR with WKY microbiota (SHR g-WKY). Systolic blood pressure (SBP) was measured weekly using tail-cuff plethysmography. At 11.5 wk of age systolic blood pressure increased 26 mmHg in WKY g-SHRSP compared with that in WKY g-WKY (182 ± 8 vs. 156 ± 8 mmHg, P = 0.02). Although the SBP in SHR g-WKY tended to decrease compared with SHR g-SHRSP, the differences were not statistically significant. Fecal pellets were collected at 11.5 wk of age for identification of the microbiota by sequencing the 16S ribosomal RNA gene. We observed a significant increase in the Firmicutes:Bacteroidetes ratio in the hypertensive WKY g-SHRSP, as compared with the normotensive WKY g-WKY (P = 0.042). Relative abundance of multiple taxa correlated with SBP. We conclude that gut dysbiosis can directly affect SBP. Manipulation of the gut microbiota may represent an innovative treatment for hypertension.
Aprigliano, O; Hermsmeyer, K
Adrenergic denervation of the rat portal vein was produced in vivo by the sympatholytic agent 6-hydroxydopamine (6-OHDA). Treatment of rats with 6-OHDA decreased the responses of the portal veins to nerve stimulation, reduced 3H-norepinephrine (NE) uptake, and decreased catecholamine fluorescence, indicating that partial adrenergic denervation was achieved. The main findings of this study indicate that the in vivo denervation produced: (1) a (time-dependent) increase in sensitivity of the veins to NE, which was not of prejunctional origin, (2) an increase in sensitivity to BaC12, and (3) a partial depolarization of the myovascular cells. The results suggest that the in vivo denervation of the portal veins by 6-OHDA produces a postjunctional alteration, which may be due to the removal of a trophic influence of the sympathetic nervous system. It is proposed that the partial depolarization and associated ionic changes may be components of the mechanism. These results provide the first direct evidence that membrane excitability changes are involved in trophic nerve-muscle interactions in blood vessels.
Oxenkrug, Gregory F; Summergrad, Paul
The neuroendocrine theory of aging suggests the common mechanisms of developmental (prereproductive) and aging (postreproductive) processes and identified a cluster of conditions (hypertension, obesity, dyslipidemia, type 2 diabetes, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer) as age-associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndrome (MetS). Because melatonin attenuated development of MetS is age-dependent, that is, in young and old, but not in middle-aged rats, we studied the effect of the selective melatonin agonist, Ramelteon, on the two core symptoms of MetS/AAND: hypertension and body weight gain in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto male rats (WKY). SHR rats developed hypertension at the time of maximal weight gain that coincided with the onset of reproductive activity (8-10 weeks old). Chronic (but not acute) administration of Ramelteon (in drinking water, 8 mg/kg/day, from 4 to 12 weeks of age) attenuated age-associated increase of systolic blood pressure (tail-cuff method) by 45%, and age-associated body weight gain by 30%. Acute and chronic Ramelteon did not affect blood pressure and body weight in normotensive WKY rats. Ramelteon-induced attenuation of age-associated hypertension and weight gain suggests that Ramelteon might attenuate the other symptoms of MetS/AAND and might be useful in the treatment of MetS/AAND during puberty, menopause, and old age.
Ishimitsu, T; Ono, H; Ogawa, Y; Tsukada, H; Oka, K; Yagi, S
To compare the protective effect against cardiac and renal damage of a beta-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats. Six-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks. Control (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate. These findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.
Sporková, Alexandra; Čertíková Chábová, Věra; Doleželová, Šárka; Jíchová, Šárka; Kopkan, Libor; Vaňourková, Zdeňka; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Maxová, Hana; Červenka, Luděk
There is vast evidence that the renin-angiotensin system is not the sole determinant of blood pressure (BP) elevation in human renovascular hypertension or the relevant experimental models. This study tested the hypothesis that kidney deficiency of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension. In 2K1C Goldblatt rats with established hypertension, angiotensin II, angiotensin 1-7, 20-HETE concentrations and gene expression of CYP4A1 enzyme (responsible for 20-HETE formation) of the nonclipped kidney were determined. We examined if 14 days׳ administration of fenofibrate, a lipid-lowering drug, would increase CYP4A1 gene expression and renal 20-HETE formation, and if increased 20-HETE concentrations in the nonclipped kidney would decrease BP (telemetric measurements). CYP4A1 gene expression, 20-HETE and angiotensin 1-7 concentrations were lower and angiotensin II levels were higher in the nonclipped kidney of 2K1C rats than in sham-operated rats. Fenofibrate increased CYP4A1 gene expression and 20-HETE concentration in the nonclipped kidney and significantly decreased BP in 2K1C rats but did not restore it to normotensive range. The treatment did not change BP in sham-operated rats. Our results suggest that alterations in the RAS and CYP-dependent ω-hydroxylase metabolites of arachidonic acid in the nonclipped kidneys are both important in the pathophysiology of the maintenance phase of 2K1C Goldblatt hypertension. Therefore, fenofibrate treatment effectively attenuated hypertension, probably via stimulation of 20-HETE formation in the nonclipped kidney. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
Marina, Nephtali; Ang, Richard; Machhada, Asif; Kasymov, Vitaliy; Karagiannis, Anastassios; Hosford, Patrick S; Mosienko, Valentina; Teschemacher, Anja G; Vihko, Pirkko; Paton, Julian F R; Kasparov, Sergey; Gourine, Alexander V
Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure. © 2015 The Authors.
Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R
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.
Perusquía, Mercedes; Herrera, Nieves; Ferrer, Mercedes; Stallone, John N
Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic, indwelling catheters were implanted in carotid artery and jugular vein of 18-21-week-old male spontaneously hypertensive rats (SHR) and normotensive-control Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively. Bolus injections of TES, 5α- or 5β-dihydrotestosterone (5α- and 5β-DHT), were administrated cumulatively to conscious rats at doses of 0.1-100μmolkg(-1)min(-1). 5β-DHT was also administrated during the pressor effect of Bay K 8644, an L-type voltage-operated Ca(2+) channel (L-VOCC) agonist. In separate experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail-cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent manner, while heart rate was reduced with some androgens at the highest doses. The hypotensive effects of androgens were markedly greater in SHR, with a rank order potency of: 5β-DHT>TES>5α-DHT. 5β-DHT, the most potent antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR. TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats, but this hypertension was prevented by TES replacement therapy. BP responses to androgens are androgen structure
Scholey, J W; Meyer, T W
Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy. PMID:2649514
Sovari, Ali A.; Pezhouman, Arash; Iyer, Shankar; Cao, Hong; Ko, Christopher Y.; Bapat, Aneesh; Vahdani, Nooshin; Ghanim, Mostafa; Fishbein, Michael C.
Key points Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias. Abstract Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H2O2; 0.15 mmol l−1). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H2O2 promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H2O2‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR
Kaiman, K; Shibata, S
After cold storage treatment (5-7 days at 2 degrees C) the sensitivity to norepinephrine (NE) was increased in rabbit portal vein, decreased in rat portal vein and not altered in guinea pig portal vein. Cold storage decreased the sensitivity to methoxamine (ME), Ba++ and Ca++ in rat and guinea pig veins but not in rabbit veins and failed to alter the sensitivity to K+ in all veins tested. Cold storage increased 45Ca-influx while it reduced the NE content and 3H-NE uptake of all portal veins examined. NE and ME-induced 45Ca-influx was greater in cold-stored veins that in fresh veins from rabbit and guinea pig. K+ decreased 45Ca-influx in all cold-stored veins. These results indicate that cold storage induces a prejunctional supersensitivity in rabbit portal vein but not in guinea pig and rat portal veins. However, cold storage increased 45Ca-influx in all three veins.
Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L
Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.
Oishi, J C; De Moraes, T F; Buzinari, T C; Cárnio, E C; Parizotto, N A; Rodrigues, G J
The purpose of this study was to evaluate the acute effect of photobiomodulation therapy (PBM) on arterial pressure in hypertensive and normotensive rats with application in an abdominal region. Normotensive (2K) and hypertensive (2K-1C) wistar rats were treated with PBM. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after PBM application. The nitric oxide (NO) serum concentration was measured before and after PBM application. Vascular reactivity study was performed in isolated thoracic aortas. Aluminum gallium arsenide (GaAlAs) diode laser was used, at 660nm wavelength and 100mW optical output. The PBM application induced a decrease of SAP in 2K-1C rats. In 2K rats, the PBM application had no effect on SAP, DAP and MAP. Moreover, the magnitude of hypotensive effect was higher in 2K-1C than in 2K rats. The PBM application induced a decrease of HR in 2K-1C and 2K, with higher effect in 2K-1C rats. In 2K-1C, the hypotensive effect induced by PBM was longer than that obtained in 2K rats. PBM application induced an elevation of NO concentration in serum from 2K-1C and 2K rats, with higher effect in 2K-1C. In isolated aortic rings PBM effect is dependent of NO release, and is not dependent of nitric oxide synthase (NOS) activation. Our results indicate that the abdominal acute application of PBM at 660nm is able to induce a long lasting hypotensive effect in hypertensive rats and vasodilation by a NO dependent mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.
Heloury, Y; Valayer, J; Hay, J M; Gauthier, F; Alagille, D
88 porto systemic shunts were performed between 1977-1985; 14 failures were observed. These failures occurred in ten children with extra-hepatic portal obstruction and in four with intra-hepatic obstruction. The treatment of these failures was different in these two groups: 7 reoperations in the extra-hepatic obstruction, none in the intra-hepatic. That reoperation is often not suitable in the intrahepatic obstruction because of the hepatic failure. The use of sclerotherapy or the beta receptor blocking agents is discussed in this group.
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
Buzueva, I I; Filjushina, E E; Shmerling, M D; Markel, A L; Jakobson, G S
The structure of zona reticularis of the adrenal cortex in hypertensive NISAG rats was studied during the early, middle, and late periods of postnatal ontogeny. The detected morphological signs suggest that hypotrophic changes in zona reticularis of the adrenal cortex in hypertensive rats appeared before the onset of high blood pressure and accompanied the development of arterial hypertension in these animals.
Markov, Kh M; Petrichuk, S V; Zavrieva, M K; Suslova, G F; Nartsissov, R P
The effect of varying magnetic field on the development of spontaneous hypertension was studied in experiments on Okamoto rats. The influence of magnetic field during antenatal development caused persistent changes in lymphocyte and organ metabolism and accelerated the appearance of spontaneous hypertension in rats. Based on enzymatic activity of lymphocytes it is possible to predict the development of spontaneous arterial hypertension.
Rossoni, Luciana V; Oliveira, Raphael A F; Caffaro, Rene R; Miana, Maria; Sanz-Rosa, David; Koike, Márcia K; Do Amaral, Sandra L; Michelini, Lisete C; Lahera, Vicente; Cachofeiro, Victoria
To evaluate the effect of low-intensity chronic exercise training (ExT) on blood pressure (BP), as well as the cardiac alterations associated with hypertension in aging hypertensive rats. Male spontaneously hypertensive rats (SHR; 21 months old) and their normotensive control Wistar-Kyoto (WKY) rats were submitted to low-intensity training protocol for 13 weeks. BP, cardiac morphological and morphometric analysis, as well as gene expression of fibrotic and inflammatory factors were analyzed at the end of the training period. ExT reduced BP and heart rate in aged SHR. Left ventricle hypertrophy, collagen volume fraction and wall-to-lumen ratio of myocardium arterioles were also decreased in trained SHR. However, ExT was unable to reverse the either reduced capillary density or the cardiac myocyte hypertrophy observed in SHR as compared with WKY rats. Trained SHR showed higher metalloproteinase-2/tissue inhibitor metalloproteinase-2 (MMP-2/TIMP-2) ratio and lower levels of α-smooth muscle actin, but similar levels of connective tissue growth factor, transforming growth factor beta or IL-1 beta to that of nontrained SHR. Low to moderate-intensity chronic ExT reverses the cardiac alterations associated with hypertension: myocardial arteriole, left ventricle hypertrophy, collagen content and tachycardia. These changes could be consequence or cause of the reduction in BP observed in trained SHR. In addition, ExT does not worsen the underlying inflammatory burden associated with hypertension. Therefore, the data support a beneficial effect of ExT in aging SHR similar to that reported in young or middle-aged individuals, confirming that exercise is a healthy habit that induces cardiac improvements independently of age.
Vu, Hop; Ianosi-Irimie, Monica; Danchuk, Svitlana; Rabon, Edd; Nogawa, Toshihiko; Kamano, Yoshiaki; Pettit, G Robert; Wiese, Thomas; Puschett, Jules B
The study of the pathogenesis of preeclampsia has been hampered by a relative dearth of animal models. We developed a rat model of preeclampsia in which the excretion of a circulating inhibitor of Na/K ATPase, marinobufagenin (MBG), is elevated. These animals develop hypertension, proteinuria, and intrauterine growth restriction. The administration of a congener of MBG, resibufogenin (RBG), reduces blood pressure to normal in these animals, as is the case when given to pregnant animals rendered hypertensive by the administration of MBG. Studies of Na/K ATPase inhibition by MBG and RBG reveal that these agents are equally effective as inhibitors of the enzyme.
