Use of color Doppler EUS in assessing azygos blood flow for patients with portal hypertension.

BACKGROUND: Azygos blood flow is an index of blood flow through gastroesophageal collateral vessels and varices in portal hypertension. Conventional measurement of azygos blood flow involves catheterization of the azygos vein. We studied the feasibility of assessing azygos blood flow with color Doppler endosonography and of monitoring the effects of vasoactive agents on azygos blood flow. METHODS: Patients with portal hypertension were examined by means of linear array color Doppler endoscopic ultrasonography (EUS). Patients who had taken propranolol or nitrates in the 4 weeks before the day of measurement of azygos blood flow were excluded. After identification of the azygos vein and recording of baseline readings of mean arterial blood pressure, pulse rate, and azygos blood flow, patients were selected in a random manner to receive a bolus injection of 2 mg terlipressin, 250 microg somatostatin, or saline solution (control). Azygos blood flow was measured 1, 5, and 10 minutes after injection (AzBF-1, AzBF-5, AzBF-10). RESULTS: Six patients were recruited in each treatment group. Basal azygos blood flow showed a positive association with the Child-Pugh grade of cirrhosis (p < 0.005). After bolus injection of terlipressin and somatostatin, there was a marked decrease in AzBF-1 (24% and 37%), AzBF-5 (42% and 19%), and AzBF-10 (40% both) compared with baseline. The control group showed no significant change in azygos blood flow. CONCLUSIONS: Color Doppler EUS is useful in assessing azygos blood flow in portal hypertension and in monitoring the effects of vasoactive agents.     

Effects of metoclopramide and domperidone on azygos venous blood flow in patients with cirrhosis and portal hypertension

The effects of pharmacological manipulation of the lower esophageal sphincter pressure on the esophageal circulation in patients with cirrhosis and portal hypertension were investigated in 33 patients by measuring the azygos venous blood flow, which is an index of blood flow through esophageal varices and periesophageal collaterals draining into the azygos venous system. Measurements were performed in baseline conditions and after the blind administration of metoclopramide (20 mg i.v.) (12 patients), domperidone (10 mg i.v.) (12 patients) and placebo (9 patients). Both metoclopramide and domperidone caused a significant reduction of azygos blood flow, that decreased by 11.5% (p less than 0.01) and 15.6% (p less than 0.02) respectively, while no change was observed in patients receiving placebo (+1.4%, not statistically significant). Reduction of azygos blood flow represents a selective effect of metoclopramide and domperidone on the esophageal circulation, since portal pressure, hepatic blood flow, cardiac output, heart rate and arterial blood pressure were unchanged by the administration of metoclopramide, domperidone or placebo. These results indicate that the administration of drugs that increase the lower esophageal sphincter pressure may reduce the inflow of blood into the esophageal varices in cirrhotic patients with portal hypertension.     

Measurement of azygos venous blood flow in the evaluation of portal hypertension in patients with cirrhosis. Clinical and haemodynamic correlations in 100 patients

Blood flow in the azygos vein, an index of blood flow through gastro-oesophageal collaterals, was measured by continuous thermal dilution in 100 patients with cirrhosis. Azygos blood flow was directly related to portal pressure (r = 0.54, P less than 0.001). Patients with portal hypertension had very high azygos blood flow (692 +/- 32 ml/min) in comparison with controls (n = 11, 174 +/- 29 ml/min). Patients with previous oesophageal bleeding had similar azygos blood flow as those without, but azygos blood flow was significantly greater in patients with massive or recurrent bleeding than in those with less severe haemorrhage, suggesting that the magnitude of collateral flow may influence the course of variceal bleeding. Patients with grade III varices had higher azygos blood flow than those with grades II or I. In addition, both oesophageal tamponade and vasopressin infusion, procedures of known value in variceal bleeding, markedly reduced azygos blood flow (-40% and -25%, respectively). Measurement of azygos blood flow allows evaluation of haemodynamic changes in the oesophageal collaterals of patients with portal hypertension, and provides useful information on the effect of therapeutic procedures aimed at arresting or preventing variceal haemorrhage.     

Protein content of liver lymph in patients with portal hypertension secondary to hepatic cirrhosis.

Protein content of liver lymph was measured in 14 patients with portal hypertension secondary to advanced hepatic cirrhosis. An abnormally low concentration was found in each patient, averaging 52% of plasma levels. This finding reflects a decreased sinusoidal permeability to protein, the possible effect of "capillarization of the sinusoid" and may bear on development of portal congestion.     

Blood flow and blood oxygen partial pressure of the azygos vein in portal hypertension evaluated by the catheter method

To evaluate the clinical significance of blood flow in the azygos vein and the oxygen partial pressure in azygos venous blood in portal hypertension, we examined 25 patients with liver cirrhosis, 4 with chronic hepatitis, 4 with idiopathic portal hypertension (IPH) and 16 controls by the continuous thermodilution method and azygos venous blood sampling. The azygos venous flow was significantly higher in the patients with chronic liver diseases than in the controls. There was a significant correlation between azygos venous flow and hepatic venous pressure gradient. In the patients with liver cirrhosis, about one half of the azygos venous flow was assumed to represent upward collateral flow, as the azygos venous flow was 3.4% of cardiac output in the controls, 6.3% in the liver cirrhosis patients, and 5.1% in the IPH patients. Oxygen partial pressure in azygos venous blood was higher in patients with portal hypertension, especially in the IPH patients, which indicates that part of splenic flow drains into the azygos vein.     

