丹参等活血化淤中药对门脉高压血流动力学影响的临床与实验研究

目的探讨丹参、当归等及硝苯啶对门脉高压血流动力学的影响。方法采用血管插管测定胆管结扎肝硬化犬门脉系统压力变化；超声多普勒观测肝硬化患者门脉血流动力学变化。结果（１）静脉滴注丹参、当归后，肝硬化犬门静脉压（Ｐｐｖ）、嵌塞肝静脉压（ＷＨＶＰ）、肝静脉压力梯度（ＨＶＰＧ）显著降低（Ｐ＜０．０５～０．０１），平均动脉压（ＭＡＰ）、心率（ＨＲ）无明显变化（Ｐ＞０．０５），硝苯啶则使Ｐｐｖ，ＷＨＶＰ，ＭＡＰ．ＨＲ显著降低（Ｐ＜０．０５）。（２）丹参、丹参＋硝苯啶．丹参＋水＋硝苯啶口服药１０－１２周，能显著降低肝硬化患者门静脉内径（Ｄｐｖ）、脾静脉内径（Ｄｓｖ）．门静脉血流量（Ｑｐｖ），脾静脉血流量（Ｑｓｖ）（Ｐ＜０．０５－０．０１，当归作用较弱。结论对比表明，丹参、当归等中药较硝苯啶对门脉压力作用为慢，但较持久，无副反应。     

Clinical and experimental study of effect of Raondix Salviae Militiorrhiza and other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension

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Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.     

Effects of vasopressin on left gastric venous flow in cirrhotic patients with esophageal varices

To assess vasopressin control of esophageal variceal bleeding, we investigated the effect of vasopressin on the left gastric venous flow, portal venous flow, superior mesenteric venous flow, and splenic venous flow in seven cirrhotic patients with esophageal varices, using a duplex system consisting of a real-time ultrasonograph and an echo-Doppler flowmeter. Infusion of vasopressin (0.3 U/min) significantly decreased the blood flow in the left gastric vein (-56%), portal trunk (-54%), superior mesenteric vein (-54%), and splenic vein (-56%) as a result of decrease of blood velocity in these vessels. Thus, vasopressin seems to control esophageal variceal bleeding, in part, by reducing blood velocity and blood flow in the left gastric vein following reduction of blood velocity and blood flow in the superior mesenteric vein and splenic vein.     

多普勒彩超评估甲氧乙心安联合硝酸异山梨醇酯治疗门静脉高压的效果

目的：评估甲氧乙心安（商品名：倍他乐克）联合硝酸异山梨醇酯（商品名：消心痛）预防肝硬化患者上消化道出血和再出血的效果与安全性。方法：应用多普勒彩超检测２２例肝硬化门静脉高压患者经倍他乐克联合消心痛治疗前后门静脉系统血流动力学变化，并观察治疗前后血压、心率及肝功能变化。结果：治疗前门静脉主干、脾静脉及肠系膜上静脉平均内径较正常组明显增宽，平均血流速度明显减慢，平均血流量明显增多。治疗后三者平均内径无明显变化（Ｐ＞０．０５），但与治疗前比较，平均流速明显减慢，平均血流量明显减少（Ｐ＜０．０５）。结论：倍他乐克联合消心痛降门静脉压治疗安全有效。多普勒彩超对门静脉高压的诊断和治疗评估有重要意义。     

Effect and mechanism of action of isosorbide-5-mononitrate.

Nitrates have been shown to decrease portal pressure in cirrhotic patients with portal hypertension and this has been attributed to decreased portal venous resistance. We studied the effect and mechanism of action of oral administration of isosorbide-5-mononitrate (Is-5-Mn) (20 mg), which, unlike the dinitrate, does not require hepatic biotransformation to a vasoactive metabolite on portal and systemic haemodynamics in 11 patients with portal hypertension complicating cirrhosis. A significant reduction in portal pressure gradient (WHVP-FHVP) (from 23.9 (3.4) to 21.8 (3.4) mmHg: p less than 0.005) occurred 60 minutes after Is-5-Mn due entirely to a fall in WHVP, associated with decreased estimated liver blood flow (from 1940 (159) to 1639 (179) ml/min: p less than 0.05). Right atrial and pulmonary artery pressures and cardiac index fell significantly whilst mean arterial pressure remained unaffected. Heart rate and the calculated systemic vascular resistance index increased significantly. Significant correlations existed between the reduction in portal pressure gradient and fall in cardiac index (r = 0.65, p less than 0.05) and increase in systemic vascular resistance index (r = 0.72, p less than 0.02). The observed decrease in estimated liver blood flow, in association with an increase in systemic vascular resistance index, suggests that baroreceptor mediated splanchnic vasoconstriction may be one of the factors responsible for the fall in portal pressure, rather than portal venous dilatation.     

