Increase In Portal Pressure Research Articles

LPS exacerbates endothelin-1 induced activation of cytosolic phospholipase A 2 and thromboxane A 2 production from Kupffer cells of the prefibrotic rat liver

Thromboxane A2 (TXA2) has been suggested to play a significant role in the development of portal hypertension in fibrosis, and Kupffer cell (KC) derived TXA2 has been shown to mediate the hyperresponsiveness of the portal circulation to the vasoconstrictive actions of endothelin-1 (ET-1) during endotoxemia. The aim of this study was to determine whether the double stresses of prefibrotic changes and endotoxemia additively activate KC to increase release of TXA2 in response to ET-1, resulting in elevated portal resistance. One week Bile duct ligation (BDL) rats and sham-operated controls were subjected to isolated liver perfusions following LPS or saline for 6h. In a separate experiment, KC were isolated from BDL or sham rats and incubated with LPS or saline for 6h before the ET-1 treatment. The double stresses of early fibrosis and LPS resulted in a greater sustained increase in portal pressure in response to ET-1 in BDL rats, and this increase correlated well with the much enhanced release of TXA2 in the perfusate. Media from the cultured KC showed significantly greater TXA2 release in response to ET-1 in BDL group than those in sham group, and LPS exacerbated this effect. Protein levels of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2, and thromboxane synthase were also significantly elevated in KC from BDL rats. ET-1 produced a marked increase in cPLA2 activation as measured by the phosphorylation of cPLA2 in KC of both BDL and sham groups. LPS greatly exacerbated the activation of cPLA2. The data suggest that the double stresses additively activate KC with an upregulation of the key enzymes in the TXA2 biosynthesis and release increased amount of TXA2 via the augmented activation of cPLA2 in response to ET-1, which leads to the increased portal resistance and ultimately hepatic microcirculatory dysfunction.

Hepatic pre‐sinusoidal vessels contract in anaphylactic hypotension in rabbits

The purpose of this study was to determine whether anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction, and the effects of anaphylaxis on hepatic segmental vascular resistances and liver weight in isolated perfused rabbit livers. The rabbits were sensitized by subcutaneous injection of antigen of 2.5 mg ovalbumin with complete Freund's adjuvant three times at 1 week interval. One week after sensitization, anaphylaxis was induced by an injection of 2.5 mg ovalbumin into the jugular vein of pentobarbital anaesthetized rabbits or the perfusate of rabbit livers perfused via the portal vein at a constant flow. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- (R(pre)) and post-sinusoidal (R(post)) resistances were calculated for the isolated perfused livers. An antigen injection into the sensitized rabbits caused not only a decrease in systemic arterial pressure from 79 +/- 2 to 40 +/- 4 mmHg, but also an increase in portal venous pressure (P(pv)) from 9.5 +/- 2.2 to 24.1 +/- 3.9 cmH(2)O. Portal hypertension persisted for 8 min after the antigen injection. An injection of antigen into the perfusate caused a marked increase in P(pv) from 5.4 +/- 0.1 to 28.6 +/- 2.4 cmH(2)O at 6 min, but only a slight increase in double occlusion pressure from 2.2 +/- 0.2 to 3.8 +/- 0.2 cmH(2)O, resulting in a selective increase in R(pret) rather than R(post). Concomitant with the hepatic pre-sinusoidal constriction, liver weight loss occurred. Anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction which is characterized by pre-sinusoidal contraction.

Norfloxacin vs Ceftriaxone in the Prophylaxis of Infections in Patients With Advanced Cirrhosis and Hemorrhage

Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding. One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion. Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups. Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.

Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state

Increased nitric oxide (NO) is the main factor leading to the hyperdynamic circulation associated with advanced portal hypertension (PHT), but the initial mechanisms and the magnitude of increase in portal pressure required to trigger NO production are not known. We addressed these issues by studying systemic and splanchnic hemodynamics and endothelial NO synthase (eNOS) and VEGF expression in rats with different degrees of portal hypertension. Portal vein ligation (PVL) performed over needles of three different calibers (16-, 18-, and 20-gauge) yielded different degrees of PHT and portosystemic shunting. Compared with sham rats, all three groups of PVL rats exhibited features of hyperdynamic circulation. Rats with minimal portal hypertension (PVL with a 16-gauge needle) showed an early increase in VEGF and eNOS expression selectively at the jejunum. Immunofluorescence showed that VEGF expression was located in highly vascularized areas of the mucosa. Inhibition of VEGF signaling markedly attenuated the increase in eNOS expression. In conclusion, mild increases in portal pressure are enough to upregulate eNOS at the intestinal microcirculation, and this occurs, at least in part, through VEGF upregulation.