Peripheral blood cell variations in cirrhotic portal hypertension patients with hypersplenism

ObjectiveTo explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism.MethodsClinical data of 322 hypersplenism patients with decreased peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years.ResultsIn 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC + PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%); in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher (P<0.05).ConclusionsOf portal hypertensive patients with splenomegaly and hypersplenism, 64% have simultaneous decrease in various blood cells, 36% have decrease in single type blood cells, 52% of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.     

Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat.

Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation.     

Changes in gastrointestinal lymph and blood vessels in patients with cirrhotic portal hypertension

Background. The aim of this study was to characterize the lymph vessels in different parts of the gastrointestinal tract and also to evaluate morphometric changes in these vessels during cirrhotic portal hypertension. Methods. Sixteen patients with cirrhotic portal hypertension and 18 control subjects without portal hypertension were enrolled in the study. Tissue specimens were collected at autopsy or surgery, and were stained enzyme histochemically, using 5′-nucleotidase and alkaline phosphatase to distinguish lymph vessels and blood vessels, respectively. The numbers of vessels and their luminal areas were estimated using computer graphics software (National Institutes of Health [NIH] image program). Results. The numbers and luminal areas of the lymph vessels varied considerably among the different organs of the gastrointestinal tract, both in controls and in the patients with cirrhotic portal hypertension. There was no significant difference in the numbers of lymph vessels between controls and patients with cirrhotic portal hypertension. However, the luminal area of the lymph vessels in the esophagus and stomach was significantly greater in the patients with cirrhotic portal hypertension than in the controls. These differences in lymph vessels were not seen in the small intestine and colon. Conclusions. These data indicate that dilatation of lymph vessels may be related to the absorption of excess interstitial fluid, resulting from congestion, in cirrhotic portal hypertension. Received: November 30, 2000 / Accepted: April 13, 2001     

Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension

BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow measurements by means of the Doppler technique. The aim of the study was to evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS: Measurements of azygos blood flow by EUS and by the thermodilution technique were compared in 20 patients with portal hypertension. The ability of EUS flowmetry to detect changes in the azygos and portal venous flow after an intravenous dose of 2 mg of terlipressin was evaluated in 13 of the patients in a double-blind, randomized, placebo-controlled, cross-over design. RESULTS: The EUS Doppler and thermodilution measurements correlated significantly (R=0.81, P < 0.001). The azygos blood flow was found to be 14% higher by the EUS method than by thermodilution. The coefficient of variation of the EUS Doppler measurements of the azygos blood flow was 14.8%. After administration of terlipressin, the azygos blood flow, as measured by EUS Doppler, decreased significantly by 23% from 915 to 704 ml/min (P = 0.014) and the portal venous flow decreased by 28% from 1170 to 789 ml/min (P = 0.03). No effects of placebo were detected. CONCLUSIONS: These results show that EUS measurement of the azygos blood flow correlate strongly to the measurements by the thermodilution technique, and EUS is moreover well tolerated by the patients. The method is applicable for monitoring pharmacological effects on the superior porto-systemic collateral circulation and portal venous flow in patients with portal hypertension.     

Factors influencing development of portal hypertensive gastropathy in patients with portal hypertension.

Portal hypertensive gastropathy (PGP) is an important cause of bleeding in portal hypertension patients. Although hyperdynamic congestion seems to be the underlying mechanism, the factors that influence the development of PGP are not understood. To investigate these, 107 patients [cirrhosis, 35; noncirrhotic portal fibrosis (NCPF), 24; extrahepatic portal vein obstruction (EHPVO), 46; Budd-Chiari syndrome, 2] were prospectively studied. Eighty-three patients had Child's A, 17 had Child's B, and 7 had Child's C liver disease. Before sclerotherapy, although intravariceal pressure was similar, 4 cirrhosis patients (3.7%) but no NCPF or EHPVO patients had PGP. After sclerotherapy, 21 additional patients (20.3%) developed PGP during a follow-up of 23.2 +/- 3.4 months (range, 1-52). The incidence of PGP was higher in cirrhotic patients (37.1%) than in NCPF (16.7%; P less than 0.05) or EHPVO (8.7%; P less than 0.01) patients. The probability of developing PGP among all patients at the end of 52 months of follow-up was 30%, more in cirrhosis than in EHPVO (55% vs. 15%; P less than 0.005). Only 2 patients bled from PGP during follow-up. Development of PGP correlated with severity of liver disease, being more common in Child's C than Child's A patients (87% vs. 13%; P less than 0.001). PGP was seen more often in patients with gastroesophageal varices than in patients with esophageal varices alone (42% vs. 11%; P less than 0.01). In conclusion, the results show that development of PGP is significantly influenced by sclerotherapy, severity of liver disease, etiology of portal hypertension, coexisting gastric varices and is not directly correlated with intravariceal pressure.     

