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Background: Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL)., Methods: Fourteen days after the operation, the rats were divided into without- and with-bleeding groups. Three series of PVL rats were used to investigate (i). the haemodynamic effects of glypressin (0.07 mg x kg(-1) intravenously), (ii). COX-1/COX-2 mRNA expression over abdominal aorta and superior mesenteric artery and (iii). plasma levels of 6-keto-prostaglandin-F1alpha. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was re-infused before blood and vessel sampling or the administration of glypressin., Results: Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage-transfused PVL rats with enhanced COX-1 expression of superior mesenteric artery and increased plasma levels of 6-keto-prostaglandin-F1alpha. There were no differences in the COX-2 expression of superior mesenteric artery and COX-1 and COX-2 expressions of abdominal aorta between without- and with-bleeding groups., Conclusion: In portal hypertensive rats with acute haemorrhage, COX-1 over-expression in the superior mesenteric artery plays a role in mediating the splanchnic hyposensitivity to glypressin.

Objectives: Terlipressin reduces portal pressure in cirrhotic patients mainly through intense splanchnic vasoconstriction that decrease portal venous inflow. Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1-adrenoceptor antagonist) has also been proposed to decrease portal pressure in cirrhotic patients possibly through a decrease in the intrahepatic vascular resistance. The current study was aimed to evaluate whether a combination of prazosin and terlipressin exerts more beneficial effects than terlipressin alone., Methods: Patients were randomly assigned to receive either a placebo (n = 12) or an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after prazosin or placebo, and 30 min after terlipressin., Results: Placebo administration did not affect any hemodynamic values. Terlipressin administration, on the other hand, resulted in expected changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic hemodynamics. In contrast, prazosin significantly decreased hepatic venous pressure gradient with an increased hepatic blood flow and intrinsic hepatic clearance. After terlipressin administration, a further decrease in hepatic venous pressure gradient was observed with preservation of hepatic blood flow and intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure gradient was more profound in patients receiving prazosin plus terlipressin than in those receiving terlipressin alone. However, the magnitude of changes in systemic hemodynamics was no different between the two groups of patients., Conclusions: The current study showed that a combination of prazosin and terlipressin resulted in a more profound reduction of hepatic venous pressure gradient with a preservation of hepatic blood flow and intrinsic hepatic clearance than did terlipressin alone. However, the combined therapy did not modify the systemic hemodynamic effects exerted by terlipressin.

Portopulmonary hypertension is now recognized as one of the pulmonary complications of chronic liver disease. However, previous studies reported that the incidence ranged from 0.25% to 2%, excluding fortuitous coincidence. In this study, we aimed to determine the variant hemodynamic and clinical features of portopulmonary hypertension in an area with a high prevalence of viral cirrhosis. After reviewing the hemodynamic data of 322 patients with portal hypertension admitted to the Taipei Veterans General Hospital between 1987 and 1999, we found 10 with portopulmonary hypertension. The overall incidence was, therefore, 3.1% in all patients with portal hypertension. Most of the patients with portopulmonary hypertension experienced exertional dyspnea. The survival times ranged from 2 to 86 months. In our series, most of the patients who died, died of complications related to cirrhosis and portal hypertension, but not of complications related to pulmonary hypertension. This study suggested that portopulmonary hypertension was not a frequent complication in cirrhotic patients and was not associated with an adverse outcome.

Background: Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status., Methods: Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (approximately 25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin., Results: As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05)., Conclusions: Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity.

1. Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding.2. Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 mg/kg) or aminoguanidine (70 mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine.3. Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P<0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P>0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P<0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P>0.05).4. Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.