Kumar, Ashish; Khan, Noor Muhammad; Anikhindi, Shrihari Anil; Sharma, Praveen; Bansal, Naresh; Singla, Vikas; Arora, Anil
AIM To study the diagnostic accuracy of transient elastography (TE) for detecting clinically significant portal hypertension (CSPH) in Indian patients with cirrhotic portal hypertension. METHODS This retrospective study was conducted at the Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, on consecutive patients with cirrhosis greater than 15 years of age who underwent hepatic venous pressure gradient (HVPG) and TE from July 2011 to May 2016. Correlation between HVPG and TE was analyzed using the Spearman’s correlation test. Receiver operating characteristic (ROC) curves were prepared for determining the utility of TE in predicting various stages of portal hypertension. The best cut-off value of TE for the diagnosis of CSPH was obtained using the Youden index. RESULTS The study included 326 patients [median age 52 (range 16-90) years; 81% males]. The most common etiology of cirrhosis was cryptogenic (45%) followed by alcohol (34%). The median HVPG was 16.0 (range 1.5 to 30.5) mmHg. Eighty-five percent of patients had CSPH. A significant positive correlation was noted between TE and HVPG (rho 0.361, P < 0.001). The area under ROC curve for TE in predicting CSPH was 0.740 (95%CI: 0.662-0.818) (P < 0.01). A cut-off value of TE of 21.6 kPa best predicted CSPH with a positive predictive value (PPV) of 93%. CONCLUSION TE has a fair positive correlation with HVPG; thus, TE can be used as a non-invasive modality to assess the degree of portal hypertension. A cut-off TE value of 21.6 kPa identifies CSPH with a PPV of 93%. PMID:28216976
Rajoriya, Neil; Tripathi, Dhiraj; Leithead, Joanna A; Gunson, Bridget K; Lord, Sophie; Ferguson, James W; Hirschfield, Gideon M
AIM To establish the impact of portal hypertension (PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease (PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters: (1) presence of radiological or endoscopic documented varices from our own centre or the referral centre; (2) splenomegaly (> 11 cm) on radiology in absence of splenic cysts accounting for increased imaging size; (3) thrombocytopenia (platelets < 150 × 109/L); or (4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients (F: M = 42: 5) were listed for liver transplantation (LT) (single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients (40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age (PH group, 50.6 (6.4); non-PH group, 47.1 (7.4) years; P = 0.101), median listing MELD (PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score (PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy (P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay (PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length (PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy (PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity. PMID:28018103
Williamson, M P; Behme, M T; Dupré, J; Grant, D R; Guan, J; Zhong, R
To compare the metabolic effects of portal and systemic delivery of insulin, we used portal-caval transposition (PCT) in rats to provide total systemic diversion of splanchnic venous blood. PCT rats exhibited normal weight gain, liver histology, liver-function tests, glycosylated hemoglobin, arterial blood pressure, and hepatic blood flow. Mean liver weight relative to body weight was 12% lower in PCT rats than in sham-operated control (CTR) rats 30 days following transposition. Indwelling venous catheters were established to facilitate metabolic studies in conscious, minimally restrained animals. Postabsorptive plasma glucose and C-peptide (CPEP) levels were similar in PCT and CTR rats; however, postabsorptive immunoreactive insulin (IRI) levels were elevated in PCT rats (67 +/- 3.1 v 49 +/- 3.5 pmol.L-1, P < .002, n = 11 v 11), as were postabsorptive plasma glucagon levels (570 +/- 67 v 240 +/- 11 ng.L-1, P < .001, n = 11 v 16) at similar body weights. The postabsorptive CPEP/IRI concentration ratio was lower in PCT than in CTR rats (4.0 +/- 0.3 v 6.0 +/- 0.6, P < .02), suggesting reduced hepatic extraction of insulin. Insulin sensitivity (IS), determined by minimal model analysis of frequently sampled intravenous glucose tolerance tests yielding the sensitivity index (SI), was reduced in PCT compared with CTR (61 +/- 5.6 v 86 +/- 9.0 (mumol.L-1)-1.min-1, P < .04, n = 9 v 10). During euglycemic-hyperinsulinemic clamps, glucose infusion rates (GIRs) from 60 to 120 minutes were lower in PCT than in CTR rats (6.0 +/- 0.3 v 8.0 +/- 0.4 g.kg-1.min-1, P < .002, n = 9 v 7) with matching plasma IRI levels, confirming the reduced IS in PCT rats. Areas under the concentration curves ([AUCs] 0 to 150 minutes) for glucose tolerance tests (gavage) indicated that plasma glucose excursion was similar in PCT and CTR rats whereas AUC IRI was significantly higher in PCT than in CTR rats (23 +/- 1.3 v 18 +/- 0.6 nmol.L-1.min, P < .009, n = 11 v 11). However, AUC CPEP for oral
Lorente, Laureano; Aller, Maria Angeles; Ispizua, José Ignacio; Rodriguez, José; Durán, Hipólito
One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to the host liver (PR), paraesophageal veins (PE) and splenorenal veins (SR). At 60 days P.T., PR and SR veins but not PE ones appeared, and at 30 days P.T., there were only PR veins. Graft atrophy at 90 days P.T. was associated with a severe degree of bile duct proliferation. The gradual development of portal hypertension causes porto-systemic collateral circulation and the graft loses the portal hepatotrophic factors. The late development of the portal hypertension and the biliary proliferation could be caused by the hepatic arterial ischemia in this experimental model. Thus, as has been described in the orthotopic liver tansplantation, the heterotopic one might require a double vascularization, both portal and arterial. PMID:2278927
Confalonieri, F; Ballerini, A; Santangelo, A; Turra, G
Cholecystolithotomy and cholecystojejunostomy has been carried out on 11 patients with severe hypertension from cirrhosis. The indications were frequently recurring attacks of biliary cholic or acute cholecystitis at onset. There was 1 postoperative death from cardiac infarction and only minor in-hospital morbidity. None of the remaining patients has to date developed post-cholecystojejunostomy sequelae. Except the case of extensive inflammation on gangrena, this procedure appears to be a safe and definitive operation, alternative to subtotal cholecystectomy.
Marshall, I.; Burt, R. P.; Green, G. M.; Hussain, M. B.; Chapple, C. R.
1. The alpha 1-adrenoceptor subtype mediating contraction of the rat hepatic portal vein to phenylephrine was characterized by use of competitive antagonists previously shown to have selectivity between the expressed alpha 1-subtype clones. Prazosin competitively antagonized the phenylephrine contractions with a pA2 value of 9.2, as did WB 4101 (pA2 9.4), 5-methyl urapidil (pA2 8.6), indoramin (pA2 8.4) and BMY 7378 (pA2 6.5). 2. The pA2 values on the rat portal vein correlated highly with their previously published pA2 values for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens and human prostate and poorly with those for the alpha 1B- and alpha 1D-adrenoceptors mediating contraction of the rat spleen and aorta, respectively. The antagonist pA2 values on the rat portal vein correlated highly with their previously published pK1 values for the expressed alpha 1a-clone and poorly with those for the expressed alpha 1b- and alpha 1d-clones. Therefore the results show that contraction of the rat portal vein to phenylephrine is mediated by alpha 1A-adrenoceptors. 3. The novel alpha 1-adrenoceptor antagonist RS 17053 had a relatively high affinity for the alpha 1A-adrenoceptors mediating contraction of the rat epididymal vas deferens (pA2 9.5) compared with the alpha 1B-adrenoceptors in the rat spleen (pA2 7.2) or the alpha 1D-adrenoceptors in the rat aorta (pKB 7.1), in agreement with its selectivity for the expressed alpha 1a-clone. However, RS 17053 had over 100 fold lower affinity for the alpha 1A-adrenoceptors mediating contraction of the rat portal vein (pKB 7.1) and human prostate (pKB 7.1) compared with its affinity for the alpha 1A-adrenoceptors in the rat epididymal vas deferens or the expressed alpha 1a-clone. 4. The difference in affinity of RS 17053 between the rat epididymal vas deferens and rat portal vein cannot be explained by a species difference in the receptor. Therefore RS 17053 may distinguish between subtypes of
Victery, W.; Vander, A.J.; Shulak, J.M.; Schoeps, P.; Julius, S.
Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 100, or 500 ppm Pb (as Pb acetate) and then continuing this regimen after weaning. Male rats receiving 100 ppm developed a significant elevation of systolic blood pressure (152 +/- 3.7 mm Hg vs. 135 +/- 5.6 for controls) at 3 1/2 months and remained hypertensive until sacrifice at 6 months; 500 ppm rats remained normotensive. Both 100 ppm and 500 ppm females remained normotensive. At 6 months plasma renin activity (PRA) was significantly reduced in the 100 ppm male group but was normal in the 500 ppm group. There was dose-dependent decreases in the All/PRA ratio and in renal renin. Pulmonary converting enzyme activity was not changed by Pb exposure. Blood (Pb) was 40 and 71 ..mu..g/dl, respectively, and kidney (Pb) was 4.8 and 22.9 ..mu..g/gm. Renal histology was normal in the 100 ppm group. We conclude that doses of Pb which produce blood (Pb) seen in many people are capable of including modest hypertension in male rats; higher doses fail to do so. The hypertension is associated with a reduction in PRA and All and therefore is unlikely to be due to hyperactivity of the renin-angiotensin system (RAS).
Harwani, Sailesh C; Ratcliff, Jason; Sutterwala, Fayyaz S; Ballas, Zuhair K; Meyerholz, David K; Chapleau, Mark W; Abboud, Francois M
Renal inflammation contributes to the pathophysiology of hypertension. CD161a(+) immune cells are dominant in the (SHR) spontaneously hypertensive rat and expand in response to nicotinic cholinergic activation. We aimed to phenotype CD161a(+) immune cells in prehypertensive SHR after cholinergic activation with nicotine and determine if these cells are involved in renal inflammation and the development of hypertension. Studies used young SHR and WKY (Wistar-Kyoto) rats. Splenocytes and bone marrow cells were exposed to nicotine ex vivo, and nicotine was infused in vivo. Blood pressures, kidney, serum, and urine were obtained. Flow cytometry, Luminex/ELISA, immunohistochemistry, confocal microscopy, and Western blot were used. Nicotinic cholinergic activation induced proliferation of CD161a(+)/CD68(+) macrophages in SHR-derived splenocytes, their renal infiltration, and premature hypertension in SHR. These changes were associated with increased renal expression of MCP-1 (monocyte chemoattractant protein-1) and VLA-4 (very-late antigen-4). LLT1 (lectin-like transcript 1), the ligand for CD161a, was overexpressed in SHR kidney, whereas vascular cellular and intracellular adhesion molecules were similar to those in WKY. Inflammatory cytokines were elevated in SHR kidney and urine after nicotine infusion. Nicotine-mediated renal macrophage infiltration/inflammation was enhanced in denervated kidneys, not explained by angiotensin II levels or expression of angiotensin type-1/2 receptors. Moreover, expression of the anti-inflammatory α7-nAChR (α7-nicotinic acetylcholine receptor) was similar in young SHR and WKY rats. A novel, inherited nicotinic cholinergic inflammatory effect exists in young SHR, measured by expansion of CD161a(+)/CD68(+) macrophages. This leads to renal inflammation and premature hypertension, which may be partially explained by increased renal expression of LLT-1, MCP-1, and VLA-4. © 2016 American Heart Association, Inc.
Farnham, M M J; Lung, M S Y; Tallapragada, V J; Pilowsky, P M
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide that plays an important role in hypertension and stress responses. PACAP acts at three G protein-coupled receptors [PACAP type 1 receptor (PAC(1)) and vasoactive intestinal peptide receptor types 1 and 2 (VPAC(1) and VPAC(2))] and is localized to sites involved in cardiovascular control, most significantly the rostral ventrolateral medulla (RVLM). The RVLM is crucial for the tonic and reflex control of efferent sympathetic activity. Increases in sympathetic activity are observed in most types of hypertension and heart failure. PACAP delivered intrathecally also causes massive sympathoexcitation. We aimed to determine the presence and abundance of the three PACAP receptors in the RVLM, the role, in vivo, of PACAP in the RVLM on tonic and reflex cardiovascular control, and the contribution of PACAP to hypertension in the spontaneously hypertensive rat (SHR). Data were obtained using quantitative PCR and microinjection of PACAP and its antagonist, PACAP(6-38), into the RVLM of anesthetized artificially ventilated normotensive rats or SHRs. All three receptors were present in the RVLM. PACAP microinjection into the RVLM caused sustained sympathoexcitation and tachycardia with a transient hypertension but did not affect homeostatic reflexes. The responses were partially mediated through PAC(1)/VPAC(2) receptors since the effect of PACAP was attenuated (∼50%) by PACAP(6-38). PACAP was not tonically active in the RVLM in this preparation because PACAP(6-38) on its own had no inhibitory effect. PACAP has long-lasting cardiovascular effects, but altered PACAP signaling within the RVLM is not a cause of hypertension in the SHR.