The action of extracellular NAD+ on gluconeogenesis in the perfused rat liver

In the rat liver NAD+ infusion produces increases in portal perfusion pressure and glycogenolysis and transient inhibition of oxygen consumption. The aim of the present work was to investigate the possible action of this agent on gluconeogenesis using lactate as a gluconeogenic precursor. Hemoglobin-free rat liver perfusion in antegrade and retrograde modes was used with enzymatic determination of glucose production and polarographic assay of oxygen uptake. NAD+ infusion into the portal vein (antegrade perfusion) produced a concentration-dependent (25-100 microM) transient inhibition of oxygen uptake and gluconeogenesis. For both parameters inhibition was followed by stimulation. NAD+ infusion into the hepatic vein (retrograde perfusion) produced only transient stimulations. During Ca2+-free perfusion the action of NAD+ was restricted to small transient stimulations. Inhibitors of eicosanoid synthesis with different specificities (indo-methacin, nordihydroguaiaretic acid, bromophenacyl bromide) either inhibited or changed the action of NAD+. The action of NAD+ on gluconeogenesis is probably mediated by eicosanoids synthesized in non-parenchymal cells. As in the fed state, in the fasted condition extracellular NAD+ is also able to exert two opposite effects, inhibition and stimulation. Since inhibition did not manifest significantly in retrograde perfusion it is likely that the generating signal is located in pre-sinusoidal regions.

Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension

Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow-dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO). Ascorbic acid reverts endothelial dysfunction in other vascular disorders, via the increase of NO bioavailability through the neutralization of superoxide anions, thus preventing the scavenging of NO by superoxide. This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis. Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics, ascorbic acid, and malondialdehyde (MDA). Patients were randomly allocated to receive ascorbic acid (3 g, intravenously, n = 15) or placebo (n = 12) followed by a liquid meal. A third group received ascorbic acid followed by a sham meal (n = 10). Measurements were repeated after 30 minutes (hepatic venous pressure gradient at 15 and 30 minutes). Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls. Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient (4% +/- 7% vs. 18% +/- 10% in placebo at 30 minutes, P < .001). Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics. In conclusion, patients with cirrhosis exhibited intrahepatic endothelial dysfunction, associated with decreased levels of ascorbic acid and increased levels of MDA. Ascorbic acid improved intrahepatic endothelial dysfunction, blunting the postprandial increase in portal pressure. These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension.

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Intrahepatic Flow Disturbance: Possibility of a Hidden Cause of Drug Toxicity

The liver has an intricate microvascular system that allows homogenous perfusion throughout the organ. However, the regulatory mechanisms of intrahepatic circulation are still unclear, and the effects of drugs on this system have rarely been reported. Oxethazaine, a topical anesthetic, was incidentally found to induce a consistent increase in portal pressure in the isolated perfused rat liver, which led us to characterize this phenomenon. For this, a vital staining method was developed to detect microcirculatory alterations in the isolated liver. Using this method, not only vasoconstrictors like endothelin-1, but the drugs oxethazaine and clomipramine, a tricyclic antidepressant, were found to induce flow redistribution to the deeper and hilar portions of the liver with minimal perfusion at the periphery, which was due to a short-circuit flow at the center owing to the constriction of the intrahepatic portal vein branches. Hepatic nerve stimulation also produced a similar flow disturbance. Since the portal pressure increases by these compounds were inhibited by the Rho-kinase inhibitors Y27632 and HA1077, portal vein branches may employ a Rho-kinase-dependent pathway for sustained contraction. However, oxethazaine, clomipramine, and endothelin-1 may activate this pathway differently. The intrahepatic flow disturbance could play a hidden role in drug toxicity of certain drugs.

Liver parenchyma heterogeneity in the response to extracellular NAD+

The perfused rat liver responds intensely to NAD+ infusion (20-100 microM). Increases in portal perfusion pressure and glycogenolysis and transient inhibition of oxygen consumption are some of the effects that were observed. The aim of the present work was to investigate the distribution of the response to extracellular NAD+ along the hepatic acinus. The bivascularly perfused rat liver was used. Various combinations of perfusion directions (antegrade and retrograde) and infusion routes (portal vein, hepatic vein and hepatic artery) were used in order to supply NAD+ to different regions of the liver parenchyma, also taking advantage of the fact that its extracellular transformation generates steep concentration gradients. Oxygen uptake was stimulated by NAD+ in retrograde perfusion (irrespective of the infusion route) and transiently inhibited in antegrade perfusion. This indicates that the signal causing oxygen uptake inhibition is generated in the periportal area. The signal responsible for oxygen uptake stimulation is homogenously distributed. Stimulation of glucose release was more intense when NAD+ was infused into the portal vein or into the hepatic artery, indicating that stimulation of glycogenolysis predominates in the periportal area. The increases in perfusion pressure were more pronounced when the periportal area was supplied with NAD+ suggesting that the vasoconstrictive elements responding to NAD+ predominate in this region. The response to extracellular NAD+ is thus unequally distributed in the liver. As a paracrine agent, NAD+ is likely to be released locally. It can be concluded that its effects will be different depending on the area where it is released.