Background: Octreotide and prazosin are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the haemodynamic effects of octreotide and prazosin, alone or in combination, in portal hypertensive rats., Methods: Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups-vehicle group (saline, 0.5 mL 12 h-1), octreotide group (30 micrograms kg-1 12 h-1), prazosin group (0.4 mg kg-1 12 h-1), and octreotide (30 micrograms kg-1 12 h-1) plus prazosin (0.4 mg kg-1 12 h-1) group-with eight rats in each group. Prazosin or saline was administered by gavage, whereas octreotide was administered by subcutaneous injection. The drug was given on the day of ligation and continued for 8 consecutive days. Systemic as well as splanchnic haemodynamic parameters were measured thereafter., Results: Portal vein-ligated rats exhibited typical hyperdynamic state compared with sham-operated rats. The portal venous pressure, portal tributary blood flow and cardiac index were significantly reduced by treatment of octreotide, prazosin or octreotide plus prazosin in portal hypertensive rats. Hyperdynamic parameters of systemic, renal and portal territory vascular resistances, and renal as well as hepatic arterial blood flow were ameliorated by treatment of octreotide or octreotide plus prazosin in portal hypertensive rats. Overall, octreotide treatment exerted more beneficial haemodynamic effects than prazosin treatment. The combination of octreotide and prazosin exerted better haemodynamic effects in cardiac index but worse effects in systemic as well as portal territory vascular resistance than octreotide treatment alone.

Portal hypertension (PHT) is characterized by increased portal pressure caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and specific ET receptors in maintaining the vasculopathy of PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated. ET receptor expression was determined in the superior mesenteric artery of sham and PHT rats by in situ autoradiography, radioligand binding analysis, and reverse-transcription polymerase chain reactions (RT-PCR). The pressor response to ET-1 was determined in vitro using isolated vascular rings and in vivo by measuring mean arterial pressure, splanchnic blood flow, and portal venous pressure following treatment with ET and selective ET receptor antagonists. The pressor response to ET in vitro was significantly enhanced in PHT concomitant with increased ET-A and ET-B receptor expression. There was a significant increase in the peak pressor response to ET (10 microg/kg intravenously) in portal hypertensive rats without any significant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 microg/kg intravenously). In contrast, ET-B receptor blockade with IRL-1038 (200 microg/kg intravenously) preferentially decreased splanchnic blood flow and portal venous pressure in portal hypertensive rats. These data suggest that enhanced ET-B receptor expression in portal hypertensive vessels contributes to the maintenance of elevated portal pressure in these animals.

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

Background/aims: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administration of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats., Methods: Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as controls. There were four animal groups for this study: portal vein ligation-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) group, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dinitrate (5 mg x kg(-1) x 12 h(-1) was given by gavage for 8 days starting 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement., Results: Contractile responses to KCI (15-90 mM) and phenylephrine (10(-9)-10(-4) M) were recorded. Both vascular reactivity and sensitivity were significantly reduced in portal vein ligation rats as compared to Sham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contractile responses to KCl and phenylephrine were significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate treatment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats., Conclusion: Our results show that long-term administration of isosorbide dinitrate enhanced vascular contractility in both portal vein ligation and Sham rats, but relative hyporeactivity persisted in portal vein ligation rats.