Ren, Xing-Sheng; Ling, Li; Zhou, Bing; Han, Ying; Zhou, Ye-Bo; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing
Salusin-β is a bioactive peptide involved in vascular smooth muscle cell proliferation, vascular fibrosis and hypertension. The present study was designed to determine the effects of silencing salusin-β on hypertension and cardiovascular remodeling in spontaneously hypertensive rats (SHR). Thirteen-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were subjected to intravenous injection of PBS, adenoviral vectors encoding salusin-β shRNA (Ad-Sal-shRNA) or a scramble shRNA. Salusin-β levels in plasma, myocardium and mesenteric artery were increased in SHR. Silencing salusin-β had no significant effect on blood pressure in WKY, but reduced blood pressure in SHR. It reduced the ratio of left ventricle weight to body weight, cross-sectional areas of cardiocytes and perivascular fibrosis, and decreased the media thickness and the media/lumen ratio of arteries in SHR. Silencing salusin-β almost normalized plasma norepinephrine and angiotensin II levels in SHR. It prevented the upregulation of angiotensin II and AT1 receptors, and reduced the NAD(P)H oxidase activity and superoxide anion levels in myocardium and mesenteric artery of SHR. Knockdown of salusin-β attenuated cell proliferation and fibrosis in vascular smooth muscle cells from SHR. These results indicate that silencing salusin-β attenuates hypertension and cardiovascular remodeling in SHR. PMID:28230187
Shechtman, O; Fregly, M J; Papanek, P E
A 3- to 4-week exposure of rats to a cold environment (5 +/- 2 degrees C) induces hypertension, including elevation of systolic, diastolic, and mean blood pressures and cardiac (left ventricular) hypertrophy. The studies described here were designed to investigate some factors affecting both the magnitude and the time course for development of cold-induced hypertension. The objective of the first study was to determine whether there was an ambient temperature at which the cold-induced elevation of blood pressure did not occur. The objective of the second experiment was to determine whether body weight at the time of exposure to cold affected the magnitude and time course for development of hypertension. To assess the first objective, male rats were housed in a chamber whose temperature was maintained at 5 +/- 2 degrees C while others were housed in an identical chamber at 9 +/- 2 degrees C. After 7 days of exposure to cold, the rats exposed to the colder temperature had a significant elevation of blood pressure (140 +/- 2 mm Hg) compared with the group maintained at 9 degrees C (122 +/- 3 mm Hg). The rats exposed to 9 degrees C had no significant elevation of systolic blood pressure at either 27 or 40 days after initiation of exposure to cold. At the latter time, the temperature in the second chamber was reduced to 5 +/- 2 degrees C. By the 25th day of exposure to this ambient temperature, the rats had a significant increase in systolic blood pressure above their levels at 9 degrees C. Thus, there appears to be a threshold ambient temperature for elevation of blood pressure during exposure to cold. That temperature appears to lie somewhere between 5 and 9 degrees C. The second objective was assessed by placing rats varying in weight from approximately 250 to 430 g in air at 5 degrees C. There was a highly significant direct relationship (r = 0.96) between body weight at the time of introduction to cold and the number of days required to increase systolic blood
Kalaivani, Periyathambi; Saranya, Ramesh Babu; Ramakrishnan, Ganapathy; Ranju, Vijayan; Sathiya, Sekar; Gayathri, Veeraraghavan; Thiyagarajan, Lakshmi Kantham; Venkhatesh, Jayakothanda Ramaswamy; Babu, Chidambaram Saravana; Thanikachalam, Sadagopan
Cuminum cyminum (CC) is a commonly used spice in South Indian foods. It has been traditionally used for the treatment and management of sleep disorders, indigestion, and hypertension. The present study was carried out to scientifically evaluate the anti-hypertensive potential of standardized aqueous extract of CC seeds and its role in arterial endothelial nitric oxide synthase expression, inflammation, and oxidative stress in renal hypertensive rats. Renal hypertension was induced by the two-kidney one-clip (2K/1C) method in rats. Systolic blood pressure (SBP), plasma nitrate/nitrite, carotid-eNOS, renal-TNF-α, IL-6, Bax, Bcl-2, thioredoxin 1 (TRX1), and thioredoxin reductase 1 (TRXR1) mRNA expressions were studied to demonstrate the anti-hypertensive action of CC. Cuminum cyminum was administered orally (200 mg/kg b.wt) for a period of 9 weeks; it improved plasma nitric oxide and decreased the systolic blood pressure in hypertensive rats. It also up-regulated the gene expression of eNOS, Bcl-2, TRX1, and TRXR1; and down-regulated Bax, TNF-α, and IL-6. These data reveal that CC seeds augment endothelial functions and ameliorate inflammatory and oxidative stress in hypertensive rats. The present report is the first of its kind to demonstrate the mechanism of anti-hypertensive action of CC seeds in an animal model of renovascular hypertension.
The effects of L-propionylcarnitine (LPC) on spontaneous mechanical and electrical activity of rat portal vein have been studied "in vitro" by means of an isometric technique. Mechanical activity in normal Krebs solution consisted, in the majority of cases, in phasic contractions with variable amplitude, duration and frequency, while electrical activity showed both slow and fast spike potential components. By adding LPC to the medium at doses ranging from 10(-5) M to 10(-3) M, no effect has been observed while at concentrations from 2 x 10(-3) M to 8 x 10(-3) M, after an initial period of total inhibition, a dose-dependent increase in amplitude associated with a parallel decrease in frequency of contraction waves have been observed. The pattern of electrical activity was characterized by a regular slow wave component with the same frequency of the mechanical waves, and by an increase in number, amplitude and frequency of spike potentials. Experiments on synchronization of contractile activity showed that, in presence of LPC, hepatic and mesenteric regions of the vessel contract in close synchronism. These results suggest that LPC synchronizes spontaneous activity of rat portal vein by means of a mechanism which is at the present unknown.
Zsoter, T.T.; Wolchinsky, C.; Lawrin, M.; Sirko, S.
The role of the sympathetic nervous system in arterial hypertension cannot be properly evaluated until it is known about the activity in the vessels themselves. In this study researchers investigated the effect of transmural stimulation on the tail artery - labelled in vitro with /sup 3/H-norepinephrine - of 7-9 week old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKR). Electrical stimulation using two frequencies (2 and 10 Hz) resulted in significantly more /sup 3/H overflow in vessels from SHR than from WKR. With 10 Hz stimulation the fractional release was also greater. Column chromatographic analysis of /sup 3/H overflow revealed that transmural stimulation in arteries of SHR enhanced mainly the release of norepinephrine and not of its metabolites. Significantly, an increased release of /sup 3/H-norepinephrine on stimulation was observed in SHR before the full development of hypertension suggesting that it might be a cause rather than a consequence of high blood pressure.
Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G
Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.
Roysommuti, Sanya; Mozaffari, Mahmood S; Wyss, J Michael
Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin-angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.
Wang, Qi Xiong, Bin Zheng, ChuanSheng Liang, Ming Han, Ping
ObjectiveThis retrospective study reports our experience using splenic arterial particle embolization and coil embolization for the treatment of sinistral portal hypertension (SPH) in patients with and without gastric bleeding.MethodsFrom August 2009 to May 2012, 14 patients with SPH due to pancreatic disease were diagnosed and treated with splenic arterial embolization. Two different embolization strategies were applied; either combined distal splenic bed particle embolization and proximal splenic artery coil embolization in the same procedure for acute hemorrhage (1-step) or interval staged distal embolization and proximal embolization in the stable patient (2-step). The patients were clinically followed.ResultsIn 14 patients, splenic arterial embolization was successful. The one-step method was performed in three patients suffering from massive gastric bleeding, and the bleeding was relieved after embolization. The two-step method was used in 11 patients, who had chronic gastric variceal bleeding or gastric varices only. The gastric varices disappeared in the enhanced CT scan and the patients had no gastric bleeding during follow-up.ConclusionsSplenic arterial embolization, particularly the two-step method, proved feasible and effective for the treatment of SPH patients with gastric varices or gastric variceal bleeding.
Bertoli, Luigi F; Lee, Pauline L; Lallone, Lauren; Barton, James C
Intravenous bevacizumab decreased mucosal bleeding in some patients with hereditary hemorrhagic telangiectasia (HHT). We treated a 47-year-old male who had HHT, severe epistaxis, and gastrointestinal bleeding, alcoholic cirrhosis, and portal hypertension with intravenous bevacizumab 2.5 mg/kg every 2 weeks. We tabulated these measures weekly during weeks 1-33 (no bevacizumab); 34-57 (bevacizumab); and 58-97 (no bevacizumab): hemoglobin (Hb) levels; platelet counts; units of transfused packed erythrocytes (PRBC units); and quantities of iron infused as iron dextran to support erythropoiesis. We performed univariate and multivariable analyses. We sequenced his ENG and ACVRL1 genes. Epistaxis and melena decreased markedly during bevacizumab treatment. He reported no adverse effects due to bevacizumab. Mean weekly Hb levels were significantly higher and mean weekly PRBC units and quantities of intravenous iron were significantly lower during bevacizumab treatment. We performed a multiple regression on weekly Hb levels using these independent variables: bevacizumab treatment (dichotomous); weekly platelet counts; weekly PRBC units; and weekly quantities of intravenous iron. There was 1 positive association: (bevacizumab treatment; p = 0.0046) and 1 negative association (PRBC units; p = 0.0004). This patient had the novel ENG mutation E137K (exon 4; c.409G→A). Intravenous bevacizumab treatment 2.5 mg/kg every 2 weeks for 24 weeks was well-tolerated by a patient with HHT due to ENG E137K and was associated with higher weekly Hb levels and fewer weekly PRBC units.
Van Steenkiste, Christophe; Ribera, Jordi; Geerts, Anja; Pauta, Montse; Tugues, Sònia; Casteleyn, Christophe; Libbrecht, Louis; Olievier, Kim; Schroyen, Ben; Reynaert, Hendrik; van Grunsven, Leo A; Blomme, Bram; Coulon, Stephanie; Heindryckx, Femke; De Vos, Martine; Stassen, Jean Marie; Vinckier, Stefan; Altamirano, Jose; Bataller, Ramón; Carmeliet, Peter; Van Vlierberghe, Hans; Colle, Isabelle; Morales-Ruiz, Manuel
Placental growth factor (PlGF) is associated selectively with pathological angiogenesis, and PlGF blockade does not affect the healthy vasculature. Anti-PlGF is therefore currently being clinically evaluated for the treatment of cancer patients. In cirrhosis, hepatic fibrogenesis is accompanied by extensive angiogenesis. In this paper, we evaluated the pathophysiological role of PlGF and the therapeutic potential of anti-PlGF in liver cirrhosis. PlGF was significantly up-regulated in the CCl(4) -induced rodent model of liver cirrhosis as well as in cirrhotic patients. Compared with wild-type animals, cirrhotic PlGF(-/-) mice showed a significant reduction in angiogenesis, arteriogenesis, inflammation, fibrosis, and portal hypertension. Importantly, pharmacological inhibition with anti-PlGF antibodies yielded similar results as genetic loss of PlGF. Notably, PlGF treatment of activated hepatic stellate cells induced sustained extracellular signal-regulated kinase 1/2 phosphorylation, as well as chemotaxis and proliferation, indicating a previously unrecognized profibrogenic role of PlGF. PlGF is a disease-candidate gene in liver cirrhosis, and inhibition of PlGF offers a therapeutic alternative with an attractive safety profile. Copyright © 2011 American Association for the Study of Liver Diseases.
Kim, Gaeun; Kim, Moon Young; Baik, Soon Koo
Background/Aims Transient elastography (TE) has been proposed as a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for detecting portal hypertension (PH). However, previous studies have yielded conflicting results. We gathered evidence from literature on the clinical usefulness of TE versus HVPG for assessing PH. Methods We conducted a systematic review by searching databases for relevant literature evaluating the clinical usefulness of non-invasive TE for assessing PH in patients with cirrhosis. A literature search in Ovid Medline, EMBASE and the Cochrane Library was performed for all studies published prior to December 30, 2015. Results Eight studies (1,356 patients) met our inclusion criteria. For the detection of PH (HVPG ≥6 mmHg), the summary sensitivity and specificity were 0.88 (95% confidence interval [CI] 0.86-0.90) and 0.74 (95% CI 0.67-0.81), respectively. Regarding clinically significant PH (HVPG ≥10 mmHg), the summary sensitivity and specificity were 0.85 (95% CI 0.63-0.97) and 0.71 (95% CI 0.50-0.93), respectively. The overall correlation estimate of TE and HVPG was large (0.75, 95% CI: 0.65; 0.82, P<0.0001). Conclusions TE showed high accuracy and correlation for detecting the severity of PH. Therefore, TE shows promise as a reliable and non-invasive procedure for the evaluation of PH that should be integrated into clinical practice. PMID:28263953
Chan, Vincent; Fenning, Andrew; Iyer, Abishek; Hoey, Andrew; Brown, Lindsay
The phytoalexin resveratrol (3,4',5-trihydroxy-trans-stilbene) may attenuate cardiovascular disease in man. This study has determined whether treatment with resveratrol (1 mg/kg/day orally) prevented cardiac fibrosis and the decreased cardiovascular function in the DOCA-salt hypertensive rat as a model of human hypertension. Uninephrectomised rats (UNX) administered DOCA (25mg every 4th day sc) and 1% NaCl in drinking water for 28 days developed cardiac and vascular remodelling. In these DOCA-salt rats, resveratrol decreased inflammatory cell infiltration, decreased cardiac fibrosis (left ventricular interstitial and perivascular collagen content) and improved cardiac and vascular function. Resveratrol attenuated other features of cardiovascular remodelling such as increases in systolic blood pressure, left ventricular wet weight, left ventricular wall thickness, diastolic stiffness constant, as well as decreased cardiac contractility and prolonged action potential duration characteristic of DOCA-salt rats. In summary, resveratrol, at a nutritionally relevant dose, prevents or attenuates the adverse changes in the cardiovascular system. We propose that the anti-inflammatory and anti-fibrotic effects of resveratrol are responsible, at least in part, for its amelioration in cardiovascular remodelling in DOCA-salt rats. These actions of resveratrol could play an important role in the protective effects on the human cardiovascular system reported for this constituent of red wine.
