Comparative study between nadolol and 5-isosorbide mononitrate vs. endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial.

BACKGROUND: After variceal bleeding, cirrhotic patients should receive secondary prophylaxis. AIM: To compare nadolol plus 5-isosorbide mononitrate (5-ISMN) with endoscopic band ligation. The end points were rebleeding, treatment failure and death. METHODS: One hundred and nine cirrhotic patients with a recent variceal bleeding were randomized: nadolol plus 5-ISMN in 57 patients and endoscopic band ligation in 52 patients. RESULTS: The mean follow-up was 17 and 19 months in nadolol plus 5-ISMN and endoscopic band ligation groups, respectively. No differences were observed between groups in upper rebleeding (47% vs. 46%), variceal rebleeding (40% vs. 36%), failure (32% vs. 22%), major complications (7% vs. 13.5%) and death (19% vs. 20%), respectively. The actuarial probability of remaining free of rebleeding, failure and deaths were similar in both groups. Time to rebleeding shows that endoscopic band ligation patients had an early rebleed, with a median of 0.5 month (95% CI: 0.0-4.2) compared with patients from nadolol plus 5-ISMN, 7.6 months (95% CI: 2.9-12.3, P < 0.013). Multivariate analysis indicated that outcome-specific predictive factor(s) for rebleeding was Child A vs. B + C (P < 0.01); for failure was Child A vs. B + C (P < 0.02); and for death ascites (P < 0.01) and rebleeding (P < 0.02). CONCLUSION: This trial suggests no superiority of endoscopic band ligation over nadolol plus 5-ISMN mononitrate for the prevention of rebleeding in cirrhotic patients.

Patients with ascites have higher variceal pressure and wall tension than patients without ascites.

OBJECTIVE: It has been suggested that ascites is a risk factor for variceal bleeding. Recently, it has been demonstrated that total paracentesis decreases variceal pressure. However, no data are available showing the basal variceal pressure in patients with and without ascites. METHODS: We studied 76 cirrhotic patients, 49 with and 27 without ascites. Variceal pressure was measured by direct puncture. Variceal size, variceal pressure gradient, and variceal wall tension were also obtained. RESULTS: No demographic differences were observed between the groups. Child score was higher (9.7+/-1.5 vs 7.8+/-2.1, p < 0.001) and serum albumin lower (2.6+/-0.6 vs 3.0+/-0.7 mg %, p < 0.02) in ascitic than in nonascitic patients, respectively. Variceal pressure and variceal pressure gradient were significantly higher in patients with ascites than in those without ascites (25.0+/-6 vs 20.4+/-4.6 mm Hg, p < 0.001 and 18.75+/-4.7 vs 13.70+/-4.1 mm Hg, p < 0.0001, respectively). The variceal wall tension was significantly higher in patients with ascites (71.0+/-25.1 mm Hg/mm) than in those without ascites (55.1+/-22.1 mm Hg/mm, p < 0.03). No relationship was observed between variceal pressure gradient and liver function. Ascites patients included in Child-Pugh grade A+B presented a similar variceal pressure to Child C patients (18.5+/-4.2 vs 19.3+/-5.7 mm Hg, respectively, p = ns). In addition, no relationship was observed between variceal pressure gradient and etiology of cirrhosis. CONCLUSION: Our results demonstrate that patients with ascites have significantly higher variceal pressure and wall tension than patients without ascites. These results suggest that patients with ascites may be at risk for variceal bleeding.

Efficacy of octreotide and sclerotherapy in the treatment of acute variceal bleeding in cirrhotic patients. A prospective, multicentric, and randomized clinical trial.

BACKGROUND: Sclerotherapy is the most widely used method for treatment of acute variceal bleeding. Previous reports have suggested that octreotide infusion is as effective as sclerotherapy. Our aim was to investigate the efficacy and safety of octreotide in comparison with sclerotherapy in controlling variceal bleeding. METHODS: Seventy-six cirrhotic patients were randomized to receive either sclerotherapy (n = 37) or octreotide (n = 39) infusion of 50 microg/h intravenously for 48 h after a bolus of 100 microg, followed by subcutaneous injection of 100 microg/8 h for an additional 72 h. RESULTS: The two groups were similar in base-line data. A similar initial control of bleeding was obtained in 94.6% for sclerotherapy and 84.6% for octreotide (NS). No difference was observed between sclerotherapy and octreotide in rebleeding (23% versus 33%) and treatment failure (22% versus 36%, respectively). Furthermore, the overall success of treatment was 78% for sclerotherapy and 64% for octreotide. No significant difference in mortality was observed between treatments (eight patients for octreotide and three patients for sclerotherapy, NS). CONCLUSIONS: These results show that both treatments present a very high and similar initial and final control of bleeding. However, there is a trend that could be clinically important towards better results in the patients treated with sclerotherapy.

Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients.

BACKGROUND/AIMS: Terlipressin decreases portal pressure. However, its effects on variceal pressure have been poorly investigated. This study investigated the variceal, splanchnic and systemic hemodynamic effects of terlipressin. METHODS: Twenty cirrhotic patients with esophageal varices grade II-III, and portal pressure > or =12 mmHg were studied. Hepatic venous pressure gradient, variceal pressure and systemic hemodynamic parameters were obtained. After baseline measurements, in a double-blind administration, 14 patients received a 2mg/iv injection of terlipressin and six patients received placebo. The same measurements were repeated 60 min later. RESULTS: No demographic or biochemical differences were observed in basal condition between groups. Terlipressin produced significant decreases in intravariceal pressure from 20.9+4.9 to 16.3+/-4.7 mmHg (p<0.01, -21+/- 16%), variceal pressure gradient from 18.9+/-4.8 to 13.5+/-6.0 mmHg (p<0.01, -28+/-27%), estimated variceal wall tension from 78+/-29 to 59+/-31 mmHg x mm (p<0.01, -27+/-22%), and hepatic venous pressure gradient from 19.4+/-4.5 to 16.8+/-5 mmHg (p<0.01, -14+/-12%) at 60 min. The change in variceal pressure after 60 min of terlipressin administration was greater than the change in wedge hepatic venous pressure (-4.7 mmHg vs -0.5 mmHg, respectively, p<0.0001). Terlipressin also caused significant decreases in heart rate and cardiac index and increases in mean arterial pressure and peripheral vascular resistance. CONCLUSIONS: Our results demonstrate that terlipressin produces significant and prolonged decreases in variceal pressure and variceal wall tension and has intrinsic effects on portal pressure and systemic hemodynamics. Variceal pressure provides a better assessment of the effects of terlipressin administration on esophageal varices than hepatic venous pressure gradient.

Variceal band ligation and variceal band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding in cirrhotic patients: a randomized, prospective and controlled trial.

BACKGROUND: The combination treatment of band ligation plus sclerotherapy has been proposed to hasten variceal eradication. The aim of this study was to assess the efficacy of band ligation alone versus band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding. METHODS: Eighty cirrhotic patients were randomized to group I (band ligation) with 41 patients or to group II (band ligation plus sclerotherapy) with 39 patients in whom polidocanol (2%) was injected 1 to 2 cm proximal to each band. RESULTS: At baseline, both groups were similar with regard to clinical, demographic and laboratory data. Mean follow-up time (standard error) for group I was 336.5 +/- 43.4 days and for group II 386.1 +/- 40.1 days (p = 0.4). No statistical differences were observed between group I and group II in relation to recurrence of bleeding (31.7% vs. 23%, p = 0.38), treatment failure (24.4% vs. 12. 8%, p = 0.18), death (39% vs. 30.8%, p = 0.44) and variceal eradication (65.8% vs. 74.4%, p = 0.40). Group II had a significantly higher number of complications than group I, 30.8% versus 7.3%, respectively (p = 0.05). The number of bleeding related deaths was higher in group I than in group II (22% vs. 10.3%, respectively; p = 0.15). CONCLUSIONS: No significant difference was observed between band ligation and band ligation plus sclerotherapy in prevention of recurrent variceal bleeding. Furthermore, there was a higher incidence of complications in the latter group.

Total volume paracentesis decreases variceal pressure, size, and variceal wall tension in cirrhotic patients.