Octreotide and propranolol are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the hemodynamic effects of octreotide and propranolol, alone or in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 ml/day), octreotide group (100 microg/kg/12 hr), propranolol group (30 mg/kg/day), and octreotide (100 microg/kg/12 hr) plus propranolol (30 mg/kg/day) group. Propranolol or saline was administered by gavage, octreotide by subcutaneous injection. Drug was given one day before ligation and continued for eight consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by octreotide, propranolol, or octreotide plus propranolol in portal hypertensive rats. Portal territory, systemic, and renal vascular resistances were significantly enhanced, while hepatic arterial blood flow significantly reduced, in the octreotide and octreotide plus propranolol groups as compared to vehicle group. Our results showed that eight-day administration of octreotide, propranolol, or octreotide plus propranolol led to portal hypotensive and antihyperdynamic effects in portal hypertensive rats. Overall, octreotide treatment alone resulted in better antihyperdynamic profiles than propranolol treatment alone. The combination of octreotide and propranolol offered no therapeutic benefits and was slightly less effective than octreotide alone.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to enhanced production of vasodilator substances. Enhanced vasodilation and increased splanchnic blood flow contribute to the elevated portal pressure characteristic of PHT. The aim of this study was to determine whether cyclooxygenase (Cox) expression is altered in PHT vessels and whether chronic inhibition of this enzyme impacts on splanchnic blood flow in PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham operated. Plasma 6-keto-PGF1alpha (prostaglandin F1alpha) levels were significantly elevated in PHT after 2 days as compared with sham and remained elevated up to day 15. Treatment with indomethacin (2 mg/kg i.p. daily for 15 days) resulted in a significant decrease in 6-keto-PGF1alpha levels, which was concomitant with a significant decrease in superior mesenteric artery blood flow (Qsma) after 15 days in PHT rats. Cox-I expression was differentially enhanced in the PHT superior mesenteric artery and thoracic aorta during the development and progression of PHT. In contrast, Cox-II messenger RNA (mRNA) and protein expression was not detected in either of these vessels throughout the development of PHT. These data suggest that PHT is associated with enhanced Cox-I expression within the splanchnic vasculature concomitant with elevated plasma prostacyclin levels and a significant pressor response to indomethacin in PHT animals. We conclude that enhanced Cox-I expression results in increased prostacyclin levels that partially contribute to the maintenance of the hyperemia typical of PHT.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-alpha and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-alpha and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-alpha and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/ nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-alpha (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-alpha and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. The reasons for the decreased resistance include an increased responsiveness to a vasodilator substance. Because the activation of an inhibitory guanine nucleotide regulatory (Gi) protein can result in endothelium-dependent relaxation, we tested the hypothesis that exaggerated Gi-protein induced relaxation via a nitric oxide (NO)-dependent pathway partly reflects the enhanced Gi-protein expression in PHT vessels. PHT was created in Sprague-Dawley rats by a partial portal-vein ligation. Control animals were sham operated. Using isolated vascular rings in the absence or presence of an intact endothelium, N(G)-nitro-L-arginine methyl ester (L-NAME), and pertussis toxin, dose response relationships for sodium fluoride (NaF; range, 0.1-4 mmol/L), a Gi protein activator, were determined in a cumulative manner. Gi-protein expression was determined by Western blotting. NaF caused a dose-dependent relaxation in both sham and portal hypertensive pre-contracted vessels, an effect that was significantly inhibited by pertussis toxin, endothelial denudation, and L-NAME. Concentrations of NaF greater than 4 mmol/L caused contractions, an effect that was unaffected by L-NAME. The NaF-induced relaxation response was significantly greater in PHT vessels as compared with sham concomitant with increased Gi-protein expression in PHT vessels. These data suggest that the enhanced endothelial Gi-protein-induced relaxation in PHT vessels may partly reflect enhanced expression of Gi-proteins in PHT vessels and may, thus, represent an important mechanism for exaggerated NO-dependent relaxation in the PHT vasculature.

Background: Despite many attempts to create esophageal varices in experimental animals, most of them have failed. This study investigated whether rats with partial portal vein ligation (PVL) and left adrenal vein ligation (LAL) develop hyperdynamic circulation and dilated esophageal submucosal veins as compared with sham-operated (Sham) plus LAL rats., Methods: Two series of experiments were performed to measure (a) systemic and portal hemodynamics and (b) the cross-sectional area of esophageal submucosal veins in Sham, PVL, Sham plus LAL, and PVL plus LAL rats. Hemodynamic studies with a thermodilution technique and esophageal morphometric analyses were performed 14 days after the operation., Results: PVL rats with or without LAL had a significantly lower mean arterial pressure and systemic vascular resistance accompanied by a significantly cardiac index and portal pressure than Sham rats with or without LAL (P < 0.05). LAL did not induce changes in mean arterial pressure, cardiac index, systemic vascular resistance, hear rate, or portal pressure in either Sham or PVL rats (P > 0.05). The mean cross-sectional area of esophageal submucosal veins in PVL rats with LAL (7340 +/- 833 microns2) was significantly larger than that in Sham rats with LAL (4236 +/- 556 microns2; P < 0.05). There was no significant difference in the mean cross-sectional area of esophageal submucosal veins between PVL and Sham rats without LAL., Conclusions: PVL rats with LAL developed hyperdynamic circulation similar to PVL rats without LAL. In addition, PVL plus LAL rats had larger esophageal submucosal veins than Sham plus LAL rats. This study shows that the esophageal submucosal veins of the 14-day partially portal vein-ligated rats with LAL resemble the structural abnormalities observed in human esophageal varices, suggesting that this model could be useful to investigate this entity.