Prolonged Q–Tc interval in mild portal hypertensive cirrhosis

The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic venous pressure gradient (HVPG) < 12 mmHg. Forty-four patients with cirrhosis and HVPG < 12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic patients with clinically significant portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. The fraction with prolonged Q-T(c) interval (> 0.440 s(1/2)) was similar in the two cirrhotic groups (49 vs 50%, ns) and significantly above that of the controls (5%, P < 0.005). Q-T(c) was normal in patients with normal HVPG. Likewise, mean Q-T(c) was 0.449 and 0.447 s(1/2) in the two cirrhotic groups (ns), values which are significantly above that of the controls (0.410 s(1/2), P < 0.01). In the mild portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P < 0.02). Delayed repolarisation of the myocardium already occurs in a substantial fraction of patients with cirrhosis with only a mild increase in portal pressure. The prolonged Q-T(c) interval may be related to liver dysfunction and to the presence of portal hypertension.

Hepatic microcirculation after continuous 7-day elevated intra-abdominal pressure in cirrhotic rats

It is well known that IAP elevation, even at the level of 10mmHg used for laparoscopic surgery leads to an increase in portal pressure and decrease in portal blood flow. Since hepatic hemodynamics are already disturbed in cirrhotics, we decided to investigate the possible role of chronically elevated intra-abdominal pressure thus simulating ascites under tension-in liver perfusion and function in cirrhotic portal hypertensive rats. Four groups of 10 rats each were studied, including two control and two CCl(4)(-) induced cirrhotic groups. These were subdivided into normal and increased IAP. Elevation and maintenance of increased IAP to 20mmHg for 7 consecutive days was achieved by means of an intraperitonially placed balloon filled with water. Liver microcirculation was assessed by means of laser-Doppler technique, while venous blood samples were obtained for determination of the biochemical parameters of liver function. Cirrhotic rats showed a significant decrease in liver microcirculation in relation to controls (15.7+/-2.5 versus 23.2+/-2.2, p=0.001). Elevation of IAP led to a significant decrease (p=0.001) of liver microcirculation in both groups, i.e. from 15.7+/-2.5 to 12.7+/-1.7 units of flow in cirrhotics and from 23.2+/-2.2 to 15.9+/-2.6 units of flow in control rats. Alkaline phosphatase, alanine aminotransferase and bilirubin concentrations were found increased in cirrhotics in comparison to controls (p=0.05). IAP elevation resulted in a further impairment of liver function, but the differences, were not statistically significant. In conclusion, chronically elevated IAP in cirrhotic rats is associated with a significant impairment of the already decreased hepatic blood flow due to liver cirrhosis. Thus, the possible consequences of decreased liver perfusion must be taken under consideration in any case of severe cirrhosis presented with ascites under tension.

Hepatic venoconstriction is involved in anaphylactic hypotension in rats

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

63 Mild increases in portal pressure upregulate VEGF and ENOS in the intestinal microcirculatory bed leading to vasodilatation and the hyperdynamic circulation

63 Mild increases in portal pressure upregulate VEGF and ENOS in the intestinal microcirculatory bed leading to vasodilatation and the hyperdynamic circulation