It has been suggested that ascites is a risk factor for variceal bleeding in cirrhotic patients. However, no data of total volume paracentesis (TVP) effects on variceal hemodynamics has yet been published. The aim of this study was to investigate the effects of TVP on variceal pressure, size, and tension in cirrhotic patients. Before sclerotherapy, 18 cirrhotic patients with grade II esophageal varices were studied. The following measurements were performed on 12 patients at basal condition and after TVP: inferior vena cava pressure, esophageal pressure (EP), and intravariceal pressure (IVP) by direct punction and variceal size at endoscopy. The same measurements were performed at basal condition and 1 hour later without TVP on the other 6 patients used as a control group. Variceal pressure gradient (VPG) and variceal wall tension (WT) were calculated. Paracentesis and intra-abdominal pressure were obtained with a direct punction. No demographic differences were observed between both groups. Paracentesis produced a significant reduction of IVP (from 25.6 +/- 2.4 to 17.9 +/- 2.1 mm Hg, means +/- SEM, -30%, P < .05), VPG (from 16.6 +/- 2.4 to 10.8 +/- 1.4 mm Hg, -35%, P < .05). TVP also reduced variceal size (from 9 +/- 0.3 to 5.6 + 0.4 mm, -38%, P < .05) and WT (from 75.3 +/- 11.6 to 30 +/- 4.7 mm Hg. mm, -60%, P < .05). Intra-abdominal pressure decreased from 18 +/- 2.2 to 4 +/- 0.9 mm Hg (P < .05), and IVC decreased from 15.5 +/- 2.4 to 5.7 +/- 1.5 mm Hg (P < .05). No significant differences were observed in mean arterial pressure and heart rate. The mean ascitic fluid removed was 8 +/- 0.71 L. No significant difference between measurements was observed in the control group. Our results show that TVP significantly decreases variceal pressure and tension. These results suggest that ascites removal can be useful in the treatment of variceal bleeding in cirrhotic patients.

Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage.

BACKGROUND & AIMS: Uncontrolled studies suggest that placement of a transjugular intrahepatic portosystemic shunt (TIPS) could be useful in the treatment of variceal bleeding. The aim of this study was to evaluate the efficacy and safety of TIPS in the elective treatment of hemorrhage from esophageal varices in a randomized controlled study that compared the effects of TIPS with those of endoscopic sclerotherapy (ES). METHODS: Sixty-three consecutive cirrhotic patients with hemorrhage from esophageal varices were included. Thirty-two patients were randomly allocated to ES and 31 to TIPS groups. RESULTS: One patient in each group died before the therapeutic procedure could be performed. During a mean follow-up period of 15 months, variceal rebleeding occurred in 51.6% of the patients in the ES group and 23% of those in the TIPS group. Uncontrolled rebleeding occurred in 10 of 31 patients in the ES group, whereas rebleeding did not occur in any patient of the TIPS group. Hepatic encephalopathy was more frequent in TIPS patients (33.3%) than in those treated by ES (13%). However, mortality was similar in both treatment groups. CONCLUSIONS: These preliminary results suggest that TIPS is more effective than ES in the prevention of variceal rebleeding in cirrhotic patients, even though no difference in survival was observed.

Ultrasonographic diagnosis of acute alcoholic hepatitis 'pseudoparallel channel sign' of intrahepatic artery dilatation.

BACKGROUND: In an ultrasound pilot study of acute alcoholic hepatitis (AAH), parallel tubular structures within the liver subsegments were observed. Pulse-Doppler flowmetry revealed that these structures were formed by a dilated hepatic arterial branch and an adjacent portal venous branch. This finding was termed the "pseudoparallel channel sign" (PPCS). The aims of this study were to assess the significance of this sign and show the characteristic ultrasound findings of AAH. METHODS: PPCS was specifically searched for on ultrasonography by two physician operators in consecutive patients (77 AAH, 119 other alcoholic liver disease, 49 nonalcoholic liver disease, and 15 healthy patients). RESULTS: PPCS was observed in 90% of patients with AAH and in 23% of patients with other alcoholic liver disease. This sign was not detected in nonalcoholic liver disease or healthy patients. Biopsy specimens were available in 100 patients, 51 of whom were patients with alcoholism. In those 51 patients, PPCS gave a sensitivity of 82%, a specificity of 87%, and an accuracy of 84% in diagnosing AAH. Patients with criteria of AAH had more segments involved with PPCS than patients without. CONCLUSIONS: PPCS may be an important diagnostic finding in AAH.

Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites. Results of a randomized study.

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.

Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats.

Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4-induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol-treated rats had significantly lower cardiac output (-31%) and heart rate (-26%) than controls (p less than 0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 +/- 0.4 vs. 6.3 +/- 0.5 ml per min.100 gm in controls, p less than 0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 +/- 0.2 vs. 2.0 +/- 0.1 mmHg per ml per min.100 gm body weight (not significant)]. Hence, the fall in portal pressure (-19%) was expected from the decrease in portal inflow (-24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral vessels, since beta-blockade does not modify portal vascular resistance in cirrhosis.

Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin.

Equilibrium constants for the binding of protoporphyrin to serum albumin and hemopexin and liver cytosolic fatty acid-binding protein of the rat were determined fluorometrically. The experimental equilibrium constant [10(6) M-1 (mean +/- S.D.)] values were 8.4 +/- 1.3, 10.0 +/- 2.4 and 34.0 +/- 3.0 for albumin, hemopexin and liver fatty acid-binding protein, respectively. Statistical analysis showed the equilibrium constant of binding of protoporphyrin to liver fatty acid-binding protein to be significantly (p less than 0.01) higher than that to albumin and hemopexin. The data suggest that in patients with erythropoietic protoporphyria an equilibrium gradient may exist which favors the uptake by hepatocytes of plasma protoporphyrin as a result of its greater affinity for intracellular liver fatty acid-binding protein.

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis.

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (from 9.0 +/- 2.1 to 11.7 +/- 2.7 mmHg per liter per min, p less than 0.001), whereas mean arterial pressure did not change (77 vs. 78 mmHg). Propranolol significantly reduced hepatic artery blood flow (from 0.65 +/- 0.20 to 0.55 +/- 0.14 liters per min, p less than 0.01). However, reduction of hepatic artery blood flow (-12.9 +/- 7.3%) was significantly less than reduction of cardiac output (-21.1 +/- 5.2%, p less than 0.01). As a result, the fraction of the cardiac output delivered to the liver was significantly greater after propranolol (8.0 +/- 1.7%) than before (7.3 +/- 1.7%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting.

The present study investigated whether, in rats with portal hypertension due to cirrhosis of the liver induced by carbon tetrachloride, blood volume restitution following a hemorrhage produces an increase of portal pressure beyond control values, as observed in rats with prehepatic portal hypertension. Since carbon tetrachloride-induced cirrhosis caused mild portal-systemic shunting, in some of the cirrhotic rats (12 of 29 rats) portal-systemic shunting was enhanced by a transient (4 days) partial constriction of the portal vein, which was removed 1 week prior to the study. After baseline measurements of portal pressure and arterial pressure, 15 ml per kg of blood were withdrawn at a rate of 0.3 ml per min and reinfused 15 min later. After blood reinfusion, portal pressure and arterial pressure were measured again, and cardiac output, regional blood flows and portal-systemic shunting were determined using radioactive microspheres. Portal-systemic shunting was 78 +/- 11% of total blood flow in the cirrhotic rats that had temporary portal vein constriction, but only 5 +/- 2% (p less than 0.001) in those that did not. Blood volume restitution in low-portal-systemic shunting rats did not produce any significant modification in splanchnic or systemic hemodynamics. However, in rats with high portal-systemic shunting, blood volume restitution produced a significant increase in portal pressure (from 9.9 +/- 0.9 to 13.5 +/- 0.9 mmHg, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage.

This study evaluated the clinical application of a pressure-sensitive gauge that allows the noninvasive measurement of the pressure of esophageal varices at endoscopy. The study was performed in 70 patients with cirrhosis and portal hypertension. Among them, 47 had bled from the varices and 23 had varices but had not bled. In addition to measurements of variceal pressure, the size of the varices was estimated semiquantitatively at endoscopy. This allowed an estimate of the tension on the wall of the varices as the product of the transmural pressure and the estimated radius of the varices. Most patients had a standard hemodynamic evaluation of portal hypertension, with measurements of wedged and free hepatic venous pressures, and of azygos blood flow. These were performed within 24 h of the variceal pressure measurements. Variceal pressure was significantly higher in bleeders than in nonbleeders (15.7 +/- 2.8 vs. 12.1 +/- 2.6 mmHg, p less than 0.001) in spite of a similar portal pressure in both groups (20.1 +/- 5.1 vs. 20.4 +/- 7.6 mmHg, NS). More than 60% of the bleeders, but only 22% of the nonbleeders had a variceal pressure greater than or equal to 15 mmHg (p less than 0.005). Among nonbleeders, variceal pressure was higher in patients with large varices (13.9 +/- 2 mmHg, n = 9) than in those with small varices (10.9 +/- 2.4 mmHg, n = 14) (p less than 0.01). Estimates of variceal wall tension further exaggerated the differences between bleeders and nonbleeders (66.1 +/- 22.6 vs. 32.0 +/- 19.8 mmHg.mm, p less than 0.001). More than 50% of bleeders, but just 9% of nonbleeders had an estimated variceal tension greater than 50 mmHg.mm (p less than 0.001). Our findings support the role of an increased variceal pressure in the pathogenesis of variceal hemorrhage, and suggest that this noninvasive technique can be valuable in assessing the risk of variceal hemorrhage in patients with portal hypertension.

