Home About us Contact
|
Home About us Contact | ||
|
|
||
Portal Pressure (portal + pressure)
Selected AbstractsDialysis Reduces Portal Pressure in Patients With Chronic Hepatitis CARTIFICIAL ORGANS, Issue 7 2010Sandeep Khurana Abstract The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient ,6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high-grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late-stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient ,6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient ,6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 ± 3.3 and 7.98 ± 0.4 vs. 25.9 ± 2.0 and 1.66 ± 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late-stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty-three of the 92 patients with early fibrosis had a hepatic venous pressure gradient ,6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long-term hemodialysis may reduce portal pressure in these patients. [source] Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangementHEPATOLOGY, Issue 1 2003Agustín Albillos Intestinal bacterial overgrowth and translocation, both common in cirrhosis with ascites, may lead to the activation of monocytes and lymphocytes, increased levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide present in cirrhosis. Bacterial endotoxin promotes the synthesis of lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that binds to CD14. This study was designed to evaluate LBP levels and their correlation to the immune response and the hemodynamic status in cirrhotic patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin, nitrites, and systemic vascular resistance were determined before and 4 weeks after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was elevated in 42% of ascitic cirrhotic patients (15.7 ± 0.7 versus 6.06 ± 0.5 ,g/mL, P < .01). In 60% of high LBP patients, endotoxin was within normal range. Among ascitic patients, those with high LBP showed greater (P < .05) levels of sCD14, tumor necrosis factor , (TNF-,), interleukin 6 (IL-6), nitrites + nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the cirrhotic patients with high LBP, norfloxacin normalized (P < .01) LBP (from 16.6 ± 0.5 to 5.82 ± 0.8 , g/mL) and sCD14; reduced the level of cytokines, NOx/creatinine, and renin; and increased vascular resistance; but lacked effect in patients with normal LBP. Portal pressure was unchanged after norfloxacin in another group of 18 cirrhotic patients with high and 19 with normal LBP. In conclusion, the subset of ascitic cirrhotic patients with marked immune and hemodynamic derangement is identified by increased LBP levels. Amelioration of these abnormalities by norfloxacin suggests the involvement of enteric bacteria or their products in the triggering of the process. [source] Effects of endothelin-1 on portal-systemic collaterals of common bile duct-ligated cirrhotic ratsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004C.-C. Chan Abstract Background/Aims, Endothelin-1 (ET-1) may induce intrahepatic vasoconstriction and consequently increase portal pressure. Endothelin-1 has been shown to exert a direct vasoconstrictive effect on the collateral vessels in partially portal vein-ligated rats with a high degree of portal-systemic shunting. This study investigated the collateral vascular responses to ET-1, the receptors in mediation and the regulation of ET-1 action by nitric oxide and prostaglandin in cirrhotic rats with a relatively low degree of portal-systemic shunting. Methods, The portal-systemic collaterals of common bile duct-ligated (BDL) cirrhotic rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10,10,10,7 m) with or without BQ-123 (ETA receptor antagonist, 2 × 10,6 m), BQ-788 (ETB receptor antagonist, 10,7 m) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of N, -nitro-L-arginine (NNA, 10,4 M), indomethacin (INDO, 10,5 M) or in combination were assessed. Results, Endothelin-1 significantly increased the perfusion pressures of portal-systemic collaterals. The ET-1-induced constrictive effects were inhibited by BQ-123 or BQ-123 plus BQ-788 but not by BQ-788 alone. The inhibitory effect was greater in the combination group. Pretreatment of NNA or NNA plus INDO equivalently enhanced the response of ET-1 while pretreatment of INDO alone exerted no effect. Conclusion, Endothelin-1 has a direct vasoconstrictive effect on the collaterals of BDL cirrhotic rats, mainly mediated by ETA receptor. Endogenous nitric oxide may play an important role in modulating the effects of ET-1 in the portal-systemic collaterals of BDL cirrhotic rats. [source] Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats,HEPATOLOGY, Issue 4 2007Mercedes Fernandez Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein,ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, ,-smooth muscle actin and