Portal Vein Arterialization in a Patient with Acute Liver Failure

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die waiting for a transplant because of donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment (1). Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of the hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy and in toxic-induced ALF model (2–4). Furthermore, we have reported a case of PVA performed to rescue a dearterialized liver graft with 80% hepatocyte necrosis as a bridge for retransplantation (5). We present here a clinical case of ALF successfully treated with a modified PVA technique. A 25-year-old female was admitted to our hospital for abdominal pain and asthenia. Blood tests revealed severe coagulopathy and hypertransaminasemia (Table 1). Her medical history was unremarkable except for a recent administration of tetracyclines for acne. The viral or autoimmune hepatitis markers were absent. Her liver function deteriorated rapidly and the neurological status worsened to deep coma requiring respiratory assistance within 2 days. This dramatic clinical course and the persistent delay of a donor prompted us to attempt, with the informed consent of the family, a PVA procedure by anastomosing the inferior mesenteric artery to the inferior mesenteric vein. At surgery, the liver was macroscopically necrotic and a biopsy showed a severe confluent parenchymal necrosis. In the following days, the neurological conditions improved rapidly as did the hepatic function tests. The coma resolved within 2 days and she was extubated 3 days after arterialization. Ten days later, an angiography demonstrated the shunt patency (Fig. 1 panel A) and only a mild increase in portal pressure (22 mm Hg). The patient liver function tests progressively improved except for a marked cholestasis requiring several carbon hemodialysis sessions and a reduced prothrombin activity. A liver biopsy performed 22 days from PVA revealed residual small foci of lobular necrosis and mild inflammation associated, however, with severe cholestasis and collapse of the reticuline fibres. To avoid long-term complications related to portal hypertension, the arteriovenous shunt was closed with a metal coil during an angiographic procedure (Fig. 1 panel B) leading to a normalization of the portal blood flow. The patient was discharged from hospital 29 days after PVA and liver tests progressively normalized in the following months. At present, she is in good clinical conditions, back at work and liver tests are normal.TABLE 1: Blood test parameters and neurological status before and after portal vein arterializationFIGURE 1. An angiography performed through a percutaneous transfemoral catheter (C) inserted in the inferior mesenteric artery 10 days after portal vein arterialization shows the patency of the surgical shunt between the inferior mesenteric artery and the inferior mesenteric vein (IMV). Note the immediate portal vein (PV) visualization after the injection of contrast through the inferior mesenteric artery. Some collateral vessels (CV) developed from the IMV, which was interrupted below the anastomosis (panel A). The arteriovenous shunt was closed 22 days after PVA by metal coil positioning (arrow) in the inferior mesenteric artery by percutaneous angiographyic procedure. Note that the inferior mesenteric vein (IMV) appears slightly enlarged (panel B).Although we cannot rule out the possibility that this patient could have recovered spontaneously, this event is very rare in deeply comatose patients with non-acetaminophen-induced ALF. By bringing the portal vein oxygen saturation up to an arterial blood level, thus likely matching the increased metabolic demand of the regenerating cells, a temporary PVA procedure can represent a new tool in the multidisciplinary approach to ALF. However, clinical trials are needed to validate this positive initial experience before PVA becomes part of clinical practice. Bruno Nardo Roberto Montalti Lorenza Puviani Gerardo Martinelli Antonino Cavallari Department of Surgery, Intensive Care Unit and Transplantation, S. Orsola Hospital, University of Bologna, Bologna, Italy Paolo Caraceni Department of Internal Medicine, Cardioangiology, Hepatology, S. Orsola Hospital, University of Bologna, Bologna, Italy Cristina Rossi Department of Radiology, S. Orsola Hospital, University of Bologna, Bologna, Italy

207 Ascorbic acid improves intrahepatic endothelial dysfunction and attenuates the postprandial increase in portal pressure in patients with cirrhosis

207 Ascorbic acid improves intrahepatic endothelial dysfunction and attenuates the postprandial increase in portal pressure in patients with cirrhosis

The Third Gas: H2S Regulates Perfusion Pressure in Both the Isolated and Perfused Normal Rat Liver and in Cirrhosis *

The regulation of sinusoidal resistance is dependent on the contraction of hepatic stellate cells (HSC) around sinusoidal endothelial cell (SEC) through paracrine cross-talk of vasoconstrictor and vasodilator agents. Hydrogen sulfide (H2S), a recently discovered gas neurotransmitter, is a putative vasodilator whose role in hepatic vascular regulation and portal hypertension is unexplored. Four-week bile duct-ligated (BDL) rats with cirrhosis and control rats were treated daily with NaHS (56 micromol/kg) for 5 days. Isolated livers were perfused first with NaHS for 20 minutes and then with norepinephrine (NE) and the intrahepatic resistance studied. In normal rats and animals with cirrhosis, administration of NE resulted in a dose-dependent increase of portal pressure. This effect was attenuated by H2S treatment (P < .05). The H2S-induced relaxation of hepatic microcirculation was attenuated by glibenclamide, an adenosine triphosphate (ATP)-sensitive K+ channel inhibitor. L-Cysteine, a substrate of cystathionine-gamma-lyase (CSE), decreased vasoconstriction in normal rat livers (P < .05) but failed to do so in livers with cirrhosis. BDL resulted in a downregulation of CSE mRNA/protein levels and activity (P < .05). Our in vitro data demonstrate that CSE is expressed in hepatocytes, HSCs, but not in sinusoidal endothelial cells (SEC). HSC activation downregulates CSE mRNA expression, resulting in a defective production of H2S and abrogation of relaxation induced by L-cysteine. In conclusion, CSE-derived H2S is involved in the maintenance of portal venous pressure. The reduction of CSE expression in the liver with cirrhosis contributes to the development of increased intrahepatic resistance and portal hypertension.