Combined liver vein and spleen pulp pressure measurements in patients with portal or splenic vein thrombosis

BACKGROUND: Patients with thrombosis of the portal or splenic vein may develop portal hypertension with bleeding from oesophageal or gastric varices. The relevant portal pressure cannot be measured by liver vein catheterization or transhepatic puncture of the portal vein because the obstruction is peripheral to the accessible part of the portal system. METHODS: Liver vein catheterization was combined with percutaneous splenic pressure measurement in 10 patients with portal or splenic vein thrombosis and no cirrhosis, and 10 cirrhotic patients without thrombosis. The splenic pressure was measured by percutaneous puncture below the curvature of the ribs with an angle of the needle to skin of 30 degrees in order to minimize the risk of cutting the spleen if the patient took a deep breath. RESULTS: None of the patients in whom the described procedure was followed had complications. Pressure measurements in the spleen pulp and splenic vein were concordant. The pressure gradient across the portal venous system (splenic-to-wedged hepatic vein pressure) was -1.3 to 8.5 mmHg (median, 2.8 mmHg) in cirrhosis patients and 0-44 mmHg (median, 18 mmHg) in thrombosis patients, the variation reflecting various degrees of obstruction to flow in the portal venous system. Peripheral portal pressure (splenic-to-free liver vein pressure gradient) was 1.1-28 mmHg (median, 17 mmHg) in cirrhotic patients and 11-52 mmHg (median, 23 mmHg) in thrombosis patients. CONCLUSIONS: Liver vein catheterization combined with percutaneous splenic pressure measurement is feasible in quantifying pressure gradient across a thrombosis of the portal/splenic vein and in quantifying portal pressure peripheral to this kind of thrombosis.     

Partial splenic embolization in patients with liver cirrhosis and hepatocellular carcinoma: Effects on portal hemodynamics

Partial splenic embolization (PSE) was performed on patients with liver cirrhosis to control hypersplenism and gastroesophageal varices. In this study, we evaluated the effects of PSE on the portal hemodynamics and hepatic function of 17 cirrhotic patients with hepatocellular carcinoma. The mean splenic volume and the peak platelet count increased significantly and the splenic vein pressure decreased significantly after PSE. However, the portal blood flow did not change. Changes in the 15-min retention rate of indocyanine green and the arterial ketone body ratio were not significant, but the redox tolerance index increased from 0.24 ± 0.28 × 10^?2 to 0.59 ± 0.35 × 10^?2. These results suggest that PSE may reduce perioperative risks in cirrhotic patients with hepatocellular carcinoma who are candidates for hepatic resection.     

肝硬化患者血浆内皮素和胰高血糖素水平的变化及其临床意义

目的 研究肝硬化时血浆内皮素-1(ET-1)和胰高血糖素(GLU)水平的改变及其与肝功能损害和门脉高压形成的关系。方法 采用放射免疫分析法测定40例肝硬化患者和18例对照组空腹血浆ET-1和GLU水平。用彩色多普勒超声测定门静脉及脾静脉的直径、流速和流量。结果 肝硬化患者血浆ET-1和GLU水平显著高于对照组。按肝功能Child-Pugh分级将肝硬化患者分为A、B、C三组，各组血浆ET-1和GLU水平依次升高。合并腹水的肝硬化患者血浆ET-1和GLU水平显著高于未合并腹水者。血浆ET-1和GLU水平与门静脉和脾静脉的直径以及脾静脉的流量呈显著正相关。结论 肝硬化患者血浆ET-1及GIU水平升高反映了肝功能损害的严重程度，同时在门静脉高压的形成和发展过程中起着重要的作用。     