Moreno, Enrique; Moral-Sanz, Javier; Barreira, Bianca; Galindo, Pilar; Pandolfi, Rachele; Jimenez, Rosario; Moreno, Laura; Cogolludo, Angel; Duarte, Juan; Perez-Vizcaino, Francisco
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
Schyvens, Christopher G; Andrews, Miles C; Tam, Rachel; Mori, Trevor A; Croft, Kevin D; McKenzie, Katja U S; Whitworth, Judith A; Zhang, Yi
This study examined whether the anti-oxidants ascorbic acid, alpha- or gamma-tocopherol, could modify adrenocorticotrophic hormone (ACTH)-hypertension in Sprague-Dawley rats, a model associated with increased oxidative stress. Systolic blood pressure (SBP) was measured by the tail-cuff method. After four days of ascorbic acid (AA) (200 mg/kg/day drinking) or alpha-tocopherol (500 mg/kg/d i.p. or feed), rats were co-administered ACTH (0.2 mg/kg/day s.c.) or saline for 11 days (prevention studies). In reversal studies, ACTH/saline was administered for 15 days, and from day 9, alpha- or gamma-tocopherol (20 mg/kg/day) was added. ACTH increased SBP compared to saline (p < 0.05). AA or alpha-tocopherol failed to prevent and alpha- or gamma-tocopherol failed to reverse ACTH-induced hypertension. Thus, neither vitamin C (water soluble) nor E (lipid soluble) modified ACTH-induced hypertension in the rat.
Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L
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 (with L-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 with L-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 by L-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.
Shirakura, Takashi; Nomura, Johji; Matsui, Chieko; Kobayashi, Tsunefumi; Tamura, Mizuho; Masuzaki, Hiroaki
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.
Rodríguez-Iturbe, Bernardo; Ferrebuz, Atilio; Vanegas, Valentina; Quiroz, Yasmir; Mezzano, Sergio; Vaziri, Nosratola D
Compelling evidence has emerged pointing to the interaction of oxidative stress and renal interstitial inflammation and their mutual contribution to the pathogenesis of hypertension in experimental animals. Renal interstitial inflammation in spontaneously hypertensive rats (SHR) is accompanied by and largely due to activation of redox-sensitive, proinflammatory nuclear transcription factor-kappaB (NF-kappaB). Therefore, the present study was designed to test the hypothesis that long-term inhibition of NF-kappaB, beginning early in the course of the disease, may attenuate renal interstitial inflammation and hypertension in SHR. To this end, we administered the reputed NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) (100 mg/kg daily intraperitoneally) to SHR from 7 to 25 weeks of age and compared the results with vehicle-treated SHR. Vehicle-treated and PDTC-treated Wistar Kyoto (WKY) rats served as controls. The untreated SHR exhibited a significant rise in arterial pressure; increased NF-kappaB activation, elevated intercellular adhesion molecule (ICAM)-1 and in situ mRNA macrophage chemoattractant molecule-1 (MCP-1) expressions; and interstitial accumulation of lymphocytes, macrophages, and angiotensin-II-positive cells. PDTC administration prevented the rise in blood pressure, and normalized renal cortical NF-kappaB activity as well as ICAM-1 and MCP-1 expressions. This was accompanied by a significant reduction in infiltration of immune cells, angiotensin II-expressing cells, and renal tissue malondialdehyde content to values that matched those found in the control WKY rats. Results suggest that NF-kappaB-driven intrarenal inflammatory reactivity play a major role in the pathogenesis of hypertension in the SHR.
Keen, H L; Brands, M W; Smith, M J; Shek, E W; Hall, J E
Chronic insulin infusion in rats increases mean arterial pressure (MAP) and reduces glomerular filtration rate (GFR), but the mechanisms for these actions are not known. This study tested whether thromboxane synthesis inhibition (TSI) would attenuate the renal and blood pressure responses to sustained hyperinsulinemia. Male Sprague-Dawley rats were instrumented with arterial and venous catheters, and MAP was measured 24 h/day. After 4 days of baseline measurements, endogenous synthesis of thromboxane was suppressed in 7 rats by infusing the thromboxane synthetase inhibitor, U63557A, intravenously (30 microg/kg/min) for the remainder of the experiment; 7 other rats received vehicle. Baseline MAP was not significantly different between vehicle and TSI rats (96 +/- 1 v 99 +/- 1 mm Hg). After 3 days of U63557A or vehicle, a 5-day control period was started, followed by a 7-day infusion of insulin (1.5 mU/kg/min, intravenously). Glucose (22 mg/kg/min, intravenously) was infused along with insulin to prevent hypoglycemia. In the control period, MAP was not different between vehicle and TSI rats (99 +/- 2 v 100 +/- 1 mm Hg), but MAP increased throughout the 7-day infusion period only in the vehicle rats with an average increase in blood pressure of 7 +/- 2 mm Hg. In the control period, GFR was lower in vehicle rats compared with TSI rats (2.5 +/- 0.1 v 3.1 +/- 0.2 mL/min, P = .06), and the decrease to 81% +/- 4% and 91% +/- 6% of control, respectively, during insulin was significant only in the vehicle rats. All variables returned toward control during a 6-day recovery period. These results suggest that full expression of hypertension and renal vasoconstriction during hyperinsulinemia in rats is dependent on a normal ability to synthesize thromboxane.
D'Antiga, Lorenzo; Dacchille, Patrizia; Boniver, Clementina; Poledri, Sara; Schiff, Sami; Zancan, Lucia; Amodio, Piero
In children with noncirrhotic extrahepatic portal vein obstruction (EHPVO), minimal hepatic encephalopathy (MHE) was reported in a few series, but neither is it routinely investigated nor does consensus about its diagnosis exist. In this prospective observational study we aimed at detecting the prevalence of MHE in children with EHPVO and providing a practical diagnostic protocol. A consecutive sample of 13 noncirrhotic children (age range 4-18 years) with EHPVO underwent a screening for MHE based on level of fasting ammonia, quantified electroencephalogram (EEG) evaluation, and a wide battery of 26 psychometric tests exploring learning ability, abstract reasoning, phonemic and semantic fluency, selective attention, executive functions, short-term verbal and visual memory, long-term verbal memory, and visuopractic ability. Five children had at least 2 altered psychometric tests. Selective attention, executive function, and short-term visual memory were the domains more frequently altered, and 4 tests were enough to detect 80% of these children. Fasting ammonia plasma level was increased in 6 children. EEG mean dominant frequency adjusted for age was associated with serum ammonia concentration (β = -0.44 ± 0.19, P < 0.05). As a whole, children with EHPVO showed trends for lower α (median 41% vs 49%) and higher θ power than controls (median 41% vs 49% and 29% vs 20%, respectively). MHE affects approximately 50% of children with EHPVO and, therefore, is worthwhile to be investigated. Three simple tools, serum ammonia, quantified EEG, and neuropsychological examination, focused on selective attention, executive function, and short-term visual memory can be used effectively in the evaluation of MHE in this setting.
Schweizer, W; Duda, P; Tanner, S; Balsiger, D; Höflin, F; Zimmermann, A; Blumgart, L H
Patients with lobar or segmental, benign or malignant strictures of the biliary tree (with or without impairment of the portal blood flow) show a considerable atrophy of the involved area of the liver with a compensatory hypertrophy/hyperplasia of the remaining non affected liver. To investigate the importance of the biliary and portal obstruction for the development of this process, we used a rat model, with selective biliary and/or portal ligation of the anterior liver lobes (two thirds of the liver mass). Weight measurements, morphometry, functional scintigraphy (Hepatoiodida-scan) and blood enzyme analyses were done immediately postoperatively, at 30 hours and 4, 8 and 28 days after the operation. The major findings were: 1. 28 days after biliary and/or portal ligation there was no difference between the body weight of the four groups, all ligated animals having compensated for an initial greater percentage body-weight loss. 2. Total liver weight remained constant, while atrophy and hypertrophy/hyperplasia occurred although a progressive derangement of liver morphology was observed during that time. 3. A severe atrophy-hypertrophy-complex (AHC) developed after selective portal ligation, which in our experiment did not appear after selective biliary ligation. 4. Morphometrical changes after selective biliary ligation were reversible, whereas in liver lobes with selective portal ligation a progressive parenchymal destruction and involution with subsequent impairment of hepatic function of the concerned lobe was observed.
DeLano, F A; Balete, R; Schmid-Schönbein, G W
One mechanism for organ damage in individuals with arterial hypertension may be due to oxygen free radical production. This study was designed to localize free radicals in a microvascular network of mature spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Because glucocorticoids play a role in pressure elevation of SHRs, we investigated their role in microvascular free radical formation. Oxygen radical production in mesentery was detected by tetranitroblue tetrazolium reduction to formazan aided by digital light-absorption measurements. Formazan deposits were observed in the endothelial cells and lumens of all microvessels and in lymphatic endothelia but were fewer in tissue parenchyma. The formazan distribution in younger (14-16 wk old) WKY rats and SHRs was heterogeneous with low values in capillaries and small arterioles/venules (<30 microm) but enhanced deposits in larger venules. Adrenalectomy served to reduce the formazan density in SHRs to the level of WKY rats, whereas dexamethasone supplementation of the adrenalectomized rats caused elevation in the larger venules of SHRs. In older (40 wk old) SHRs, formazan levels were elevated in all hierarchies of microvessels. After pressure reduction was employed with chronic hydralazine treatment, the formazan deposits were reduced in all locations of the microcirculation in both WKY rats and SHRs. Elevated formazan deposits were also found in lymphatic endothelium. These results suggest that oxygen free radical production is elevated in both high- and low-pressure regions of SHR microcirculation via a process that is controlled by glucocorticoids. Older SHRs have higher formazan levels than younger SHRs in all microvessels. Chronic hydralazine treatment, which serves to reduce arterial blood pressure, attenuates tetranitroblue tetrazolium reduction in WKY rats and SHRs even in venules of the microcirculation, which has no micropressure elevation. Free radical production may be a more
Biancardi, V C; Bergamaschi, C T; Lopes, O U; Campos, R R
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.
Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J.; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert
ABSTRACT We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying
Zhang, Bing; He, Kunlun; Chen, Wei; Cheng, Xianfa; Cui, Hao; Zhong, Wu; Li, Song; Wang, Lili
Combining drugs with complementary mechanisms of action may contribute to improved hypertension control in diabetic patients. Advanced glycation end-product (AGE) breakers, a new class of candidate drugs targeting aging-related cardiovascular dysfunction, may be useful as novel adjuvant agents to improve the efficacy of diabetic hypertension (DH) treatment. This study evaluated the effects of alagebrium (ALT-711), an AGE breaker, combined with nifedipine, a Ca(2+) channel blocker, in a rat model of streptozotocin-induced DH. Compared with monotherapy, combination treatment significantly decreased systolic and diastolic blood pressure values, increased the pulse pressure, and decreased the coefficient of variation of the systolic blood pressure. Plasma biochemistry indicated that the concentrations of prostacyclin and nitric oxide were increased. Gene expression analysis showed significantly decreased prepro-endothelin-1expression in the aorta. These results reveal that alagebrium significantly improves the anti-hypertensive actions of nifedipine in a rat model of DH and suggest its potential use in the successful control of clinical DH.
Piotrowska, Ż; Janiuk, I; Lewandowska, A; Kasacka, I
Hypertension is one of the major endocrine and metabolic disorders, in which visfatin plays a significant role. The objective of this study was to evaluate the immunoreactivity of visfatin in pancreas and liver of two kidney, one clip (2K1C) renovascular hypertension model in rats. The studies were carried out on the pancreas and liver of rats. After a 6-week period of the renal artery clipping procedure, 2K1C rats developed a stable hypertension. Paraffin sections were stained with hematoxylin and eosin (for general histological examination) and processed for immunolocalization of visfatin. The intensity of immunohistochemical reaction was measured using Nikon NIS-Elements Advanced Research software. The hypertension significantly weakened the immunohistochemical reaction exhibiting visfatin in the pancreas and liver of hypertensive rats, compared to control animals. The changes induced by hypertension in the visfatin-containing cells in the pancreas and liver of the rats are discussed and needs further study.
Sun, Dongmei; Cheng, Yu; Zhou, Danfeng; Liu, Tanshu; Chen, Shaoqin; Liang, Jing; Tang, Chunzhi; Lai, Xinsheng
We performed an extensive quantitative proteomic analysis on the pooled medulla sample of the 11-week-old spontaneously hypertensive rats (SHR) compared to age-matched normotensive Wistar rats, using iTRAQ technology coupled with nano two-dimentional liquid chromatography followed by high resolution mass spectrometric abundance indexes techniques. Many differentially expressed proteins identified were involved in energy metabolism, such as mitochondrial part, pyruvate dehydrogenase complex, and respiratory chain. These proteins were included in citrate cycle (TCA cycle), pyruvate metabolism and oxidative phosphorylation. The proteomic analysis and subsequent Western blotting on two independent cohorts of animials indicated that the dysregulation of energy metabolism existed in the medulla of the SHR rats. The differentially expressed proteins in the dysregulation of energy metabolism in the medulla of SHR rats included down-regulated ATP6V1D, ATP6VOA1, ATP5L, DLD proteins and up-regulated AK1 protein. MAO-A protein also exhibited decreased regulation, as well as the other 3 above-mentioned energy-relative proteins (ATP6V1D, ATP5L and DLD proteins) belonging to the heterocycle metabolic process. A receiver operating characteristic curve (ROC) analysis on 4 of the differentially expressed proteins respectively resulted in an area under the receiver operating characteristic curve (AUC) of 0.95, 0.90, 0.92, and 0.81 for differentiating the SHR rats from the normotensive rats. This dysfunction in energy metabolism localizes to the medulla, the lower part of brain stem, and is, therefore, likely to contribute to the development, as well as to pathophysiological complications of hypertension.