Diagnosis and evaluation of portal hypertension.

In the past recent years there have been several major innovations in the diagnosis and evaluation of portal hypertension. These include the application of new endoscopic, ultrasonographic and haemodynamic techniques that allow a better evaluation of the portal hypertensive patient, specially when prophylactic medical therapy is considered. Ultrasonography is very useful to assess the patency of the portal vein. The association of a pulsed Doppler flowmeter increases its accuracy and allows the non-invasive estimation of the direction and magnitude of portal blood flow. Endoscopic measurements of variceal pressure may help to understand the mechanism of variceal bleeding, and perhaps might permit to assess the risk of haemorrhage in the individual patient. In addition to the measurement of portal pressure, measurement of blood flow through the azygos vein has been the major innovation in the haemodynamic evaluation of portal hypertension. Azygos blood flow represents an index of blood flow through gastroesophageal collaterals and varices draining in the azygos vein. This technique has been very useful in the development of new forms of pharmacological therapy for portal hypertension.

Effects of vasopressin on the intravariceal pressure in patients with cirrhosis: comparison with the effects on portal pressure.

The present study investigated to what extent measurements of wedged and free hepatic venous pressures adequately reflect the effects of vasopressin at the esophageal varices in patients with cirrhosis. Eleven patients undergoing therapeutic sclerotherapy were studied by measuring wedged hepatic venous pressure, intravariceal pressure, free hepatic venous pressure, superior vena cava pressure and the intravascular pressure gradients wedged hepatic venous pressure-free hepatic venous pressure and intravariceal pressure-superior vena cava pressure, prior to and after vasopressin injection (1 IU, iv). Vasopressin caused a significant reduction in intravariceal pressure (from 22.5 +/- 9.4 to 19.2 +/- 8.4 mm Hg, p less than 0.001). Measurement of wedged hepatic venous pressure and free hepatic venous pressure closely reflected the reduction in variceal pressure. Thus, wedged hepatic venous pressure decreased by 16 +/- 11%, which is close to the 14 +/- 7% change in intravariceal pressure, and the 23 +/- 12% fall in the pressure gradient wedged hepatic venous pressure-free hepatic venous pressure was mirrored by the 26 +/- 10% change in intravariceal pressure-superior vena cava pressure. These pressure gradients decreased more than the absolute pressures (intravariceal pressure and wedged hepatic venous pressure) due to concomitant increases in superior vena cava pressure (1.9 +/- 1.9 mm Hg) and free hepatic venous pressure (0.6 +/- 1.9 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of somatostatin on splanchnic hemodynamics and plasma glucagon in portal hypertensive rats.

The effects of somatostatin infusion on splanchnic and systemic hemodynamics and plasma glucagon levels were investigated in rats with portal hypertension. Forty-four male Sprague-Dawley rats were studied. Portal hypertension was induced in 26 rats by partial portal vein ligation (PVL). These rats were divided in two experimental groups to receive blindly 1) somatostatin (PVL-SMT, n = 13) at a dose of 25 micrograms/kg body wt during 30 min preceded by a bolus injection of 15 micrograms/kg body wt or 2) placebo (saline) (PVL-P, n = 13) infused at the same rate as in the previous group. The remaining 18 rats were used as normal controls and received somatostatin (n = 9) or saline infusion (n = 9). Regional blood flows and cardiac output were measured using radioactive microspheres. Arterial and portal pressures were also measured. In portal hypertensive rats somatostatin infusion produced significant reductions in the increased portal venous inflow, reductions in portal pressure, and significantly increased portal venous resistance. Reduction of portal venous inflow was due to splanchnic vasoconstriction, evidenced by increased splanchnic arteriolar resistance. No significant differences were observed in systemic hemodynamic parameters between PVL-SMT and PVL-P rats. Plasma glucagon levels were significantly reduced by somatostatin to levels similar to those observed in sham-operated rats. In sham-operated rats, somatostatin also caused significant reduction in portal venous inflow and plasma glucagon concentration, although these changes were of lesser magnitude than in portal hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of somatostatin in patients with portal hypertension.

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.