PDGFR-, expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Conclusions: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension. (HEPATOLOGY 2007.) [source] Atorvastatin and portal pressure,HEPATOLOGY, Issue 4 2007Daniel Zamora-Valdés M.D. No abstract is available for this article. [source] Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: A double-blind RCTHEPATOLOGY, Issue 6 2003Juan Carlos García-Pagán M.D. Nonselective ,-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding. [source] Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosisHEPATOLOGY, Issue 2 2003Lia Bellis Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo (n = 12) and a standard liquid meal 15 minutes later. Hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and hepatic blood flow (HBF) were measured at baseline and 15, 30, and 45 minutes after a meal. ISMN significantly attenuated the postprandial increase in portal pressure as compared with placebo (peak HVPG increase: 2.4 ± 1.4 mm Hg vs. 5.2 ± 2.1 mm Hg, P = .002). Percentual increases in HBF were similar in both groups. MAP decreased slightly in ISMN group (,7.5% ± .5%; P < .01 vs. baseline). These effects were also observed in patients on chronic propranolol therapy. In conclusion, hepatic NO supplementation by low doses of ISMN effectively reduces the postprandial increase of portal pressure in cirrhosis, with only a mild effect on arterial pressure. The same was observed in patients receiving propranolol. Our results suggest that therapeutic strategies based on selective hepatic NO delivery may improve the treatment of portal hypertension. [source] Fractal dimension can distinguish models and pharmacologic changes in liver fibrosis in ratsHEPATOLOGY, Issue 4 2002Frédéric Moal Fractal analysis measures the complexity of geometric structures. The aim of this study was to evaluate the feasibility and accuracy of fractal analysis in liver fibrosis. A total of 77 rats were included: 10 sham, 46 with fibrosis secondary to bile duct ligation (BDL), and 21 with fibrosis due to CCl4 intoxication. Measurements included the fractal dimension of Kolmogorov (Dk), histologic lesions, the area of fibrosis by image analysis, liver hydroxyproline content, messenger RNA fibronectin, serum hyaluronate level, and portal pressure. Fibrotic rats were given placebo, octreotide, or O2 -vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO). Intraobserver agreement of Dk was excellent with the intraclass (ic) correlation coefficient ric = 0.91 (P < .0001) as well as the interobserver agreement with ric = 0.88 (P < .001). Dk was correlated with other measurements or markers of fibrosis: the area of fibrosis (r = 0.75; P < .0001), hydroxyproline content (r = 0.51; P < .001), serum hyaluronate level (r = 0.52; P < .001), and portal pressure (r = 0.52; P < .01). Dk was significantly different between the 2 models of fibrosis (P < .0001), unlike the area of fibrosis, and this relationship was independent of other histologic lesions. The significant decrease in fibrosis observed with octreotide or V-PYRRO/NO was similarly reflected by Dk or the area of fibrosis. The diagnostic accuracy for the fibrosis model was 97% with the 5 main measurements or markers of fibrosis studied, with Dk isolated at the first step by stepwise analysis. In conclusion, fractal analysis is suitable for analyzing liver fibrosis and has excellent reproducibility. This is the only quantitative morphometric method that can discriminate among the models of fibrosis and is sensitive enough to detect pharmacologically induced changes in liver fibrosis. [source] Increasing intra-abdominal pressure increases pressure, volume, and wall tension in esophageal varicesHEPATOLOGY, Issue 4 2002Angels Escorsell Many daily activities cause acute elevations of intra-abdominal pressure (IAP). In portal hypertensive cirrhotic patients, increased IAP increases absolute portal pressure and azygos blood flow, suggesting that it may have detrimental consequences at the esophageal varices. The aim of this study was to investigate the effects of increased IAP on variceal pressure, size, and wall tension. Endosonography and a noninvasive endoscopic pressure gauge were used to measure variceal pressure, radius, wall tension, and volume in baseline conditions and after increasing IAP by 10 mm Hg using an inflatable girdle in 14 patients with cirrhosis and esophageal varices. Increasing IAP markedly increased variceal pressure (from 13.3 ± 4.2 to 17.4 ± 4.6 mm Hg; P = .0001) and radius (from 2.9 ± 1.0 to 3.9 ± 1.1 mm; P = .0001). Consequently, wall tension dramatically increased (from 38.7 ± 13.6 to 65.9 ± 23.8 mm Hg · mm, +78%; P = .0001). Variceal volume increased significantly from 1,264 ± 759 to 2,025 ± 1,129 mm3 (P = .0001). In conclusion, in portal hypertensive cirrhotic patients, increases in IAP have deleterious effects on variceal hemodynamics, markedly increasing the volume, pressure, and wall tension of the varices. Increases