Mechanisms Involved in the Contraction of Intrahepatic Portal Vein Branches by Clomipramine and Oxethazaine in Isolated Perfused Rat Livers

Clomipramine (CLM) and oxethazaine (OXZ) were previously reported to increase portal pressure by contracting portal vein branches (PVBs) in isolated perfused rat liver. In the present study, to characterize the contractile mechanisms, the effects of Y27632, HA1077, staurosporine, papaverine, SKF96365, and sulindac sulfide on the portal pressure increase induced by CLM and OXZ were examined comparatively with those induced by endothelin-1. The results suggest that 1) intrahepatic PVBs employ a Rho-kinase-dependent pathway for sustained contraction, 2) CLM contracts PVBs by activating a Rho-kinase pathway and Ca2+-channels, and 3) OXZ acts primarily by promoting Ca2+ entry through its ionophore-like action.

Postprandial splanchnic haemodynamic changes in patients with liver cirrhosis and patent paraumbilical vein

The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.

Re‐Evaluation of a Portocaval Venograft Without an Ameroid Constrictor as a Method for Controlling Portal Hypertension After Occlusion of Intrahepatic Portocaval Shunts in Dogs

To evaluate the use of a portocaval venograft without an ameroid constrictor in the surgical management of intrahepatic portosystemic shunts (PSS). Prospective clinical study. Seven dogs with intrahepatic PSS. Portal pressure was measured after temporary suture occlusion of the intrahepatic PSS. In dogs with an increase in portal pressure > or =8 mm Hg or signs of portal hypertension, a single extrahepatic portocaval shunt was created using a jugular vein. Clinical outcome and complications were recorded. The mean (+/-SD) portal pressure increased from 5.9+/-1.6 to 17.9+/-4.1 mm Hg with PSS occlusion. There were no intraoperative complications and, after creation of the portocaval shunt, the intrahepatic PSS could be completely ligated in all dogs. The final portal pressure was 9.6+/-1.9 mm Hg. Complications developed during postoperative hospitalization in 5 dogs and included incisional discharge (4 dogs), ascites (3), ventricular premature contractions (2), and melena, bloody diarrhea, neurologic signs, coagulopathy, and aspiration pneumonia (each in 1 dog). Six dogs died or were euthanatized with clinical signs related to depression, inappetance, abdominal pain, vomiting, melena, and abdominal distention, with a median survival of 82 days (range, 20-990 days). One dog was clinically normal at 33 months after surgery. Clinical signs observed in 6 dogs after surgery were consistent with portal hypertension. Use of a portocaval venograft without an ameroid constrictor may reduce the likelihood of hepatic vascular development, thereby increasing the risk of life-threatening portal hypertension should the venograft suddenly occlude. Use of a portocaval venograft without an ameroid constrictor to control portal hypertension after ligation of an intrahepatic PSS cannot be recommended.

Review article: a critical comparison of drug therapies in currently used therapeutic strategies for variceal haemorrhage.

Vasoactive drugs are safe and easy to administer, and universal treatment is the first-line approach for all patients with suspected variceal bleeding. There are strong arguments that the combination of vasoactive drugs, started as soon as possible, and endotherapy later on is the best therapeutic option, particularly in cases of ongoing bleeding at the time of endoscopy. The main action of vasoactive drugs is to reduce variceal pressure. This can be achieved by diminishing the variceal blood flow and/or by increasing resistance to variceal blood flow inside the varices. Changes in variceal pressure parallel changes in portal pressure. Drugs for the treatment of variceal bleeding can therefore be assessed by measuring the changes in portal pressure, azygos blood flow and variceal pressure. Vasoactive drugs can be divided into two categories: terlipressin (Glypressin), and somatostatin and its analogues, especially octreotide. Terlipressin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in the control of variceal haemorrhage and improves mortality. It is beneficial when combined with sclerotherapy. It also has the advantage that it might preserve renal function, one of the most important factors affecting the outcome of cirrhosis. As such, terlipressin is the most potent of the various vasoactive drugs. Somatostatin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in controlling variceal haemorrhage, and improves the success of sclerotherapy. The effect of octreotide is well established for preventing the increase in portal pressure after a meal (similar to blood in the intestines) though the effect of ocreotide on variceal pressure is controversial.