Furedi, Nora; Miko, Alexandra; Aubrecht, Bianka; Gaszner, Balazs; Feller, Diana; Rostas, Ildiko; Tenk, Judit; Soos, Szilvia; Balasko, Marta; Balogh, Andras; Pap, Marianna; Petervari, Erika
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.
Yelamarty, R V; Moore, R L; Yu, F T; Elensky, M; Semanchick, A M; Cheung, J Y
In myocardial hypertrophy secondary to renovascular hypertension, the rate of intracellular Ca2+ concentration decline during relaxation in paced left ventricular (LV) myocytes isolated from hypertensive (Hyp) rats is much slower compared with that from normotensive (Sham) rats. By use of a novel liquid-crystal television-based optical-digital processor capable of performing on-line real-time Fourier transformation and the striated pattern (similar to 1-dimensional diffraction grating) of cardiac muscle cells, sarcomere shortening and relaxation velocities were measured in single Hyp and Sham myocytes 18 h after isolation. There were no differences in resting sarcomere length, percent of maximal shortening, time to peak shortening, and average sarcomere shortening velocity between Sham and Hyp cardiac cells. In contrast, average sarcomere relaxation velocity and half-relaxation time were significantly prolonged in Hyp myocytes. Contractile differences between Sham and Hyp myocytes detected by the optical-digital processor are confirmed by an independent method of video tracking of whole cell length changes during excitation-contraction. Despite the fact that freshly isolated myocytes contract more rigorously than 18-h-old myocytes, the relaxation abnormality was still observed in freshly isolated Hyp myocytes, suggesting impaired relaxation is an intrinsic property of Hyp myocytes rather than changes brought about by short-term culture. We postulate that reduced sarcomere relaxation velocity is a direct consequence of impaired Ca2+ sequestration-extrusion during relaxation in Hyp myocytes and may be responsible for diastolic dysfunction in hypertensive hypertrophic myocardium at the cellular level.
Caronna, Roberto; Bezzi, Mario; Schiratti, Monica; Cardi, Maurizio; Prezioso, Giampaolo; Benedetti, Michele; Papini, Federica; Mangioni, Simona; Martino, Gabriele; Chirletti, Piero
A non cirrhotic patient with esophageal varices and portal vein thrombosis had recurrent variceal bleeding unsuccessfully controlled by endoscopy and esophageal transection. Emergency transhepatic portography confirmed the thrombosed right branch of the portal vein, while the left branch appeared angulated, shifted and stenotic. A stent was successfully implanted into the left branch and the collateral vessels along the epatoduodenal ligament disappeared. In patients with esophageal variceal hemorrhage and portal thrombosis if endoscopy fails, emergency esophageal transection or nonselective portocaval shunting are indicated. The rare patients with only partial portal thrombosis can be treated directly with stenting through an angioradiologic approach. PMID:18644135
Xiao, Zhibo; Yue, Zhendong; Zhao, Hongwei; Fan, Zhenhua; Zhao, Mengfei; He, Fuliang; Dai, Shan; Qiu, Bin; Yao, Jiannan; Lin, Qiushi; Dong, Xiaoqun; Liu, Fuquan
We conducted a single-center randomized trial to compare the efficacy of 8 mm Fluency covered stent and bare stent in transjugular intrahepatic portosystemic shunt (TIPS) for cirrhotic portal hypertension. From January 2006 to December 2010, the covered (experimental group) or bare stent (control group) was used in 131 and 127 patients, respectively. The recurrence rates of gastrointestinal bleeding (18.3% vs. 33.9%, P = 0.004) and refractory hydrothorax/ascites (6.9% vs. 16.5%, P = 0.019) in the experimental group were significantly lower than those in the control group. The cumulative restenosis rates in 1, 2, 3, 4, and 5-years in the experimental group (6.9%, 11.5%, 19.1%, 26.0%, and 35.9%, respectively) were significantly lower (P < 0.001) than those in the control group (27.6%, 37.0%, 49.6%, 59.8%, 74.8%, respectively). Importantly, the 4 and 5-year survival rates in the experimental group (83.2% and 76.3%, respectively) were significantly higher (P = 0.001 and 0.02) than those in the control group (71.7% and 62.2%, respectively). The rate of secondary interventional therapy in the experimental group was significantly lower than that in the control group (20.6% vs. 49.6%; P < 0.001). Therefore, Fluency covered stent has advantages over the bare stent in terms of reducing the restenosis, recurrence, and secondary interventional therapy, whereas improving the long-term survival for post-TIPS patients. PMID:26876503
Domagk, Dirk; Patch, David; Dick, Robert; Grosso, Maurizio; Rousseau, Herve; Otal, Philippe; Goffette, Pierre; Heinecke, Achim; Drees, Markus; Domschke, Wolfram; Menzel, Josef
Purpose: In a prospective multicenter study, efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) were evaluated in the treatment of the complications of portal hypertension using a new self-expanding mesh-wire stent(Memotherm). Methods: One hundred and eighty-one patients suffering from variceal bleeding (either acute or recurrent)or refractory ascites were enrolled. Post interventional follow-up lasted for 8.4 months on average. Differences were analyzed by the log-rank test (chi-square) or Wilcoxon test. Results:Shunt insertion was completed successfully in all patients(n = 181 patients, 100%). During follow-up, shunt occlusion was evident in 23 patients, and shunt stenosis was found in 33 patients (12.7% and 18.2%, respectively). Variceal rebleeding occurred in 20 of 139 patients (14.4%), with at least one episode of bleeding before TIPS treatment. The overall mortality rate of the patients treated by TIPS was 39.8%. In 51.4% of these cases (37 of 72 patients), however, the patients died within 30 days after TIPS replacement. Analysis of subgroups showed that patients who underwent emergency TIPS for acute variceal bleeding had a significantly higher early mortality compared with other patient groups (p= 0.0014). Conclusion: In the present prospective multicenter study, we were able to show that insertion of Memothermstents is an effective tool for TIPS. The occlusion rates seem to be comparable to those reported for the Palmaz stent. It could be shown that in particular, those patients who were treated for acute bleeding were at high risk of early mortality. Consequently, in such a critical condition, the indication for TIPS has to be set carefully.
Sinagra, E; Perricone, G; D'Amico, M; Tinè, F; D'Amico, G
Propranolol is recommended for prophylaxis of variceal bleeding in cirrhosis. Carvedilol is a nonselective beta-blocker with a mild anti-alfa-1-adrenergic activity. Several studies have compared carvedilol and propranolol, yielding inconsistent results. To perform a systematic review and meta-analysis of the randomised clinical trials comparing carvedilol with propranolol for hepatic vein pressure gradient reduction. Studies were searched on the MEDLINE, EMBASE and Cochrane library databases up to November 2013. The weighted mean difference in percent hepatic vein pressure gradient reduction and the relative risk of failure to achieve a hemodynamic response (reduction ≥20% of baseline or to ≤12 mmHg) with each drug were used as measures of treatment efficacy. Five studies (175 patients) were included. Indication to treatment was primary prophylaxis of variceal bleeding in 76% of patients. There were overall three acute (60-90 min after drug administration) and three long-term (after 7-90 days of therapy) comparisons. The summary mean weighted difference in % of reduction in hepatic vein pressure gradient was: acute -7.70 (CI -12.40, -3.00), long-term -6.81 (CI -11.35, -2.26), overall -7.24 (CI -10.50, -3.97), favouring carvedilol. The summary relative risk of failure to achieve a hemodynamic response with carvedilol was 0.66 (CI 0.44, 1.00). Adverse events were nonsignificantly more frequent and serious with carvedilol. However, quality of trials was mostly unsatisfactory. Carvedilol reduces portal hypertension significantly more than propranolol. However, available data do not allow a satisfactory comparison of adverse events. These results suggest a potential for a cautious clinical use. © 2014 John Wiley & Sons Ltd.
Wei, Jishu; Wu, Junli; Gao, Wentao; Li, Qiang; Jiang, Kuirong
Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed. Complete dearterialization of the liver induced acute liver injury, as evidenced by the histological changes, significantly increased serum biochemical markers, decreased ATP content, increased expression of hypoxia- and inflammation-associated genes and proteins, and decreased expression of bile transporter genes. These detrimental changes were extenuated but not fully reversed by partial portal vein arterialization, which also attenuated ductular reaction and fibrosis in completely dearterialized rat livers. Collectively, complete hepatic deprivation causes severe liver injury, including bile infarcts and biloma formation. Partial portal vein arterialization seems to protect against acute ischemia-hypoxia-induced liver injury. PMID:27872855
Kamei, T.; Callery, M.P.; Flye, M.W. )
Pretransplant portal venous (pv) administration of donor antigen induces allospecific partial tolerance. Although the involved mechanism has not been defined, antigen presentation by Kupffer cells (KC) in the liver is considered to be critical. We evaluated the effect of KC blockade on this pv tolerance induction in Buffalo (RT1b) rats receiving Lewis (RT1(1)) cardiac heterotopic allografts. Control rats received no treatment, while experimental animals received 25 X 10(6) ultraviolet B-irradiated (12,000 J/m2) donor spleen cells via either the iv (systemic intravenous) or the pv routes 7 days before transplantation. Gadolinium chloride (GdCl3), a rare earth metal known to inhibit KC phagocytosis, was given (7 mg/kg) 1 and 2 days before pv preimmunization. Cardiac graft prolongation was obtained by pv (MST = 13.3 +/- 1.9 days, n = 6, vs control = 7.3 +/- 0.5 days, n = 6; P less than 0.001) but not by iv preimmunization (7.7 +/- 0.7 days, n = 6, NS vs control). KC blockade abolished the pv tolerance, as indicated by abrogation of graft prolongation (PV + GdCl3 = 8.0 +/- 0.8 days, n = 6, NS vs control). These findings suggest that effective alloantigen uptake by KC in the liver is essential for the induction of pv tolerance in rat cardiac transplantation.
Kawaguchi, Daisuke; Hiroshima, Yukihiko; Kikuchi, Yutaro; Matsuo, Kenichi; Tanaka, Kuniya
Associating liver partition with portal vein occlusion for staged hepatectomy (ALPPS) is a recently developed strategy for inducing rapid hypertrophy of the future liver remnant (FLR). To explore possible mechanisms, we designed the first model of ALPPS with venous congestion (ALPPS+C) in rats. Rats were assigned randomly to 3 experimental groups: ALPPS, ALPPS+C and sham. Hepatic regeneration rate, Ki-67 and histopathology were assessed at 24 h, 48 h, and 7 days postoperatively. Hepatic regeneration rate was much higher for ALPPS+C than for ALPPS at 48 h and 7 days postoperatively (p<0.01). Microscopically, the regenerating liver showed greater hepatocyte density and smaller hepatocyte size in ALPPS+C than in ALPPS (p<0.01 for each). Greater hepatic regeneration in ALPPS+C than in ALPPS confirmed that we established a rat model of ALPPS with benefit from venous congestion. Producing a congested area may contribute importantly to rapid FLR hypertrophy during ALPPS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.
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
Monti, Martina; Ciccone, Valerio; Pacini, Aurora; Roggeri, Riccardo; Monzani, Enrico; Casella, Luigi; Morbidelli, Lucia
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.
Moghadamrad, Sheida; McCoy, Kathy D; Geuking, Markus B; Sägesser, Hans; Kirundi, Jorum; Macpherson, Andrew J; De Gottardi, Andrea
Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH. © 2015 by the American Association for the Study of Liver Diseases.
Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S.; Ferreira, Luciana Garros; Monteiro, Ariadne Santana e Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa
Background The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. Objective This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. Methods The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. Results The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. Conclusion The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects;The chemiluminescence plasmatic NO analysis showed no significant difference between groups andThe Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. PMID:28678928
Zárate Mondragón, F; Romero Trujillo, J O; Cervantes Bustamante, R; Mora Tiscareño, M A; Montijo Barrios, E; Cadena León, J F; Cázares Méndez, M; Toro Monjaraz, E M; Ramírez Mayans, J
Prehepatic portal hypertension in children can be asymptomatic for many years. Once diagnosed, the therapeutic measures (pharmacologic, endoscopic, and surgical) are conditioned by the specific characteristics of each patient. In Mexico, there are no recorded data on the incidence of the disease and patient characteristics. To determine the main clinical, radiologic, and endoscopic characteristics upon diagnosis of these patients at the Instituto Nacional de Pediatría within the time frame of January 2001 and December 2011. A cross-sectional, retrolective, descriptive, and observational study was conducted in which all the medical records of the patients with portal hypertension diagnosis were reviewed. There was a greater prevalence of prehepatic etiology (32/52) (61.5%) in the portal hypertension cases reviewed. Males (62.5%) predominated and 11 of the 32 patients were under 4 years of age. The primary reason for medical consultation was upper digestive tract bleeding with anemia (71.9%) and the main pathology was cavernomatous degeneration of the portal vein (65.6%). Splenoportography was carried out on 17 of the 32 patients. A total of 65.5% of the patients received the combination therapy of propranolol and a proton pump inhibitor. Initial endoscopy revealed esophageal varices in 96.9% of the patients, 12 of whom presented with gastroesophageal varices. Congestive gastropathy was found in 75% of the patients. The varices were ligated in 8 cases, sclerotherapy for esophageal varices was carried out in 5 cases (15.6%), and sclerotherapy for gastric varices was performed in 2 patients. Seventeen patients (53.1%) underwent portosystemic diversion: 10 of the procedures employed a mesocaval shunt and 7 a splenorenal shunt. Nine patients (28.1%) underwent total splenectomy. The primary cause of the disease was cavernomatous degeneration of the portal vein; it was predominant in males and the first symptom was variceal bleeding. Copyright © 2014 Asociación Mexicana
Das, S.; Bhargava, H.N.