in IAP may contribute to the progressive dilatation that precedes the rupture of the varices in portal hypertension. [source] Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascitesHEPATOLOGY, Issue 1 2000María Pérez-Paramo Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with ,-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of 99mTc-diethylenetriaminepentaacetic acid [99mTc-DTPA]), and transit (geometric center ratio of 51Cr) were assessed in 29 rats with carbon tetrachloride (CCl4 ) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a 99mTc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a 99mTc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation. [source] Effect of porto-systemic shunting on NOS expression after extended hepatectomy in ratsHEPATOLOGY RESEARCH, Issue 1 2009Hironori Hayashi Aim:, Several surgical procedures have been developed for reducing portal vein pressure to prevent postoperative liver injury. Nitric oxide synthase expression (NOS) induced by elevation of portal vein pressure is thought to play an important role in liver regeneration, but the details are not well understood. Methods:, Rats in the control group and in the subcutaneous splenic transposition (SST) group underwent 90% partial hepatectomy. Survival and portal vein pressure were analyzed. The serum IL-6 and TNF-, levels were measured by enzyme-linked immunosorbent assay (ELISA). Hepatocyte proliferation and apoptosis 12 hours after hepatectomy were analyzed immunohistochemically. The protein and messenger RNA expression of inducible and endothelial NOS were analyzed using Western blotting and quantitative reverse transcriptase polymerase chain reaction, respectively. Results:, The survival rate of the SST group was significantly higher. Portal vein pressure, TNF-, level and the apoptotic index were significantly lower in the SST group. Twelve hours after surgery, liver inducible NOS (iNOS) protein expression was significantly lower in the SST group. However, protein expression of endothelial NOS was not significantly different between the groups. Conclusion:, Inducible NOS expression after extended hepatectomy is related to the effects of porto-systemic shunting on the splanchnic circulation. Also, iNOS induction and concomitant nitric oxide generation appear to participate in the cytotoxicity of excessive portal pressure after extended hepatectomy. [source] Recent role of splenectomy in chronic hepatic disordersHEPATOLOGY RESEARCH, Issue 12 2008Toru Ikegami For years splenectomy in hepatic disorders has been indicated only for the treatment of gastro-esophageal varices. However, with recent advances in medical and surgical treatments for chronic hepatic disorders, the use of splenectomy has been greatly expanded, such that splenectomy is used for reversing hypersplenism, for applying interferon treatment for hepatitis C, for treating hyperdynamic portal circulation associated with intractable ascites, and for controlling portal pressure during small grafts in living donor liver transplantation. Such experiences have shown the importance of portal hemodynamics, even in cirrhotic livers. Recent advances in surgical techniques have enabled surgeons to perform splenectomy more safely and less invasively, but the procedure still has considerable clinical outcomes. Splenectomy in hepatic disorders may become a more common procedure with expanded indications. However, it should also be noted that the long-term effects of splenectomy, in terms of improved hematological or hepatic function, is still not guaranteed. Moreover, the impact of splenectomy on immunologic status remains unclear and needs to be elucidated in both experimental and clinical settings. [source] Simvastatin effects on portal-systemic collaterals of portal hypertensive ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2010Hui-Chun Huang Abstract Background and Aim:, Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. Methods:, Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from ,2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM,0.1 µM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A2 synthase (TXA2 -S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA2 -S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1, and TXB2 levels were performed in parallel groups without AVP. Results:, Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1, concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA2 -S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness. Conclusion:, Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities. [source] Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approachJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2009Lílian Amorim Curvêlo Abstract Background and Aim:, Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. Methods:, Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. Results:, The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child,Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). Conclusions:, The