Portal hypertension: Serotonin and pathogenesis

Summary It has been demonstrated that serotonin (5-hydroxytryptamine; 5HT) can decrease portal vascular resistance in animals and could be a possible mediator for intestinal vasodilation. Moreover, isolated mesenteric vein from portal hypertensive rats has been shown to be hyper-responsive to 5HT. Hence 5HT may play a role in the pathophysiology of the hyperkinetic syndrome observed in patients with portal hypertension. This hypothesis that serotonin might increase splanchnic blood flow, and hence portal pressure, led us to propose that 5HT receptor antagonists might decrease portal hypertension. We observed that acute administration of ketanserin, an antagonist of serotonin at 5HT₂ receptors, significantly decreased portal pressure and portal-systemic collateral blood flow in patients with cirrhosis, whereas hepatic blood flow was not modified. Arterial pressure slightly decreased, while cardiac output was not affected by ketanserin. These findings were also observed during continuous administration of ketanserin. More recently, it has been shown that ritanserin, a more specific 5HT₂ receptor antagonist, significantly decreased portal pressure in cirrhotic patients. Finally, in rats with portal hypertension, ketanserin as well as ritanserin produced significant reductions in portal pressure but did not modify portal tributory blood flow. In these portal hypertensive animals, 5HT₂ antagonists may act on hepatocollateral vascular resistance. These studies confirm current evidence in favor of a role for the actions of serotonin via 5HT₂ receptors in portal hypertension and add a new group of substances for its treatment.     

肝硬化患者肝功能失代偿状况与门脉管径的关系

目的:探讨肝硬化患者肝功能失代偿状况、食管静脉曲张程度与门脉主干内径及脾静脉内径的关系。方法:对100例肝硬化失代偿期患者进行肝功能Child-pugh分级,内镜检查判断食管静脉曲张程度,彩色多谱勒B超检测门静脉主干内径及脾静脉内径。结果:肝功能分级越差,门静脉与脾静脉的内径越大(P<0.05),且随着门静脉及脾静脉内径增大,食管静脉曲张程度亦加重(P<0.05)。结论:门静脉及脾静脉内径能间接体现门静脉高压的程度,继而反映肝功能失代偿状况。     

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.     

Portal hemodynamics in idiopathic portal hypertension (Banti's syndrome). Comparison with chronic persistent hepatitis and normal subjects

A comparative study of portal hemodynamics was made in 17 patients with idiopathic portal hypertension, 5 patients with chronic persistent hepatitis having no portal hypertension, and 21 healthy adults who served as the control for certain measurements. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, organ volume by computed tomography, and intrahepatic shunt index by 99mTc-macroaggregated albumin instilled in the portal vein. The patients with idiopathic portal hypertension were divided into two groups: group A (n = 8) and group B (n = 9), consisting of those who respectively had portal venous flow per liver volume above and below the mean + 2 SD of healthy adults. In group A, portal vein pressure was moderately elevated, portal venous flow was significantly increased compared with the control, and portal vascular resistance was not much altered. In group B, portal vein pressure was markedly elevated above that of control, portal venous flow was comparable, and portal vascular resistance was significantly elevated. Splenic venous flow measured in the splenic vein between the left and short gastric veins was markedly increased in groups A and B, the increase being greater in the former. It was concluded that in some patients with idiopathic portal hypertension, increased portal venous flow, partly a result of increased splenic venous flow secondary to splenomegaly of an undetermined process, is the main contributor initially to the elevation of portal vein pressure; in others, possibly later, increased portal vascular resistance plays an important role.     

Mechanisms of a clonidine-induced decrease in portal pressure in normal and cirrhotic conscious rats

The effects of clonidine on portal pressure and splanchnic blood flow were studied in conscious rats with sinusoidal portal hypertension due to cirrhosis induced by bile duct ligation. In cirrhotic and sham-operated rats, clonidine (20 micrograms per kg body weight, intravenously) significantly reduced portal, pressure from 19.0 +/- 0.6 to 14.5 +/- 1.0 mmHg and from 9.8 +/- 0.9 to 7.3 +/- 0.5 mmHg, respectively. No significant change in systemic hemodynamics was observed. In cirrhotic rats, clonidine reduced portal pressure, probably by producing a significant increase in portal tributary vascular resistance leading to a 25% decrease in portal tributary blood flow (radioactive microsphere method). In sham-operated rats, clonidine reduced portal pressure presumably by decreasing hepatic portal vascular resistance, since no significant change in portal tributary blood flow was observed. In both groups, clonidine administration significantly decreased plasma noradrenaline concentration. Placebo administration produced neither significant hemodynamic nor significant plasma noradrenaline concentration change. These findings indicate that the sympathetic regulation of the splanchnic circulation is impaired in cirrhotic rats.     

非洛地平缓释片与心得安联用对肝硬化患者门脉血流动力学的影响

目的探讨非洛地平缓释片和心得安联合应用对肝硬化门脉高压的治疗作用.方法69例肝硬化门脉高压患者随机分为非洛地平组、心得安组和联合用药组,以多普勒超声检测三组患者治疗前、后门脉血流动力学的变化.结果治疗4周后,联用组门脉流速、流量及脾静脉内径、流速、流量均较治疗前有明显减少.门脉流速、流量、脾静脉血流量的减少联用组较其他两组明显(P＜0.05),此外脾静脉内径、血流速度联用组还较心得安组明显减少(P＜0.05).三组患者治疗后平均动脉压无显著下降.结论非洛地平缓释片和心得安联合应用较单一应用具有更好的降低肝硬化患者门脉压力的作用.     

