Effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension

The effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis is not clearly defined, as some authors report a decrease in portal pressure and in liver blood flow during intravenous administration of this hormone, while others do not. In 19 subjects with liver cirrhosis and portal hypertension the following parameters were measured before and during intravenous administration of somatostatin (7.5 micrograms/min): porto-hepatic gradient, estimated hepatic blood flow, specific splenic blood flow, cardiac index. Estimated hepatic blood flow decreased significantly during somatostatin infusion (p less than 0.05), averaging a 13% decrease; porto-hepatic gradient, splenic specific blood flow and cardiac index did not vary significantly. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min induces a slight decrease in liver blood flow without affecting portal hypertension.     

Influence of the degree of liver failure on portal blood flow in patients with liver cirrhosis

Portal vein haemodynamics as demonstrated by the pulsed Doppler system were studied in 37 patients with cirrhosis who had been classified in three groups (A, B, and C) in accordance with the degree of liver failure. Maximal inner diameter of the portal vein was significantly lower in patients who were considered to be in good condition (group A) than in patients with moderate and severe liver failure (group B and group C) (p less than 0.001). A significant difference was also found between group A and group B and between group A and group C with regard to the portal blood velocity and portal blood flow (p less than 0.001). In accordance with the presence and size of the oesophageal varices, in patients with large varices the portal blood velocity and portal blood flow were significantly lower than in patients without varices (p less than 0.001), whereas maximal inner portal vein diameter was significantly higher (p less than 0.001). This study demonstrated that in patients with cirrhosis circulatory alterations in the portal vascular bed may be, at least in part, an indicator of the stage of liver disease.     

Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis

The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05-0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of metoclopramide on portal blood flow in patients with liver cirrhosis, measured by the pulsed Doppler system

The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemodynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemodynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 +/- 1.1 to 10.8 +/- 1.2 cm/sec and from 769.0 +/- 87.7 to 707.9 +/- 84.2 ml/min, respectively (p less than 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p greater than 0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension.     

Effect of somatostatin versus octreotide on portal haemodynamics in patients with cirrhosis and portal hypertension

OBJECTIVES: Elevated portal inflow is part of the pathogenesis of portal hypertension in patients with cirrhosis. Vasoactive substances appear to play a primary role in the regulation of portal flow. The aim of this study was to investigate the effects of somatostatin and octreotide on portal pressure and plasma levels of insulin-like growth factor (IGF-1), nitric oxide (NO), endothelin-1 (ET-1) and glucagon (GLU). METHODS: Portal pressures of 14 cirrhotic patients with portal hypertension who underwent transjugular intrahepatic portosystemic shunt (TIPS) were directly measured via a catheter placed in the portal vein. Portal pressure and IGF-1, NO, ET-1 and GLU plasma levels were determined at baseline, and at 8 h and 24 h after administration of somatostatin or octreotide via portal vein catheter in a randomized, double-blind, cross-over design. RESULTS: The average decrease in portal pressure after intravenous infusion of somatostatin and octreotide was 9.4 +/- 1.0 cmH2O and 5.0 +/- 1.0 cmH2O, respectively (P < 0.01). Plasma levels of GLU and IGF-1 decreased significantly 8 and 24 h after somatostatin and octreotide infusion (P < 0.05). However, there were no significant decreases in plasma NO or ET-1 levels. There was a significant difference between somatostatin and octreotide groups (P < 0.01). CONCLUSION: Both somatostatin and octreotide can significantly reduce portal pressure, although somatostatin is more potent than octreotide. The underlying mechanisms may involve inhibition of the secretion of GLU, IGF-1 and other hormones as well as a decrease in hepatic metabolism and portal inflow leading to a reduction in portal pressure.     

H2受体阻滞剂联合多潘立酮对肝硬化患者门脉血流的影响

目的:探讨H2受体阻滞剂联合多潘立酮对肝硬化患者门静脉系统血流量的影响.方法:以20名健康人作为正常对照,60例肝硬化患者随机分成3组,分别给予口服高舒达、口服多潘立酮以及联合用药,治疗前后采用多普勒超声测定门静脉(PVF)、脾静脉(SVF)和肠系膜上静脉(SMVF)血流量(mL/min).结果:治疗后,H2受体阻滞剂组的PVF显著高于治疗前(850.23±140.78 vs 695.22±221.44,P＜0.01),SVF和SMVF低于治疗前,但无显著差异.多潘立酮组PVF较治疗前有增高,无显著差异,而SVF和SMVF显著低于治疗前(SVF:598.13±272.33 vs 816.40±279.61,P＜0.05;SMVF:504.23±1 88.54 vs 640.30±200.12,P＜0.05).联合用药组则PVF显著高于治疗前(876.76±178.65 vs 70534±200.15,P＜0.05),而SVF、SMVF显著低于治疗前(SVF:605.33±252.86 vs 798.33±280.45,P＜0.01;SMVF:503.43±175.25 vs 650.19±190.62,P＜0.01).结论:H2受体阻滞剂组及多潘立酮都具有改善门静脉系统血流的作用,联合应用作用更为明显.     