present data show no correlation between the presence or the severity of PHG and portal pressure, Child,Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors. [source] Role of endothelin in endotoxin-induced hepatic microvascular dysfunction in rats fed chronically with ethanolJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2001Yoshinori Horie Abstract Background: We examined the role of endothelin in endotoxin-induced hepatic microcirculatory disturbance in pair-fed rats given a liquid diet containing ethanol or isocaloric control. Methods and Results: One lobe of the liver was observed with the use of an intravital microscope. Erythrocytes (RBCs) labeled with fluorescein isothiocyanate (FITC) were injected, and the flow velocity of the FITC-RBCs in the sinusoids was measured with an off-line velocimeter. The flow velocity decreased 30 min after 1 mg/kg of lipopolysaccharide (LPS) was administered to the controls, and portal pressure (PP) was increased at 60 min. In ethanol-fed rats, however, both the flow velocity and PP increased in the early phase (at 10 min), and in the late phase, flow velocity decreased and PP increased more than in the controls. The LPS-induced decrease in flow velocity was blunted, when BQ-123, an antagonist of endothelin receptor subtype A, was infused into ethanol-fed rats, and BQ-123 also attenuated the change in PP. The plasma endothelin levels in both systemic and portal blood of the ethanol-fed rats were higher than in the controls. Conclusions: These results suggest that endothelin plays a role in the LPS-induced hepatic microcirculatory disturbance, especially in alcohol-fed animals. [source] Tezosentan normalizes hepatomesenteric perfusion in a porcine model of cardiac tamponadeACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009A. ÅNEMAN Background: To investigate endothelin-1 (ET-1)-dependent hepatic and mesenteric vasoconstriction, and oxygen and lactate fluxes in an acute, fixed low cardiac output (CO) state. Methods: Sixteen anesthetized, mechanically ventilated pigs were studied. Cardiac tamponade was established to reduce portal venous blood flow (QPV) to 2/3 of the baseline value. CO, hepatic artery blood flow (QHA), QPV, hepatic laser-Doppler flow (LDF), hepatic venous and portal pressure, and hepatic and mesenteric oxygen and lactate fluxes were measured. Hepatic arterial (RHA), portal (RHP) and mesenteric (Rmes) vascular resistances were calculated. The combined ETA,ETB receptor antagonist tezosentan (RO 61-0612) or normal saline vehicle was infused in the low CO state. Measurements were made at baseline, after 30, 60, 90 min of tamponade, and 30, 60, 90 min following the infusion of tesozentan at 1 mg/kg/h. Results: Tamponade decreased CO, QPV, QHA, LDF, hepatic and mesenteric oxygen delivery, while hepatic and mesenteric oxygen extraction and lactate release increased. RHA, RHP and Rmes all increased. Ninety minutes after tesozentan, QPV, LDF and hepatic and mesenteric oxygen delivery and extraction increased approaching baseline values, but no effect was seen on CO or QHA. Hepatic and mesenteric handling of lactate converted to extraction. RHA, RHP and Rmes returned to baseline values. No changes were observed in these variables among control animals not receiving tesozentan. Conclusion: In a porcine model of acute splanchnic hypoperfusion, unselective ET-1 blockade restored hepatomesenteric perfusion and reversed lactate metabolism. These observations might be relevant when considering liver protection in low CO states. [source] ,-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysisLIVER INTERNATIONAL, Issue 8 2009Marco Senzolo Abstract Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and ,-blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of ,-blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non-RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using ,-blockers were evaluated. We performed a meta-analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Results: Three RCT and three retrospective studies in which ,-blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non-responders. Conclusions: This analysis suggests a role of ,-blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding. [source] Effects of probiotic therapy on portal pressure in patients with cirrhosis: a pilot studyLIVER INTERNATIONAL, Issue 7 2009Puneeta Tandon Abstract Background: Recent literature has supported the role of bacterial translocation as a mediator of splanchnic vasodilatation and portal hypertension. The objective of this study was to determine whether the probiotic VSL#3 would reduce portal pressure in patients with cirrhosis. Methods: Eight patients with compensated or very early decompensated cirrhosis and hepatic venous pressure gradient (HVPG) >10 