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.     

Mixed endothelin receptor antagonist, SB209670, decreases portal pressure in biliary cirrhotic rats in vivo by reducing portal venous system resistance

BACKGROUND/AIMS: This study aimed to evaluate the hemodynamic effects of endothelin-1 or mixed endothelin receptor antagonist, SB209670 in cirrhotic rats, and to elucidate the role of endothelin in cirrhotic portal hypertension. METHODS: Secondary biliary cirrhosis was induced by bile duct ligation. Hemodynamics were studied using the radioactive microsphere technique. RESULTS: Plasma and hepatic endothelin levels in cirrhotic rats were significantly higher than those in normal rats (plasma, 9.0+/-1.3 vs. 2.6+/-0.5 pg/ml, p<0.001; liver, 74.8+/-13.3 vs. 12.6+/-2.5 pg/g wet tissue, p<0.001). Intraportal administration of endothelin-1 (3 nmol/kg) progressively raised portal pressure without an initial transient reduction, which was observed in systemic arterial pressure, in both cirrhotic and normal rats. SB209670 (5.4 micromol/kg) reduced portal pressure in cirrhotic rats (-19+/-5%, p<0.01) without modifying systemic arterial pressure and renal blood flow, but not in normal rats. This reduction was associated with reduced portal venous system resistance (vehicle, 2.5+/-0.2 vs. SB209670, 1.7+/-0.1 mmHg x min x 100 g bw/ml, p<0.01), but not with change in portal venous inflow and collateral blood flow. CONCLUSIONS: Mixed endothelin antagonist, SB209670, decreased portal pressure by reducing portal venous system resistance without modifying systemic arterial pressure and renal blood flow in cirrhotic rats. This result, together with the findings that plasma and hepatic endothelin levels were elevated in cirrhotic rats and that exogenous endothelin-1 increased portal pressure, provides further support for a role of endothelin in portal hypertension and suggests a potential use of mixed endothelin antagonist in the pharmacological treatment of portal hypertension.     

Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease.

PURPOSE: To evaluate the correlation between hepatic vein pressure gradient measurement and Doppler ultrasonography (DUS) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: Sixty-six patients with fibrotic to cirrhotic hepatitis C virus-related CLD, were consecutively included upon referral to our haemodynamic laboratory. Superior mesenteric artery pulsatility index (SMA-PI), right interlobar renal and intraparenchymal splenic artery resistance indices, were determined, followed by hepatic venous pressure gradient (HVPG) measurement. RESULTS: A correlation was found between HVPG and intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, P<0.0001), SMA-PI (r=-0,48, P<0.0001), right interlobar renal artery resistance index (RRA-RI) (r=0.51, P<0.0001) in the whole patient population. However, dividing patients according to the presence/absence of severe portal hypertension (i.e. HVPG > or =12 mmHg), a correlation between HVPG and intraparenchymal SA-RI (r=0.70, P<0.0001), SMA-PI (r=-0.49, P=0.02), RRA-RI (r=0.66, P=0.0002) was observed only for HVPG values <12 mmHg. HVPG but not DUS correlated with the presence of esophageal varices (P<0.0001). CONCLUSIONS: Superior mesenteric artery pulsatility index, intraparenchymal splenic and right interlobar renal artery resistance indices do not adequately predict severe portal hypertension.     

肝积合剂对肝硬化门静脉高压的影响

目的：探讨肝积合剂对肝硬化门脉高压的影响。方法：将60例肝硬化门脉高压症患者随机分为两组，治疗组患者口服中药肝积合剂，对照组患者口服心得安，共3个月。用彩色双功能多普勒超声诊断仪测量门静脉内径、脾静脉内径、门静脉血流速度、脾静脉血流速度。采用胃镜观察食管静脉曲张部位、条数、形态、颜色及胃底有无静脉曲张。结果：肝积合剂可显著缩小肝硬化患者门静脉及脾静脉内径、加快血流速度、减少血流量。尤其在加快门静脉、脾静脉血流速度及减少血流量上与心得安比较，差异有显著性意义（P〈0．05）。结论：肝积合剂对肝硬化门脉高压症有一定的防治作用。     

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 haemortynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemo-dynamics 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 < 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p >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.