The effects of selective and non-selective adrenoceptor blockade on the portal blood flow in patients with liver cirrhosis

The effects of different types of adrenoceptor blocking agents on portal venous blood flow were studied in 10 patients with liver cirrhosis by using a duplex Doppler system. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta blocker), and labetalol (non-selective adrenoceptor blocker) were compared. The drugs were administered at random at an interval of 3 days or more. Hemodynamic measurements were done before and after 1 h, 2 h, and 3 h of therapy. Atenolol and propranolol produced significant decrease in the portal vein cross-sectional area, portal blood velocity, and estimated volume of the portal blood flow. The portal blood velocity decreased by 13.1 +/- 7.2% 3 h after atenolol and by 16.2 +/- 6.5% 3 h after propranolol administration (p less than 0.05). Labetalol had no significant influence on portal venous hemodynamics. These results support the hypothesis that a decrease in portal venous flow induced by beta blockers is at least partly mediated with alpha-adrenergic receptors.     

Noninvasive measurement of portal venous blood flow in patients with cirrhosis

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038±539 to 1572±759 ml/min,P<0.02); this effect was due to a significant rise in mean blood velocity (from 18.5±3.7 to 23.9±3.9 cm/sec,P<0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985±491 to 625±355 ml/min,P<0.05); a significant decline of mean blood velocity (from 18.8 ±4.5 to 14.5±2.5 cm/sec,P<0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.     

Effect of hepatic collateral hemodynamics on gastric mucosal blood flow in patients with liver cirrhosis

The dependence of the gastric mucosal change in liver cirrhosis on the extrahepatic collaterals is still unknown. Therefore we studied the influence of these collateral hemodynamics on gastric mucosal blood flow and gastric mucosal lesions. The subjects were 23 cirrhotic patients and were divided into two groups by the findings of percutaneous transhepatic portography. The first group consisted of 14 cases whose extrahepatic collaterals were via esophageal varices (group I). The second group included 9 cases having collaterals other than esophageal varices (group II). Multiple red spots were observed in 13 of 14 cases in group I, and two of nine cases in group II. Gastric mucosal blood flow was 2.0±0.9 volts (mean±sd) in group I, 4.0±1.2 in group II. A statistically significant difference was observed between groups I and II. Gastric mucosal blood flow was not significantly correlated with portal venous pressure in group I. It is concluded that, in liver cirrhosis, gastric mucosal blood flow is changeable according to the types of the extrahepatic collaterals.     

Effects of terlipressin and somatostatin on liver and thorax blood volumes in patients with cirrhosis

Background: Variceal bleeding in cirrhosis can cause liver ischaemia and deteriorate the hyperdynamic state; thus, the effects of vasoconstrictor therapy on liver blood volume (LBV) and thorax blood volume (ThBV) are important. Aim: To evaluate and compare the effects of terlipressin and somatostatin on LBV and ThBV in stable patients with cirrhosis and portal hypertension. Methods: Twenty patients were studied (Child–Pugh class A/B/C: 5/8/7). The radioactivities in the liver region (LRR) and the thorax region (ThRR) by single‐head gamma camera technique, as indicators of LBV and ThBV, respectively, and systemic haemodynamics were measured at baseline and after intravenous infusion of 2 mg of terlipressin (n=10) or somatostatin 250 mg/h after an initial bolus of 250 mg (n=10). Results: LRR and ThRR decreased significantly with increasing severity of cirrhosis. Thirty minutes after terlipressin infusion, LRR and ThRR increased by 7.8 ± 4.4% (NS) and 14 ± 5.3% (P=0.01) compared with baseline values; the increase in ThRR was significantly related to the increase in LRR (r=0.682, P=0.03). In contrast, somatostatin reduced LRR and ThRR by 13.3 ± 6.5% (P=0.07) and 1 ± 4% (NS) respectively. LRR and ThRR increased significantly in the terlipressin group compared with the somatostatin group (P=0.01 and P=0.02 respectively). Terlipressin reduced cardiac output and heart rate (both P=0.01) and increased the mean arterial pressure (MAP) and systemic vascular resistance (P=0.009 and P=0.002 respectively); MAP decreased after somatostatin infusion (P=0.03). Conclusions: Terlipressin, but not somatostatin, maintains LBV, increases ThBV and improves the hyperdynamic state in cirrhosis. These effects can be beneficial in variceal bleeding, particularly in patients with advanced liver disease.     