Propranolol is used clinically as a prophylactic drug to prevent oesophageal variceal bleeding in cirrhotic patients with portal hypertension. Vascular hyporesponsiveness is a common characteristic of the portal hypertensive state. The present study aimed to investigate whether chronic administration of propranolol could improve vascular responsiveness in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls. There were four study groups: PVL-propranolol group (portal hypertensive rats receiving propranolol), PVL-vehicle group (portal hypertensive rats receiving saline), sham-propranolol group (sham-operated rats receiving propranolol) and sham-vehicle group (sham-operated rats receiving saline). Propranolol (30 mg kg-1 day-1) or saline was given for 9 days via gastric gavage starting 1 day before ligation and thereafter. Then, the superior mesenteric artery was removed from each group for contractile study after haemodynamic measurement. In portal hypertensive rats, propranolol significantly alleviated the hyperdynamic state, including portal pressure, cardiac index and total peripheral resistance in the treated group compared with the vehicle group. The maximal contractile responses to KCl and vasopressin in mesenteric artery were significantly greater in the sham-vehicle group than in the PVL-vehicle group. Long-term propranolol treatment enhanced the contractile reactivity of mesenteric artery to KCl and vasopressin in PVL rats, and the contractile profiles were corrected towards those in sham-treated animals. In contrast, propranolol treatment decreased heart rate, mean arterial pressure and cardiac index but did not alter the contractile responsiveness of sham-operated rats. These results showed that, in portal vein stenosed rats, long-term treatment with propranolol improved arterial contractile reactivity together with portal pressure reduction. The propranolol effect on vascular reactivity is probably related to haemodynamic improvement, instead of a direct contractile effect on the vasculature.

A serotonin mechanism has been reported to contribute to the hyperdynamic circulation of portal hypertension. Different studies have demonstrated that serotonin antagonists decrease portal pressure in portal hypertensive patients and animals. The present study was undertaken to investigate the effect of AT-112, an analog of ketanserin, on portal hypertension induced by partial portal vein ligation in rats. Since ketanserin is known to possess alpha 1-adrenergic antagonistic activity, the effect of AT-112 was compared to that of prazosin. A single dose (prazosin 4.2 micrograms/kg, AT-112 1 mg/kg) was chosen to produce a similar hypotensive effect (-20 +/- 4% for prazosin and -24 +/- 4% for AT-112). At this dose, prazosin significantly decreased total peripheral resistance whereas AT-112 significantly decreased cardiac index and heart rate. Both agents significantly decreased the portal tributary blood flow and portal pressure. In rats receiving AT-112, a significant correlation was found between the magnitudes of decrease in cardiac index and the decrease in portal tributary blood flow. We also found that the magnitude of reduction in portal pressure was greater following AT-112 administration. This study suggested that AT-112 may have more beneficial hemodynamic effects than prazosin in portal hypertensive rats. Our results provide further support for the serotonergic mechanism in the pathogenesis of hyperdynamic circulation in portal hypertension.