Effect of cholestyramine on bile acid kinetics in patients with portal cirrhosis of the liver

The kinetics of cholic acid (C) and chenodeoxycholic acid (CD) were studied in six patients with portal liver cirrhosis. The studies were conducted both before and after 5–6 weeks of treatment with cholestyramine (12 g/day). In keeping with previous observations, the pool size and formation of C showed subnormal values during the pretreatment period, while the production of CD was within normal limits. The pool sizes of C and CD did not change upon treatment with cholestyramine, but the mean total bile acid formation increased by a factor of about 2.5. The ratio between the amounts of C and CD synthesized remained essentially unchanged. Considering the therapeutic response previously observed in normal subjects and in patients with hyper-β-lipoproteinemia, the present results suggest a selective impairment of the biosynthesis of C in patients with portal liver cirrhosis. It is suggested that the primary defect may reside in the 12α-hydroxylase enzyme system.     

Mineralocorticoid escape in patients with compensated cirrhosis and portal hypertension.

Failure to escape from mineralocorticoids in compensated cirrhosis is considered a major argument supporting the overflow theory of ascites. To assess the frequency and mechanism of mineralocorticoid escape in cirrhosis, 9-alpha-fluorohydrocortisone (0.6 mg/day) was administered to 19 patients with compensated cirrhosis, portal hypertension, and no history of ascites who were able to maintain sodium balance on a 250 mmol Na+ diet. Fifteen patients (78.9%) escaped from mineralocorticoids, while 4 patients (21.1%) did not escape and developed ascites. Patients who did not escape had significantly higher cardiac index (4.97 +/- 0.42 vs 3.46 +/- 0.21 L.min-1.m-2) and lower peripheral vascular resistance (485.9 +/- 37.5 vs. 665.8 +/- 32.9 dyne.s.cm-5/m2) than those who escaped. Hepatic venous pressure gradient was not significantly different. The escape phenomenon was associated with a significant increase in mean arterial pressure, creatinine clearance, and atrial natriuretic factor and suppression of plasma renin activity. All of these parameters showed minimal or no changes in patients who did not escape. These results indicate that failure to escape from mineralocorticoids is uncommon in patients with compensated cirrhosis, is related to an inadequate expansion of effective plasma volume due to the accumulation of ascites, and occurs in patients with marked peripheral arteriolar vasodilation.     

Colonic wall thickening in patients with cirrhosis and portal hypertension.

OBJECTIVE: To determine the prevalence of colonic wall thickening (CWT) and its relation with other clinical and radiological findings of portal hypertension. EXPERIMENTAL DESIGN: Retrospective observational study. The follow-up period was at least 1 year. The colon wall was considered to be thickened when it measured > 6 mm. SUBJECTS: The study included 63 patients, what were admitted in Liver Unit of University and General Hospital of Alicante with hepatic cirrhosis who had an abdominal CT scan performed between March 1996 and December 1998. RESULTS: 21 (33.3%) patients showed CWT. This finding was particularly associated with the presence of collateral circulation [ OR = 10.3(1.5-100.8)] and portal thrombosis [OR = 12.8(1.4-118.4)] p<0.05. Patients with CWT tended to develop spontaneous bacterial peritonitis (CWT 14.3% vs no CWT 4.8%) [RR = 3(0.5 -16.6)] but this did not reach statistical significance (p= 0.18). CONCLUSIONS: A third of the patients with cirrhosis and portal hypertension present colonic wall thickening. This finding is related to radiological features and clinical consequences of portal hypertension.     

Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.     

The intracorporeal autoorganic biofilter of portal blood in portal hypertension surgery.

BACKGROUND/AIMS: The authors present the new surgical treatment method for portal hypertension by means of intracorporeal autoorganic biofilter of portal blood at the portosystemic shunt pathway. The hepatized spleen is used as the organic biofilter of portal blood. METHODOLOGY: The experiments were carried out on 20 mongrel dogs, both sexes, 18-20 kg of body weight. The animals were divided into the four equal groups. The comparative evaluation of portal hypertension treatment efficiency by means of several vascular portosystemic shunts were performed after the portal hypertension modeling. On the animals of groups I and II, the mesenterico-caval and splenorenal shunts were performed, respectively. The hepatized autospleen was involved in the portosystemic shunt pathway in the animals of group III. The animals of group IV served as controls. RESULTS: The reduction in perfusional pressure of the blood which flows to the liver led to damage of the organ's functional possibilities, significant disturbances to the hemodynamics and reduction of the liver detoxification possibilities, respectively, for several portocaval shunt creations during the portal hypertension model. On the other hand, the undetoxificated portal blood entrance into the system blood flow via the created shunt over the liver increased. CONCLUSIONS: The hepatized autospleen insertion into the portosystemic bloodflow gave us the opportunity to perform the dosage passing of portal blood into the systemic bloodflow and to maintain the pressure of the portal blood, which flows to the liver. Moreover, the hepatized autospleen has shown such specific liver functions as glucogenesis, albumin synthesis and others.