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.
Zheng, Xin; Dou, Changwei; Yao, Yingmin; Liu, Qingguang
The aim of this meta-analysis was to determine whether laparoscopic splenectomy (LS) and LS with esophagogastric devascularization (LSED) were the minimally invasive alternative for portal hypertension. A meta-analysis of comparative clinical trials was performed to assess our questions noted above. The databases PubMed, ScienceDirect, and Springerlink were searched. In total, 725 patients with liver cirrhosis and/or portal hypertension from eight published comparative trials were included. The operation time in the laparoscopic group was more than that in the open group [weighted mean difference (WMD) 35.24 (16.74, 53.74); P<.001]. However, there were less intraoperative blood loss [WMD -194.84 (-321.34, -68.34); P=.003] and a shorter postoperative hospital stay [WMD -4.33 (-5.30, -3.36); P<.001] in the laparoscopic group. The incidence of complications was similar in the two groups. In the subgroup studies about LS versus open splenectomy, no significant differences were found in operation time, intraoperative blood loss, and complication rates. The postoperative hospital stay in the LS group was apparently decreased [WMD -4.07 (-4.93, -3.21); P<.001]. Although the operation time of LSED was longer [WMD 43.23 (17.13, 69.32); P=.001], LSED was associated with less intraoperative blood loss [WMD -189.26 (-295.71, -82.81); P<.001] and a shorter postoperative hospital stay [WMD -5.41 (-7.84, -2.98); P<.001]. Meta-analysis did not favor either LSED or open splenectomy with esophagogastric devascularization in term of complication rates. The results of this meta-analysis were in favor of LS and LSED for being a safe, minimally invasion alternative for patients with liver cirrhosis and portal hypertension.
Yu, Bei; Kodavanti, Urmila P; Takeuchi, Minoru; Witschi, Hanspeter; Pinkerton, Kent E
Common laboratory rats and mice fail to develop persistent, progressive pulmonary inflammation found in chronic obstructive pulmonary disease as a result of tobacco smoke exposure. We hypothesized that spontaneously hypertensive rats would be more susceptible than normal Wistar Kyoto rats to acute tobacco smoke-induced pulmonary inflammation due to impaired apoptosis. Spontaneously hypertensive rats display systemic oxidative stress, inflammation, hypercoagulation, and immunosupression, similar to humans with chronic obstructive pulmonary disease. Male spontaneously hypertensive rats and Wistar Kyoto rats were exposed whole-body to tobacco smoke (total particulate concentration 75-85 mg/m(3)) or filtered air for 6 h/day for 2 or 15 days (3 days/wk). Tobacco smoke caused an increase in bronchoalveolar lavage fluid neutrophils at both time points in each strain. Significantly more neutrophils were noted in spontaneously hypertensive rats at 15 days compared to Wistar Kyoto rats. There was a trend of increase for macrophages in spontaneously hypertensive rats at both time points (significant at 2 days). TUNEL assay detected apoptotic cells in bronchoalveolar lavage fluid and lung tissue sections. The number of apoptotic neutrophils in airway walls and bronchoalveolar lavage fluid increased at 2 days in both strains, but at 15 days the effect was much lower in spontaneously hypertensive rats than in Wistar Kyoto rats. Tobacco smoke induces a greater inflammatory response associated with lower apoptotic neutrophils in the lungs of spontaneously hypertensive rats compared to Wistar Kyoto rats. The spontaneously hypertensive rat may be a more relevant animal model of acute tobacco smoke-induced airway inflammation than other laboratory rats.
Hoffman, Matthew J.; Flister, Michael J.; Nunez, Lizbeth; Xiao, Bing; Greene, Andrew S.; Jacob, Howard J.; Moreno, Carol
A 3.7 Mb region of rat chromosome 13 (45.2–49.0 Mb) affects blood pressure (BP) in females only, indicating the presence of gender-specific BP loci in close proximity to the Renin locus. In the present study, we used a series of Dahl salt-sensitive/Mcwi (SS)-13 Brown Norway (BN) congenic rat strains to further resolve BP loci within this region. We identified 3 BP loci affecting female rats only, of which the 2 smaller loci (line9BP3 and line9BP4) were functionally characterized by sequence and expression analysis. Compared with SS, the presence of a 591 Kb region of BN chromosome 13 (line9BP3) significantly lowered BP by 21 mmHg on an 8% NaCl diet (153±7 vs 174±5 mmHg, P<0.001). Unexpectedly, the addition of 23 Kb of BN chromosome 13 (line9BP4) completely erased the female-specific BP protection on 8% NaCl diet, suggesting that BN hypertensive allele(s) reside in this region. The congenic interval of the protective line 9F strain contains 3 genes (Optc, Prelp, and Fmod) and the hypertensive line 9E contains 1 additional gene (Btg2). Sequence analysis of the 2 BP loci revealed a total of 282 intergenic variants, with no coding variants. Analysis of gene expression by RT-qPCR revealed strain- and gender-specific differences in Prelp, Fmod, and Btg2 expression, implicating these as novel candidate genes for female-specific hypertension. PMID:23817491
Lee, Tzu-Cheng; Burghardt, Andrew J.; Yao, Wei; Lane, Nancy E.; Majumdar, Sharmila; Gullberg, Grant T.; Seo, Youngho
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
Sládek, Martin; Sumová, Alena
The functional state of the circadian system of spontaneously hypertensive rats (SHR) differs in several characteristics from the functional state of normotensive Wistar rats. Some of these changes might be due to the compromised ability of the central pacemaker to entrain the peripheral clocks. Daily body temperature cycles represent one of the important cues responsible for the integrity of the circadian system, because these cycles are driven by the central pacemaker and are able to entrain the peripheral clocks. This study tested the hypothesis that the aberrant peripheral clock entrainment of SHR results from a compromised peripheral clock sensitivity to the daily temperature cycle resetting. Using cultured Wistar rat and SHR fibroblasts transfected with the circadian luminescence reporter Bmal1-dLuc, we demonstrated that two consecutive square-wave temperature cycles with amplitudes of 2.5°C are necessary and sufficient to restart the dampened oscillations and entrain the circadian clocks in both Wistar rat and SHR fibroblasts. We also generated a phase response curve to temperature cycles for fibroblasts of both rat strains. Although some of the data suggested a slight resistance of SHR fibroblasts to temperature entrainment, we concluded that the overall effect it too weak to be responsible for the differences between the SHR and Wistar in vivo circadian phenotype. PMID:24116198
Oluyemi, Aderemi; Amole, Adeniyi
Multiple duodenal ulcers are an uncommon finding in portal hypertensive duodenopathy (PHD). They represent a potential source of clinically significant bleeding from the upper gastrointestinal system in patients with cirrhosis. As this particular ulcer entity in relation to PHD has no distinguishing symptoms aside from those relating to the consequent bleeding, most of them are found either on routine endoscopic screening for cirrhotics or on endoscopic examination for cause(s) of bleeding in this patient population. The case documented below highlights many of the aspects of pathogenesis, associations, and consequences of this unique endoscopic finding in cirrhotic patients. PMID:23118766
Oluyemi, Aderemi; Amole, Adeniyi
Multiple duodenal ulcers are an uncommon finding in portal hypertensive duodenopathy (PHD). They represent a potential source of clinically significant bleeding from the upper gastrointestinal system in patients with cirrhosis. As this particular ulcer entity in relation to PHD has no distinguishing symptoms aside from those relating to the consequent bleeding, most of them are found either on routine endoscopic screening for cirrhotics or on endoscopic examination for cause(s) of bleeding in this patient population. The case documented below highlights many of the aspects of pathogenesis, associations, and consequences of this unique endoscopic finding in cirrhotic patients.
Ishii, Masakazu; Hattori, Akira; Numaguchi, Yasushi; Ma, Xiuyang; Nagasaka, Tetsuro; Tsujimoto, Masafumi; Murohara, Toyoaki; Kobayashi, Hiroshi; Mizutani, Sigehiko
We have tested the effects of aminopeptidase A (APA), MgSO(4) and various conventional antihypertensive drugs on hypertension in pregnant spontaneously hypertensive rats (SHRs) and examined the effects on both fetal heart and kidney. We used recombinant human APA, which has been recently shown to work as an antihypertensive agent in SHRs (n=5). Each drug was administered from gestational day 10 to day 20 and each dose was increased daily up to 10 fold until the end of treatment except for MgSO(4) (n=5 per each group). Blood pressure (BP) was monitored and fetal kidneys and heart were histologically examined. The antihypertensive effects of the drugs were in the following order: hydralazine>aminopeptidase A and angiotensin receptor blockers (ARBs), candesartan>MgSO(4) and methyldopa. Microscopic examination showed that fetal exposure to candesartan is associated with poor proximal tubular differentiation in the kidney and that to MgSO(4) is associated with poor blood vessel formation in the heart, respectively. Our present study showed that APA is one of the candidates for antihypertensive agents in hypertension during pregnancy.
Hayman, G Thomas; Laulederkind, Stanley J F; Smith, Jennifer R; Wang, Shur-Jen; Petri, Victoria; Nigam, Rajni; Tutaj, Marek; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary
The Rat Genome Database (RGD;http://rgd.mcw.edu/) provides critical datasets and software tools to a diverse community of rat and non-rat researchers worldwide. To meet the needs of the many users whose research is disease oriented, RGD has created a series of Disease Portals and has prioritized its curation efforts on the datasets important to understanding the mechanisms of various diseases. Gene-disease relationships for three species, rat, human and mouse, are annotated to capture biomarkers, genetic associations, molecular mechanisms and therapeutic targets. To generate gene-disease annotations more effectively and in greater detail, RGD initially adopted the MEDIC disease vocabulary from the Comparative Toxicogenomics Database and adapted it for use by expanding this framework with the addition of over 1000 terms to create the RGD Disease Ontology (RDO). The RDO provides the foundation for, at present, 10 comprehensive disease area-related dataset and analysis platforms at RGD, the Disease Portals. Two major disease areas are the focus of data acquisition and curation efforts each year, leading to the release of the related Disease Portals. Collaborative efforts to realize a more robust disease ontology are underway. Database URL:http://rgd.mcw.edu.