mmHg, received 2 months of VSL#3 (3600 billion bacteria daily). The HVPG, intestinal permeability, endotoxin, tumour necrosis factor (TNF)-,, interleukin (IL)-6, IL-8, renin and aldosterone were measured at baseline and study end. Results: There was no change in the HVPG or intestinal permeability from baseline to study end but there was a trend to reduction in plasma endotoxin (P=0.09), a mild but significant increase in serum TNF-, (P=0.02) and a significant reduction in plasma aldosterone (P=0.03). Conclusions: Within the limitations of small sample size, there does not appear to be a benefit of probiotic therapy for portal pressure reduction in patients with compensated or early decompensated cirrhosis. The reductions in endotoxin and aldosterone suggest possible beneficial effects of probiotics for this patient population. The clinical significance of the small but unexpected increase in TNF-, is unclear. Future studies are planned in patients with decompensated cirrhosis. [source] Model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor and its correlation with portal pressure in patients with liver cirrhosisLIVER INTERNATIONAL, Issue 4 2007Teh-Ia Huo Abstract Background: The models for end-stage liver disease (MELD) and serum sodium (SNa) are important prognostic markers in cirrhosis. A novel index, MELD to SNa ratio (MESO), was developed to amplify the opposing effect of MELD and SNa on outcome prediction. Methods: A total of 213 cirrhotic patients undergoing hepatic venous pressure gradient (HVPG) measurement were retrospectively analyzed. Results: The MESO index correlated with HVPG (r=0.258, P<0.001) and Child,Pugh score (,=0.749, P<0.001). Using mortality as the end point, the area under receiver operating characteristic curve (AUC) was 0.860 for SNa, 0.795 for the MESO index and 0.789 for MELD (P values all >0.3) at 3 months. Among patients with Child,Pugh class A or B, the MESO index had a significantly higher AUC compared with MELD (0.80 vs. 0.766, P<0.001). A MESO index <1.6 identified 97% of patients who survived at 3 months and the predicted survival rate was 96.5%. In survival analysis, MESO index >1.6 independently predicted a higher mortality rate (relative risk: 3.32, P<0001) using the Cox model. Conclusions: The MESO index, which takes into account the predictive power of both MELD and SNa, is a useful prognostic predictor for both short- and long-term survival in cirrhotic patients. [source] The cytoprotective effects of addition of activated protein C into preservation solution on small-for-size grafts in ratsLIVER TRANSPLANTATION, Issue 1 2010Naohisa Kuriyama Small-for-size liver grafts are a serious obstacle for partial orthotopic liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, is known to have cell-protective properties due to its anti-inflammatory and antiapoptotic activities. This study was designed to examine the cytoprotective effects of a preservation solution containing APC on small-for-size liver grafts, with special attention paid to ischemia-reperfusion injury and shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1) increased 7-day graft survival; (2) decreased initial portal pressure and improved hepatic microcirculation; (3) decreased levels of aminotransferase and improved histological features of hepatic ischemia-reperfusion injury; (4) suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced hepatic expression of tumor necrosis factor , and interleukin 6; (6) decreased serum levels of hyaluronic acid, which indicated attenuation of sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide via up-regulated hepatic endothelial nitric oxide synthesis expression together with down-regulated hepatic inducible nitric oxide synthase expression; (8) decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular apoptosis by down-regulated caspase-8 and caspase-3 activities. These results suggest that a preservation solution containing APC is a potential novel and safe product for small-for-size liver transplantation, alleviating graft injury via anti-inflammatory and antiapoptotic effects and vasorelaxing conditions. Liver Transpl 16:1,11, 2010. © 2009 AASLD. [source] Flow in Lymphatic Networks: Interaction between Hepatic and Intestinal Lymph VesselsMICROCIRCULATION, Issue 4 2001RANDOLPH H. STEWART ABSTRACT Objective: Lymph from both the liver and intestine flows into the cisterna chyli. We hypothesized that increasing liver lymph flow would increase cisterna chyli pressure and, thereby, decrease intestinal lymph flow, potentiating intestinal edema formation. Methods: Anesthetized dogs were instrumented to measure and manipulate portal vein pressure and cisterna chyli pressure. The effects of directly increasing portal pressure with and without directly increasing cisterna chyli pressure on intestinal wet-to-dry ratio and intestinal ascites formation rate were determined. Target