The present study investigated plasma levels of interleukin-8 (IL-8) in patients with post-hepatitic cirrhosis and correlated it with the severity of liver diseases and haemodynamic parameters. Plasma IL-8 levels were significantly higher in 57 post-hepatitic cirrhotic patients (7.5 +/- 1.8 pg/mL; P < 0.005) than those in 41 healthy subjects (2.0 +/- 0.2 pg/mL). Elevated (> 5 pg/mL) plasma IL-8 levels were found in up to 30% of cirrhotic patients. In cirrhotic patients, plasma IL-8 levels progressively increased in relation to the severity of liver dysfunction (4.5 +/- 1.0, 4.9 +/- 1.4 and 20.5 +/- 8.3 pg/mL for Pugh's class A, B and C, respectively; P < 0.005). A significant correlation was observed between plasma IL-8 levels and serum bilirubin levels (r = 0.72; P < 0.001). There were no differences in the hepatic venous pressure gradient (15.4 +/- 1.1 vs 15.1 +/- 0.9 mmHg; P > 0.05) and systemic vascular resistance (1119 +/- 118 vs 1199 +/- 54 dyn.s/cm5; P > 0.05) between cirrhotic patients with and without elevated plasma IL-8 levels. In addition, plasma IL-8 levels did not correlate with hepatic venous pressure gradient (r = 0.26; P > 0.05) and systemic vascular resistance (r = -0.24; P > 0.05). These results demonstrate that plasma IL-8 levels are increased in patients with post-hepatitic cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of enhanced IL-8 levels. IL-8 does not play a role in the hyperdynamic circulation observed in patients with post-hepatitic cirrhosis.

Background: Colonic vascular ectasias and colorectal varices have been observed in patients with cirrhosis. However, the pathogenesis of these vascular lesions has not been established., Methods: We enrolled 35 cirrhotic patients and 20 normal controls in this study. All received colonoscopic examinations and measurements of plasma glucagon levels. Portal pressure measurements were performed in all the cirrhotic patients., Results: Colonic vascular ectasias occurred more commonly in cirrhotic patients than in controls (17 of 35 versus 0 of 20; p = 0.009) and more commonly in cirrhotic patients with ascites than in those without (15 of 24 versus 2 of 11; p = 0.038). However, the presence of colonic vascular ectasias was not related to the hepatic venous pressure gradient or plasma glucagon levels. Colorectal varices also occurred more commonly in cirrhotic patients than in controls (16 of 35 versus of 1 of 20; p = 0.034), but the hepatic venous pressure gradient, plasma glucagon levels, and severity of cirrhosis were not related to the presence of colorectal varices., Conclusions: Portal hypertension per se and increased plasma glucagon levels may not play an important role in the pathogenesis of colonic vascular ectasias or colorectal varices in patients with cirrhosis.

The hemodynamic effects of long-term administration of octreotide in portal hypertension has not been established. In addition, whether long-term octreotide treatment prevents the development of portosystemic shunts has not yet been evaluated. Hence, the current study was undertaken to evaluate the effects of long-term administration of octreotide in rats with portal vein stenosis. Immediately after portal vein stenosis or sham operation, rats were given either a long-term octreotide administration of 100 micrograms/kg or a placebo every 12 hours by subcutaneous injection for 14 consecutive days. Systemic hemodynamics and regional blood flows, degree of mesenteric-systemic shunts, and plasma glucagon concentrations were measured after the final dose of octreotide or placebo. A fifth group of portal vein-stenosed rats received hemodynamic and plasma glucagon measurements after 1-day octreotide treatment given at 14 days after surgery. Long-term octreotide treatment modified the hyperdynamic circulation without affecting the degree of mesenteric-systemic shunts, and 1-day octreotide treatment decreased portal tributary blood flow without affecting the portal pressure, systemic hemodynamics, and degree of mesenteric-systemic shunts. Plasma glucagon levels were decreased in portal vein-stenosed rats receiving either long-term or 1-day octreodtide compared with rats receiving placebo. In contrast, chronic octreotide treatment did not affect any of the hemodynamic values or plasma glucagon levels in sham-operated rats. In conclusion, long-term administration of octreotide modified in part the development of portal hypertension and hyperdynamic circulation in portal vein-stenosed rats without affecting the degree of mesenteric-systemic shunts.