Hayman, G. Thomas; Laulederkind, Stanley J. F.; Smith, Jennifer R.; Wang, Shur-Jen; Petri, Victoria; Nigam, Rajni; Tutaj, Marek; De Pons, Jeff; Dwinell, Melinda R.; Shimoyama, Mary
The Rat Genome Database (RGD; http://rgd.mcw.edu/) provides critical datasets and software tools to a diverse community of rat and non-rat researchers worldwide. To meet the needs of the many users whose research is disease oriented, RGD has created a series of Disease Portals and has prioritized its curation efforts on the datasets important to understanding the mechanisms of various diseases. Gene-disease relationships for three species, rat, human and mouse, are annotated to capture biomarkers, genetic associations, molecular mechanisms and therapeutic targets. To generate gene–disease annotations more effectively and in greater detail, RGD initially adopted the MEDIC disease vocabulary from the Comparative Toxicogenomics Database and adapted it for use by expanding this framework with the addition of over 1000 terms to create the RGD Disease Ontology (RDO). The RDO provides the foundation for, at present, 10 comprehensive disease area-related dataset and analysis platforms at RGD, the Disease Portals. Two major disease areas are the focus of data acquisition and curation efforts each year, leading to the release of the related Disease Portals. Collaborative efforts to realize a more robust disease ontology are underway. Database URL: http://rgd.mcw.edu PMID:27009807
Singh, Amrita; Khan, Samsroz Ahmad; Choudhary, Rajesh
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
Price-Haywood, Eboni G.; Luo, Qingyang
Background: We describe the role of primary care reengineering in the Ochsner Health System (OHS) patient portal implementation strategy and compare subsequent trends in service utilization and disease control among portal users vs nonusers within this context. Methods: This retrospective cohort study includes 101,019 patients with hypertension or diabetes who saw an OHS primary care provider (PCP) between 2012 and 2014. Inverse probability treatment weighting was used to reduce case-mix differences between study groups. We used generalized estimating equation modeling to compare changes in encounter rates (PCP, telephone, specialty services, emergency department [ED], inpatient hospitalization), blood pressure (BP), and hemoglobin A1c (HbA1c). Results: Age, sex, race, comorbidities, insurance, preindex utilization, and portal use were associated with changes in utilization, BP, and HbA1C; however, the strength and direction of these differences varied. An adjusted analysis comparing portal users to nonusers showed an increase in PCP (rate ratio per patient per year of 1.18, 95% confidence interval [CI] 1.14-1.22) and telephone encounter rates (1.15, 95% CI 1.08-1.22; both P<0.001) but no significant differences in specialty, ED, or inpatient hospitalization encounters. Among patients with preindex systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, portal users compared to nonusers had a greater decline in their BP, although the between-group difference was small (mmHg [SE], –1.1 [0.42] and –1.2 [0.34], respectively; both P<0.01). Portal users with diabetes compared to nonusers with diabetes also had greater decreases in HbA1c (all patients, % [SE], –0.13 [0.06]; patients with a preindex HbA1c ≥8, –0.43 [0.13], both P<0.05). Conclusion: Our findings may reflect patient factors and system-level portal implementation strategies that focused heavily on accessibility to care. PMID:28331456
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
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
Gallego, B; Arévalo, M A; Flores, O; López-Novoa, J M; Pérez-Barriocanal, F
To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction + diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction + diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction + diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 microg/30 min, respectively) and much higher in the DH kidney (770 +/- 106 microg/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression
Ahn, Mi Young; Jung, Yi Sook; Jee, Sang Deok; Kim, Chan Shik; Lee, Su Hwan; Moon, Chang Hyun; Cho, Sung Ig; Lee, Byung Mu; Ryu, Kang Sun
The present study examined the effect of the methanol extract of Isaria sinclairii, a kind of Donchunghacho (Tochukaso), on blood pressure in spontaneously hypertensive rats (SHR). Blood pressure and heart rate were measured after treatment with the methanol extract of I. sinclairii by the indirect tail-cuff method and the direct in vivo model. Starting at 12 weeks of age, male SHR were treated with the extracts for 2 or 4 weeks. We found that, when compared to untreated control SHR, oral treatment with I. sinclairii methanol extract (30 mg/kg/day) remarkably decreased systolic blood pressure from 200 to 112 mmHg and decreased diastolic blood pressure from 114 to 88 mmHg. Furthermore, efficacy of methanol extract of I. sinclairii was superior to captopril (30 mg/kg/mL, positive control), an angiotensin-converting enzyme inhibitor, with a lowering effect that dropped systolic blood pressure from 201 to 130 mmHg and diastolic blood pressure from 102 to 92 mmHg. However, in normal Wistar Kyoto rats, I. sinclairii methanol extract did not significantly change the normal blood pressure, suggesting that this type of Dongchunghacho has a selective effect against hypertension. Therefore, methanol extract of I. sinclairii may be used as an anti-hypertensive food/agent. Furthermore, this extract also has multiple actions such as No production in endothelial cells, inhibiting thrombin-induced blood coagulation by thrombin and mildly decreasing in prostaglandin E2 levels in cultured macrophage cells, all of which might contribute to protection against atherogenesis and thrombus formation. HPLC and MS analysis of methanol extract of I. sinclairii revealed the presence of adenosine.
Su-Hong, Chen; Qi, Chen; Bo, Li; Jian-Li, Gao; Jie, Su; Gui-Yuan, Lv
Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels. PMID:25784949
Loch, David; Levick, Scott; Hoey, Andrew; Brown, Lindsay
The pleiotropic effects of statins represent potential mechanisms for the treatment of end-organ damage in hypertension. This study has investigated the effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1% NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, inflammation with perivascular and interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of ventricular action potential duration at 28 days. Rosuvastatin-treated rats received 20 mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation, but did not modify hypertension or vascular dysfunction. We conclude that the pleiotropic effects of rosuvastatin include attenuation of aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in rats without altering systolic blood pressure.
Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria
In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney. The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure
Edwards, G.; Zygmunt, P. M.; Högestätt, E. D.; Weston, A. H.
1. The effects of the cytochrome P450 inhibitors, proadifen, clotrimazole and 17-octadecynoic acid (17-ODYA) on K-currents in freshly-isolated single cells derived from rat portal vein and on mechanical activity in whole veins were studied. 2. When cells were stepped from -90 mV to a series of test potentials (from -80 to +50 mV), a delayed rectifier current (IK(V)) and an A-type current (IK(A)) could be identified. Proadifen (10 microM), clotrimazole (30 microM) and 17-ODYA (5 microM) each inhibited IK(V) but had little effect on IK(A). 3. When cells were held at -10 mV to inactivate the time-dependent K-currents, IK(V) and IK(A), levcromakalim (3 microM) induced a time-independent outward K-current (IK(ATP)) which was totally inhibited by clotrimazole (30 microM) and almost fully inhibited by proadifen (10 microM). 17-ODYA (5 microM) had no effect on IK(ATP) and exerted only a minor inhibitory action on this current at 20 microM. 4. 17-ODYA (5 microM) potentiated current flow through the large conductance, Ca-sensitive K-channel (BKCa). In contrast, proadifen (10 microM) had no effect on IBK(Ca) whereas clotrimazole (30 microM) exerted a small but significant inhibitory action. 5. Proadifen (10 microM) and clotrimazole (30 microM) each inhibited the magnitude but increased the frequency of spontaneous contractions in whole portal veins. 17-ODYA (5 microM) had no effect on spontaneous contractions but these were inhibited when the concentration of 17-ODYA was increased to 50 microM. 6. The spasmolytic effect of levcromakalim on spontaneous contractions was antagonized by proadifen (10-30 microM) in a concentration-dependent manner but 17-ODYA (up to 50 microM) was without effect. 7. These results in portal vein show that cytochrome P450 inhibitors exert profound effects on a variety of K-channel subtypes. This suggests that enzymes dependent on this cofactor may be important regulators of K-channel activity in smooth muscle. The relevance of these findings for the
Loirand, G; Mironneau, C; Mironneau, J; Pacaud, P
1. Using the whole-cell recording mode of the patch-clamp technique, we investigated the calcium currents in isolated cells from rat portal vein in short-term primary culture. 2. From a holding potential of -70 mV the cells presented two types of calcium currents with 5 mM-extracellular calcium: one type was activated by small depolarizations and inactivated quickly (fast calcium current), whereas the other required stronger depolarizations for activation and inactivated more slowly (slow calcium current). 3. Isradipine (PN 200-110) blocked the slow calcium current at concentrations 300 times lower than those used to block the fast inward current. The isradipine-induced inhibition was voltage-dependent for the slow calcium current and voltage-independent for the fast calcium current. 4. The slow calcium current was lost during internal perfusion with a 0.5 microM-Ca2+ containing solution, and during stimulation of the cell at high frequencies (0.1-0.2 Hz) within 5-10 min. The fast calcium current was unchanged under these experimental conditions. 5. Steady-state inactivation curves for both fast and slow calcium currents showed differences in their voltage dependence. Half-maximal and complete inactivations of the fast calcium current were obtained at -50 and -30 mV while those of the slow calcium current were obtained at -20 and +10 mV. 6. Studied with the two-pulse protocol, inactivation of the slow calcium current was dependent on both membrane potential and calcium influx while that of the fast calcium current appeared only dependent on membrane potential. 7. Two types of calcium currents, differing in potential dependence of inactivation, and in sensitivities to dihydropyridines, stimulation frequency and intracellular calcium concentration were identified in cultured smooth muscle cells isolated from portal vein. PMID:2557429
Abramoff, Tamara; Guil, María J; Morales, Vanina P; Hope, Sandra I; Soria, Celeste; Bianciotti, Liliana G; Vatta, Marcelo S
The ablation of olfactory bulb induces critical changes in dopamine, and monoamine oxidase activity in the brain stem. Growing evidence supports the participation of this telencephalic region in the regulation blood pressure and cardiovascular activity but little is known about its contribution to hypertension. We have previously reported that in the olfactory bulb of normotensive rats endothelins enhance noradrenergic activity by increasing tyrosine hydroxylase activity and norepinephrine release. In the present study we sought to establish the status of noradrenergic activity in the olfactory bulb of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Different steps in norepinephrine transmission including tyrosine hydroxylase activity, neuronal norepinephrine release and uptake were assessed in the left and right olfactory bulb of DOCA-salt hypertensive rats. Increased tyrosine hydroxylase activity, and decreased neuronal norepinephrine uptake were observed in the olfactory bulb of DOCA-salt hypertensive rats. Furthermore the expression of tyrosine hydroxylase and its phosphorylated forms were also augmented. Intriguingly, asymmetrical responses between the right and left olfactory bulb of normotensive and hypertensive rats were observed. Neuronal norepinephrine release was increased in the right but not in the left olfactory bulb of DOCA-salt hypertensive rats, whereas non asymmetrical differences were observed in normotensive animals. Present findings indicate that the olfactory bulb of hypertensive rats show an asymmetrical increase in norepinephrine activity. The observed changes in noradrenergic transmission may likely contribute to the onset and/or progression of hypertension in this animal model.
Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B
The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI < 2.06 mg/g - RWT > 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT < 0.71; and concentric LVH, LVMI > 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.
Bolterman, Rodney J; Manriquez, Melissa C; Ortiz Ruiz, M Clara; Juncos, Luis A; Romero, J Carlos
There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.
Sharpe, Amanda L; Andrade, Mary Ann; Herrera-Rosales, Myrna; Britton, Steven L; Koch, Lauren G; Toney, Glenn M
Exposure to chronic intermittent hypoxia (CIH) is an animal model that mimics the repetitive bouts of hypoxemia experienced by humans with sleep apnea. Rats exposed to CIH develop hypertension that depends on the activation of sympathetic nerve activity (SNA). Since obesity and metabolic syndrome have been linked to neurogenic hypertension and sleep apnea, and because sleep apnea can adversely affect aerobic exercise capacity, we tested the hypothesis that rats bred for selection of low aerobic capacity running (LCR) would have a greater hypertensive response to CIH than rats bred for high aerobic capacity running (HCR). Blockade of ganglionic transmission was performed to compare the contribution of SNA to the maintenance of resting mean arterial pressure (MAP). Next, hypertensive responses to 7 days of CIH were compared across LCR and HCR rats (14-16 mo old). Finally, the contribution of the hypothalamic paraventricular nucleus (PVN) to the maintenance of SNA and hypertension after CIH was determined and compared across groups. Although LCR rats were less active and had greater body weights than HCR rats, resting MAP, the contribution of ongoing SNA to the maintenance of MAP, and hypertensive responses to CIH were similar between groups. Contrary to our hypothesis, chemical inhibition of the PVN with muscimol (1 mmol/100 nl) caused a larger fall of MAP in HCR rats than in LCR rats. We conclude that LCR rats do not have resting hypertension or an exaggerated hypertensive response to CIH. Interestingly, the maintenance of CIH hypertension in LCR rats compared with HCR rats appears less reliant on ongoing PVN neuronal activity.
Tomimura, Suely; Silva, Bianca Passos Assumpção; Sanches, Iris Callado; Canal, Marina; Consolim-Colombo, Fernanda; Conti, Felipe Fernandes; Angelis, Katia De; Chavantes, Maria Cristina
Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats. PMID:25211315
Dorofeieva, N O; Kuz'menko, M O; Shimans'ka, T V; Sagach, V F
We studied cardiohemodynamics and efficiency Frank-Starling mechanism in 6-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats, using pressure-volume (PV) conductance catheter system (Millar Instruments, Houston, TX) to evaluate systolic and diastolic function in vivo. Rats were anesthetized with urethane. Cardiohemodynamics analyzed using PVAN 3.6 (Millar Instruments). We found that systolic and diastolic function of the heart in spontaneously hypertensive rats were lower, than in controls. We have shown, inhibition of the efficiency Frank-Starling mechanism, increasing arterial stiffness in spontaneously hypertensive rats. It's shown, less efficiency heart work, with more energy and more oxygen consumption in spontaneously hypertensive rats, may be associated with increasing arterial stiffness and decrease functional reserve of the heart.
Yao, Libin; Li, Chonghui; Ge, Xinlan; Wang, Hongdong; Xu, Kesen; Zhang, Aiqun; Dong, Jiahong
Background Portal vein ligation (PVL) combined with in situ splitting (ISS) has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. Materials and Methods Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR), Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. Results The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (p<0.01). The expression of Ki-67 in hepatocytes in the regenerating liver lobe was stronger in the PVL+ISS group than in the PVL group at 48 and 72 h (p<0.01). There was a significant reduction in microcirculation blood perfusion of the left median lobe before and after ISS. Liver biochemical determinations and histopathology demonstrated more severe hepatocyte injury in the PVL+ISS group. Both the mRNA levels of TNF-α and IL-6 and the protein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. Conclusions The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS. PMID:25144490
Yao, Libin; Li, Chonghui; Ge, Xinlan; Wang, Hongdong; Xu, Kesen; Zhang, Aiqun; Dong, Jiahong
Portal vein ligation (PVL) combined with in situ splitting (ISS) has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR), Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (p<0.01). The expression of Ki-67 in hepatocytes in the regenerating liver lobe was stronger in the PVL+ISS group than in the PVL group at 48 and 72 h (p<0.01). There was a significant reduction in microcirculation blood perfusion of the left median lobe before and after ISS. Liver biochemical determinations and histopathology demonstrated more severe hepatocyte injury in the PVL+ISS group. Both the mRNA levels of TNF-α and IL-6 and the protein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.
Mac Cormack, W.P.; Roson, M.I.; Maquieira, M.K.; Mendez, M.A.; Santoro, F.M.; Morera, S.; de la Riva, I.J.