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.     

Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients.

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.     

Effect of somatostatin on splanchnic hemodynamics in patients with cirrhosis of the liver and in normal subjects

The effect of somatostatin on splanchnic hemodynamics was determined in 8 patients with cirrhosis of the liver and in 18 normal subjects using arterial-hepatic-venous catheterization. Estimated hepatic blood flow determined by indocyanine green infusion was 1.36 +/- 0.23 L/min (+/- SEM) in patients with cirrhosis and remained unaffected during 30 min of somatostatin (250 microgram/h) administration. Wedged hepatic venous pressure which was elevated to 23 +/- 1.8 mmHg was also uninfluenced. In contrast to somatostatin, an infusion of vasopressin (12 U/h for 30 min) given to the same patients, lowered estimated blood flow by 28% (p < 0.05) and wedged hepatic venous pressure by 18% (p < 0.02). Arterial gastrin and insulin levels were lowered during somatostatin infusion by 33% (p < 0.02) and by 75% (p < 0.005), respectively. In contrast to the cirrhosis, infusion of 250 microgram/h somatostatin into normal subjects was associated with a decrease of estimated hepatic blood flow from 1.20 +/- 0.16 to 0.88 +/- 0.12 L/min (p < 0.01) representing a 27% decline. Arterial gastrin and insulin concentrations were lower (p < 0.01) than in cirrhosis, but the basal levels were lowered by somatostatin to a similar degree in both groups of patients. A higher dose of somatostatin (500 microgram/h) administered to normal subjects resulted in a similar decrease of gastrin and of estimated hepatic blood flow as that seen with 250 microgram/h, whereas a lower dose (125 microgram/h) decreased gastrin but failed to influence estimated hepatic blood flow. Thus, somatostatin at a dose which has been used in the treatment of acute peptic ulcer hemorrhage (250 microgram/h) failed to influence estimated hepatic blood flow and wegded hepatic venous pressure in patients with cirrhosis but lowered splanchnic blood flow in normal subjects. Assuming that this effect contributes to somatostatin's therapeutic efficacy, these results cast doubt on its potential value in the treatment of upper gastrointestinal bleeding of cirrhotics with portal hypertension.     

普萘洛尔与5-单硝酸异山梨醇酯联用对肝硬化门静脉血流动力学的影响

通过彩色多普勒超声显像仪观测普萘洛尔与5-单硝酸异山梨醇酯(ISMN)联用对肝硬化门静脉血流动力学的影响。19例乙型肝炎后肝硬化患者并有内镜证实的食管静脉曲张。治疗组ISMN 20mg,每日2次,普萘洛尔10mg～20mg,每日3次;对照组为健康受试者。采用同个体自身治疗前后对照研究。结果表明应用普萘洛尔与ISMN治疗1周后,Dpv、Vpv均显著性下降(P<0.01),Opv也显著性降低(711.76±515.52 vs 484.02±222.93)mL/min,P<0.01;Qsv显著性降低(558.07±354.62 vs 394.02±267.57)ml/min,P<0.01;但Qsmv的变化不明显(P>0.05)。治疗4周后也获得了同样的效果。普萘洛尔与ISMN联用可以降低Qpv和Qsv,具有预防上消化道出血的作用。     

Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.     

Spontaneous intermittent reversal of blood flow in intrahepatic portal vein branches in cirrhosis of the liver

The intrahepatic portal venous flow in cirrhosis of the liver was evaluated by percutaneous transhepatic portography and hepatic arteriography. Spontaneous reversal of flow in segmental portal vein branches was documented. Changes in hepatic arterial inflow and portal venous pressure may result in intermittent changes in the direction of flow in segmental portal venous branches within the cirrhotic liver. Segmental reversal of blood flow seems to be the precursor of total hepatofugal portal flow.     

Surgical treatment of portal hypertension in patients with liver cirrhosis

Surgical options in the treatment of portal hypertension in cirrhotics are reviewed, regarding elective and emergency cases as well as the results in alcoholics and non-alcoholics. After literature review and personal experience analysis, it is concluded that endoscopic sclerotherapy should be the treatment of choice in cirrhotic patients with bleeding esophageal varices. When this fails, distal splenorenal shunt is indicated for compensated Child A and B. Regarding Child C and decompensated Child B, the choice should be a portocaval or meso caval shunts or esophageal transection with a stapler associated to splenectomy.     

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.