The prevalence of gastric ulcer and its relationship to the severity of cirrhosis and degree of portal hypertension was evaluated in 245 cirrhotic patients, and compared with 245 age- and sex-matched healthy subjects. Portal and systemic haemodynamic studies were performed in cirrhotic patients. The prevalence of gastric ulcer in cirrhotic patients was 20.8%, which was significantly higher than the 4.0% found in healthy controls. Using a multivariate logistic regression model, the hepatic venous pressure gradient was found to be the only predictor of the prevalence of gastric ulcer in cirrhotic patients to present with gastric ulcer. The hepatic venous pressure gradient was significantly higher in cirrhotic patients with gastric ulcer than in those without (17.3 +/- 4.4 vs 15.5 +/- 5.0 mmHg, P = 0.01). Other variables, including sex, smoking, cardiac output and severity or aetiology of cirrhosis did not show significant differences between the two patient groups. The prevalence of gastric ulcer in cirrhotic patients whose hepatic venous pressure gradient was below 12 mmHg (4.5%) was similar to that observed in the healthy controls (4.0%). However, when the hepatic venous pressure gradient was > 12 mmHg, the prevalence of gastric ulcer (24.4%) was significantly higher than that in control subjects. However, the incidence of gastric ulcer was not related to the degree of portal hypertension. In conclusion, the prevalence of gastric ulcer in cirrhotic patients was found to be significantly higher than in the age- and sex-matched healthy subjects. Portal hypertension with a hepatic venous pressure gradient > 12 mmHg may be an important factor contributing to the increased prevalence of gastric ulcer observed in patients with liver cirrhosis.

Background: The prevalence of duodenal ulcer increases in cirrhotic patients. However, the pathogenesis remains unclear., Methods: The prevalence of duodenal ulcer and their relationship to cirrhosis and portal hypertension were evaluated in 325 cirrhotic patients, and compared with 325 age- and sex-matched healthy subjects. Portal and systemic hemodynamic studies were performed in all cirrhotic patients. Histological examination of gastric antral mucosa for Helicobacter pylori (H. pylori) was performed in 16 cirrhotic patients with duodenal ulcer and in 34 cirrhotic patients without duodenal lesions., Results: The prevalence of duodenal ulcer in cirrhotic patients was 9.5% (31 out of 325), significantly higher than 4.0% (13 out of 325) in the healthy controls (p = 0.007), but was not related to the severity of liver cirrhosis. The positive rate of H. pylori was not different between cirrhotic patients with duodenal ulcer and those without duodenal lesions (9/16 vs. 18/34, p > 0.05). The hepatic venous pressure gradient was also not different between these groups (17.2 +/- 5.1 vs. 16.1 +/- 4.9 mmHg, p > 0.05). Other variables including sex, smoking, and etiology of cirrhosis did not show significant differences., Conclusions: The prevalence of duodenal ulcer is significantly higher in cirrhotic patients than in the age- and sex-matched healthy subjects. The severity of cirrhosis, the presence of H. pylori or portal hypertension per se does not play an important role in the increased prevalence of duodenal ulcer in cirrhotic patients.

To determine the effect of endoscopic variceal sclerotherapy or ligation on portal hypertensive gastropathy, 90 cirrhotic patients with esophageal variceal bleeding were randomized to receive sclerotherapy (n = 44) or ligation (n = 46). Follow-up endoscopic observations of the gastric mucosa were recorded at 3-month intervals after variceal eradication. Clinical characteristics in both groups were similar. Probability for a change in the severity of portal hypertensive gastropathy was not related to method of eradication. Most cases of portal hypertensive gastropathy that changed in severity returned to baseline status with time, but the return was faster after ligation than after sclerotherapy. According to the results of multivariate analyses, sclerosant volume was the only factor associated with a significant difference between the group with static gastropathy (n = 15) and that with dynamic change in gastropathy (n = 23) after sclerotherapy. No relevant factors were found in the patients receiving ligation. We conclude that changes in the severity of portal hypertensive gastropathy after endoscopic variceal sclerotherapy or ligation are reversible. Most cases of gastropathy return to baseline status sooner or later.