values for portal and cisterna chyli pressures were determined following elevation of inferior vena caval pressure to levels seen in patients with obstructive caval disease. Results: Direct elevation of portal pressure (Pport) alone to 17.5 mm Hg caused a significant increase in intestinal wet-to-dry ratio (3.98 ± 0.24 vs. 3.40 ± 0.43) and the rate of ascites formation (0.36 ± 0.12 vs. 0.05 ± 0.03 mL/g dry wt/h). Simultaneous direct elevation of cisterna chyli pressure to 6.0 mm Hg and Pport to 17.5 mm Hg caused further increases in intestinal wet-to-dry ratio (5.52 ± 1.20) and ascites formation (0.57 ± 0.11 mL/g dry wt./h). Conclusions: Inferior vena caval hypertension increases liver lymph flow that elevates cisterna chyli pressure, which inhibits intestinal lymph flow and augments intestinal edema formation. [source] Deceleration of Regenerative Response Improves the Outcome of Rat with Massive HepatectomyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010M. Ninomiya Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS-398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS-398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS-398 treatment. In the 90% PH model, administration of NS-398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver. [source] Dialysis Reduces Portal Pressure in Patients With Chronic Hepatitis CARTIFICIAL ORGANS, Issue 7 2010Sandeep Khurana Abstract The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient ,6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high-grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late-stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient ,6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient ,6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 ± 3.3 and 7.98 ± 0.4 vs. 25.9 ± 2.0 and 1.66 ± 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late-stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty-three of the 92 patients with early fibrosis had a hepatic venous pressure gradient ,6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long-term hemodialysis may reduce portal pressure in these patients. [source] Hepatic venous outflow reconstruction in adult living donor liver transplants without portal hypertensionCLINICAL TRANSPLANTATION, Issue 2 2004Diego Bogetti Abstract:, Graft congestion is one of the causes of poor graft function in segmental liver transplantation. Three factors are implicated in segmental graft congestion: graft size, hepatic venous outflow and portal inflow. The graft size must be matched to the body weight, which is conventionally done by using graft to body weight ratio. Hepatic blood outflow must be optimized by hepatic vein reconstruction, which can be complicated. High portal blood flow has been shown to be detrimental to small-for-size grafts. These factors are strictly connected to each other. They can all contribute to graft congestion and poor function, while one factor can compensate for the others and decrease congestion. Ideally, all the accessory veins should be reconstructed, if possible, to maximize the outflow. In the absence of portal hypertension and with an adequate sized graft, complex venous reconstruction may not be necessary. We present a case report of an adult living donor liver transplant with the favorable conditions of normal portal pressure and a large sized graft, but complicated by the presence of several accessory hepatic veins. A simple hepatic vein anastomosis was sufficient for adequate outflow and prompt graft function. [source] Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis,HEPATOLOGY, Issue 1 2007Rajeshwar P. Mookerjee Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases. Our study assessed whether ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in alcoholic hepatitis patients, and determined any relationship with severity of portal hypertension (hepatic venous pressure gradient measurement) and outcome. Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher (P = 0.001) than cirrhosis alone, and correlated with ADMA measurement. Plasma ADMA and SDMA were significantly higher in alcoholic hepatitis patients and in nonsurvivors. Dimethylarginine-dimethylamino-hydrolase protein expression was reduced and protein-arginine-methyltransferase-1 increased in alcoholic hepatitis livers. ADMA, SDMA and their combined sum, which we termed a dimethylarginine score, were better predictors of outcome compared with Pugh score, MELD and Maddrey's discriminant-function. Conclusion: Alcoholic hepatitis patients have higher portal pressures associated with increased ADMA, which may result from both decreased breakdown (decreased hepatic dimethylarginine-dimethylamino-hydrolase) and/or increased production. Elevated dimethylarginines may serve as important biological markers of deleterious outcome in alcoholic hepatitis. (HEPATOLOGY 2007;45:62,71.) [source] | ||||||||||||||||||||||