Exchangeable /sup 22/Na (ExNa), total body water (TBW) and the inulin space (InSp) were determined in two-kidney, two-clip (2K-2C) hypertensive and sham operated (normotensive) control rats 6-8 weeks after surgery. TBW (ml/kg lean body weight) was the same in hypertensive and sham rats. In contrast, ExNa (mEq/kglbw) and InSp (ml/kglbw) significantly increased (p less than 0.01) in rats whose hypertension did not exceed 170 mmHg. Consequently, sham, moderate hypertensive (less than 170 mmHg) and severe hypertensive (less than 170 mmHg) animals showed equal TBW but differed in body water distribution in that moderately hypertensive animals displayed a redistribution of water in favor of the extracellular space.
Kovaleva, Iu O; Artem'eva, M M; Medvedev, O S; Medvedeva, N A
We have studied the role of female sex hormone estradiol in the development of hypoxic pulmonary arterial hypertension. Previously, it was shown that the development of pulmonary hypertension in Wistar female rats is accompanied by a twofold increase in the estradiol level. Ovariectomy reduces the degree of pulmonary hypertension in these animals. In this work, the effect of various chronic doses of exogenous estradiol (5 and 15 microg/kg per day) on the development of hypoxic pulmonary hypertension in Wistar female rats has been studied. Pulmonary hypertension was induced by exposure to hypobaric hypoxia (10 h a day for 2 weeks) at simulated altitude of 5000 m (O2 concentration reduced to 10%). The administration of estradiol in different doses (5 and 15 microg/kg per day) for 21 day initiated the development of pulmonary hypertension in ovariectomized Wistar female rats.
Ganten, U; Schröder, G; Witt, M; Zimmermann, F; Ganten, D; Stock, G
The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.
Poddar, Ujjal; Borkar, Vibhor; Yachha, Surender Kumar; Srivastava, Anshu
Background and study aims: In view of the paucity of literature, we carried out this audit to evaluate the safety and efficacy of N- butyl, 2-cynoacrylate glue injection therapy in secondary prophylaxis of gastric varices in children. Patients and methods: Consecutive children (≤ 18 years) with non-cirrhotic portal hypertension who presented with bleeding from gastric varices and who had undergone cyanoacrylate glue injection therapy were included. They were evaluated for safety, efficacy and complications. Their long-term outcomes and follow-up were recorded. Results: Over 11 years, 28 children with median age 13 (range, 8 to 18) years (68 % boys), underwent cyanoacrylate glue injection for bleeding gastric varices. In 25 (89 %) cases, extrahepatic portal venous obstruction was the etiology and isolated gastric varices were the source of the bleeding. Primary and secondary gastric variceal bleeding was seen in 11 (39 %) and 17 (61 %) children, respectively. A total 36 sessions with median volume of 2 (range, 1 – 5) mL of glue injections were required (2 sessions in 8 children). Hemostasis was achieved in all and 57 % had gastric variceal obliteration. Two children had early (< 1 month) rebleeding and 2 children had late rebleeding. One child had gastric ulcer. Over a median follow-up of 24 (8 – 98) months, 14 children underwent surgery (12 porto-systemic shunt), 2 were lost to follow-up, 1 died and there was no recurrence of bleeding in the remaining 11. Conclusions: Cyanoacrylate glue injection is highly effective mode of secondary prophylaxis of bleeding gastric varices in children with non-cirrhotic portal hypertension. Rebleeding occurred in 14 % but treatment-related complications were uncommon. However, a large controlled clinical trial is required to confirm our findings. PMID:27757413
Hayano, Shunsuke; Naganuma, Atsushi; Okano, Yudai; Suzuki, Yuhei; Shiina, Keisuke; Yoshida, Haruka; Hayashi, Eri; Uehara, Sanae; Hoshino, Takashi; Miyamae, Naomi; Kudo, Tomohiro; Ishihara, Hiroshi; Ogawa, Akira; Sato, Ken; Kakizaki, Satoru
A 51-year-old woman was diagnosed with mixed connective tissue disease (MCTD) in 2011. She underwent treatment with prednisolone. Her hepatobiliary enzyme level increased, and multiple nodules were found in both liver lobes in abdominal imaging studies. Ultrasonography revealed large and small hyperechoic lesions with indistinct or well-defined borders. No findings of classic hepatocellular carcinoma or liver cirrhosis were observed on contrast-enhanced computed tomography, but some nodules showed an enhanced effect of the central lesion that was characteristic of focal nodular hyperplasia (FNH) in an arterial phase. On gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging, slightly high-intensity nodules, 10-40mm in size, were observed on T1- and T2-weighted images. The nodules showed highest intensities in the hepatocyte phase and were enhanced with the uptake of Gd-EOB-DTPA as compared with the background liver. FNH was suspected based on the imaging findings, but we performed a liver tumor biopsy for differential diagnosis of the malignant lesion. Based on the immunohistopathological examination results, the final diagnosis was idiopathic portal hypertension associated with nodular regenerative hyperplasia (NRH)-like nodule of the liver. Benign nodular hepatocellular lesions are caused by abnormal hepatic circulation and were previously known as anomalous portal tract syndrome. Our case of atypical NRH with large nodules may be included in this disease entity. Here, we report a rare case of MCTD with NRH-like nodules and idiopathic portal hypertension with a review of literature.
Poddar, Ujjal; Borkar, Vibhor; Yachha, Surender Kumar; Srivastava, Anshu
Background and study aims: In view of the paucity of literature, we carried out this audit to evaluate the safety and efficacy of N- butyl, 2-cynoacrylate glue injection therapy in secondary prophylaxis of gastric varices in children. Patients and methods: Consecutive children (≤ 18 years) with non-cirrhotic portal hypertension who presented with bleeding from gastric varices and who had undergone cyanoacrylate glue injection therapy were included. They were evaluated for safety, efficacy and complications. Their long-term outcomes and follow-up were recorded. Results: Over 11 years, 28 children with median age 13 (range, 8 to 18) years (68 % boys), underwent cyanoacrylate glue injection for bleeding gastric varices. In 25 (89 %) cases, extrahepatic portal venous obstruction was the etiology and isolated gastric varices were the source of the bleeding. Primary and secondary gastric variceal bleeding was seen in 11 (39 %) and 17 (61 %) children, respectively. A total 36 sessions with median volume of 2 (range, 1 - 5) mL of glue injections were required (2 sessions in 8 children). Hemostasis was achieved in all and 57 % had gastric variceal obliteration. Two children had early (< 1 month) rebleeding and 2 children had late rebleeding. One child had gastric ulcer. Over a median follow-up of 24 (8 - 98) months, 14 children underwent surgery (12 porto-systemic shunt), 2 were lost to follow-up, 1 died and there was no recurrence of bleeding in the remaining 11. Conclusions: Cyanoacrylate glue injection is highly effective mode of secondary prophylaxis of bleeding gastric varices in children with non-cirrhotic portal hypertension. Rebleeding occurred in 14 % but treatment-related complications were uncommon. However, a large controlled clinical trial is required to confirm our findings.
Chen, Hui; Yin, Jun; Deng, Yanpin; Yang, Min; Xu, Lingling; Teng, Fukang; Li, Defang; Cheng, Yufan; Liu, Sha; Wang, Dong; Zhang, Tingting; Wu, Wanying; Liu, Xuan; Guan, Shuhong; Jiang, Baohong; Guo, Dean
Although a number of medicines are available for the management of hypertension, the organ damage induced by hypertension is not resolved. The aim of this study was to investigate the protection of ginsenoside Rg1 (Rg1) against vascular remodeling and organ damage in spontaneously hypertensive rats (SHR). Male SHR were treated with 5, 10 or 20 mg/kg Rg1 through intraperitoneal injection per day for 1 month. SHR or Wistar-Kyoto rats (WKY) receiving vehicle (saline) was used as control. Blood pressure detection and pathological stain, transmission electron microscope, immunohistochemical assay were used to elucidate the protection of Rg1. Blood pressures were not different between control SHR rats and Rg1 treated SHR rats, but Rg1 improved the aortic outward remodeling by lowering the lumen diameter and reducing the media thickness according the histopathological and ultrastructural detections. Rg1 also protected the retinal vessels against inward remodeling detected by immunohistochemical assay. Furthermore, Rg1 attenuated the target heart and kidney damage with improvement on cardiac and glomerular structure. These results suggested that Rg1 held beneficial effects on vascular structure and further protected against the organ-damage induced by hypertension. These findings also paved a novel and promising approach to the treatment of hypertensive complications.
Yan, Zhiqiang; Hu, Ya'e; Liu, Bo; Jiang, Zonglai
This study inquired about the role of tumor suppressor PTEN in the arterial remodeling of Ang II induced hypertension. The expression of PTEN of aorta was examined in the aortic-constricted hypertensive rats (hypertension group), in the aortic-constricted hypertensive rats treated with captopril(hypertension and captopril group), and in the rats having undergone sham operation (control group). At day 28 after surgery, the aortas were collected from the groups. The expression of PTEN mRNA was detected by RT-PCR. The expression and location of PTEN protein were determined by immunohistochemistry. The results showed that the expression of PTEN in aorta of the hypertension group was significantly lower than that of the hypertension and captopril group, and similarly lower than that of the control group. The intensity of PTEN-positive immunohistochemical production in aorta of the hypertension group was weaker than that of the hypertension and captopril group, and likewise, it was weaker than the control. PTEN-positive immunohistochemical production was located in VSMC of aorta. The findings indicated that the expression of PTEN is reduced in hypertensive aorta, that the reduced PTEN experession can be reversed by captopril treatment, that AngII and the increased mechanical strain may participate in regulating expression of PTEN, and that PTEN may play a role in the arterial remodeling induced by hypertension.
Muscará, Marcelo N; Lovren, Fina; McKnight, Webb; Dicay, Michael; Soldato, Piero del; Triggle, Christopher R; Wallace, John L
Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension and to interfere with the effectiveness of some anti-hypertensive therapies. In this study, we tested the effects of a gastric-sparing, nitric oxide-releasing derivative of aspirin (NCX-4016) on hypertension in rats. Hypertension was induced by administering L-NAME in the drinking water (400 mg l−1). Groups of rats were treated daily with aspirin, NCX-4016 or vehicle. NCX-4016 significantly reduced blood pressure relative to the aspirin-treated group over the 2-week period of treatment. Aspirin and, to a lesser extent, NCX-4016 suppressed whole blood thromboxane synthesis. In anaesthetized rats, acute intravenous administration of NCX-4016 caused a significant fall in mean arterial pressure in hypertensive rats, but was devoid of such effects in normotensive controls. In vitro, NCX-4016 relaxed phenylephrine-pre-contracted aortic rings obtained from both normotensive and hypertensive rats, and significantly reduced their responsiveness to the contractile effects of phenylephrine. These results suggest that NCX-4016 reduces blood pressure in hypertensive rats, not simply through the direct vasodilatory actions of the nitric oxide released by this compound, but also through possible interference with the effects of endogenous pressor agents. These properties, added to its anti-thrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients. PMID:11498517
Shcherbin, Iu I; Tsyrlin, V A
In anaesthetized normotensive (Wistar) and hypertensive (SHR) rats, sympathetic and somatic reflexes were studied before and after cervical spinal cord transection. Single shock stimulation of a peripheral afferent nerve of brachial plexus produced reflex discharges in the cervical sympathetic trunk and the radial nerve. In rats with intact brain stem, evoked response in the cervical sympathetic trunk was composed of three components, but evoked response in radial nerve consisted of two components. The total somato-sympathetic reflex in hypertensive rats was more on 54 % than the somato-sympathetic reflex in normotensive rats. The total somato-somatic reflex in hypertensive rats was more on 70 % than the somato-somatic reflex in normotensive rats. In rats with transected brain stem, evoked response in the cervical sympathetic trunk was composed of two components, but evoked response in radial nerve consisted of one component. After neuraxis transection the total sympathetic and somatic reflexes in normotensive rats decreased by 85 and 83 %, respectively. The total sympathetic and somatic reflexes in hypertensive rats decreased by 88 and 84 %, respectively. However, the peak value of evoked discharges in sympathetic and somatic nerves were more in hypertensive rats than in normotensive rats. Suprasegmental and spinal mechanisms responsible for the augmentation of both sympathetic and somatic reflexes are discussed.
Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu
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
Zhang-James, Yanli; Middleton, Frank A; Faraone, Stephen V
The spontaneously hypertensive rat (SHR) has been widely used as a model for studies of hypertension and attention deficit/hyperactivity disorder. The inbred Wistar-Kyoto (WKY) rat, derived from the same ancestral outbred Wistar rat as the SHR, are normotensive and have been used as the closest genetic control for the SHR, although the WKY has also been used as a model for depression. Notably, however, substantial behavioral and genetic differences among the WKY substrains, usually from the different vendors and breeders, have been observed. These differences have often been overlooked in prior studies, leading to inconsistent and even contradictory findings. The complicated breeding history of the SHR and WKY rats and the lack of a comprehensive understanding of the genetic background of different commercial substrains make the selection of control rats a daunting task, even for researchers who are mindful of their genetic heterogeneity. In this study, we examined the genetic relationship of 16 commonly used WKY and SHR rat substrains using genome-wide SNP genotyping data. Our results confirmed a large genetic divergence and complex relationships among the SHR and WKY substrains. This understanding, although incomplete without the genome sequence, provides useful guidance in selecting substrains and helps to interpret previous reports when the source of the animals was known. Moreover, we found two closely related, yet distinct WKY substrains that may provide novel opportunities in modeling psychiatric disorders.