肝硬化门脉高压患者入肝血流的超声评价

目的观测肝硬化门脉高压患者入肝血管(肝动脉、门静脉)血流动力学,探讨其与Child-Pugh肝功能分级、临床预后的关系.方法应用彩色多普勒超声分别检测35例正常健康人和37例肝硬化门脉高压患者的人肝血管的血流参数,分析肝硬化门脉高压入肝血管血流动力学参数与肝硬化分级关系.结果肝硬化门脉高压患者门静脉内径增宽,血流速度下降,充血指数增高,肝动脉血流阻力增高,与对照组有明显差异;肝硬化门脉高压患者Child-Pugh肝功能分级与门静脉内径无显著差异(P＞0.05),Child C级门静脉血流量显著减少,Child肝功能分级与门静脉的充血指数有关.结论测定入肝血管血流动力学参数有助于判断肝硬变门脉高压症的预后,为临床诊治提供依据.     

彩色多普勒超声对肝硬化门脉高压症患者肾血流动力学改变的研究

肝硬化门脉高压症患者随着病情加重，有效循环血量减少和肾内血管收缩，可造成肾小球滤过率下降，影响肾功能。晚期由于肾血管强烈收缩，肾小球滤过率极度下降，可形成肝肾综合征(HRS)，其死亡率很高，因此．早期发现和动态监测肝硬化门脉高压症患者的肾血流动力学改变，对于评估和监测肾血流灌注，预测HRS的发生具有参考价值。     

改良Sugiura手术治疗肝硬化门脉高压症并发上消化道出血的疗效

目的探讨改良Sugiura手术治疗肝硬化门脉高压症并发上消化道出血的临床疗效及安全性。方法将肝硬化门脉高压症并发上消化道出血72例患者按数字表法随机分为观察组和对照组各36例,观察组采用改良Sugiura手术,对照组采用传统的脾切除加贲门周围血管离断术,比较两组患者术后食管静脉曲张改善情况及术后并发症。结果观察组患者术后食管胃底静脉曲张改善情况明显优于对照组(P<0.05);肺部感染和肝性脑病等并发症发生率比对照组明显减少(P<0.05)。结论改良Sugiura手术是治疗肝硬化门脉高压症并发上消化道出血的较佳术式,具有断流彻底、安全性好、并发症少等优点,值得基层医院推广应用。     

大鼠肝硬化门脉高压症模型的研究

本实验在借鉴国内外复制肝硬化动物模型基础上,采用高浓度四氯化碳皮下注射及低浓度乙醇液口服的方法复制大鼠肝硬化门脉高压症。该模型稳定,肝硬化形成率高,至晚期均出现门脉高压,是研究肝硬化门脉高压症比较理想的动物模型。     

关于肝硬化门-体静脉分流术后肝衰竭的问题

门体静脉分流术曾一度是外科解决肝硬化门脉高压症的有效方法 ,在外科普遍流行。但随着对肝硬化门脉高压症病理机制认识的不断深入 ,以及对各种名称的门体静脉分流术临床效果的评价 ,其局限性逐渐显出。因此 ,有必要对这类手术在肝硬化门脉高压症中的应用情况进行重新评估。现通过分析我院近年来经颈静脉肝内门腔静脉支架分流术 ( TIPS术 )及外科限制性门腔静脉或脾肾静脉分流术后肝衰竭死亡病例 ,并结合国内外文献复习 ,就分流术的临床应用情况进行评估讨论。1　病例资料例 1 .女 ,2 5岁。主因腹胀、纳差、乏力半个月入院。根据病史、体…     

介入性门脉断流术对肝硬化门脉高压症患者血流动力学的影响

目的探讨介入性门脉断流术对肝硬化门脉高压症患者血流动力学的影响。方法随机选择2011年9月至2013年9月收治的肝硬化门脉高压症患者中54例,均实施介入性门脉断流术,观察患者术前、术后的血流动力学变化情况。结果经皮经肝胃食管曲张静脉栓塞术(PTVE)术后,较之术前,患者的门静脉压(FPP)出现显著上升的情况,差异有统计学意义(P0.05);联合性断流术后,较之术前,患者的FPP比较差异无统计学意义(P0.05)。术后患者的门静脉相关血流动力学未出现显著变化,但脾静脉血流速度和血流量较术前均显著降低,内径较之术前显著缩小,经比较差异均有统计学意义,(均P0.01,P0.05)。结论介入性门脉断流术对肝硬化门脉高压症患者血流动力学产生一定的影响。     

依那普利对门脉高压症患者血流动力学及肾素-血管紧张素-醛固酮系统的影响

门脉高压症是肝硬化的终末临床综合征,食管胃底静脉曲张破裂出血是其主要致死原因,病死率高达30%~60%。如何降低门脉高压,预防出血是大家关注的目标,但是目前尚无理想的治疗门脉高压症的药物。在门脉高压的形成、发展过程中肾素-血管紧张素-醛固酮系统起着不可忽视的作用。研究     

H2受体拮抗剂对门脉高压症门脉血液动力学影响的动物实验研究

目的探讨H2受体拮抗剂甲氰咪胍对肝硬化门脉高压症犬门脉血液动力学的影响。方法以胆总管结扎法成功制备胆汁性肝硬化门脉高压症模型犬11只,随机分为两组为甲氰咪胍组(n=7)、盐水对照组(n=4);另取4只正常犬为正常对照组。经股动脉、股静脉、右颈外静脉分别插管,以多导生理记录仪、电磁流量计等检测门脉及全身血液动力学变化,使用RF-3000型荧光分光光度计测量血浆组织胺浓度。结果甲氰咪胍组静脉注射甲氰咪胍5、15、306、0、90和120 min后,自由门脉压平均值均较注射前明显下降(Π<0.05),肝静脉楔入压、肝静脉压梯度、门静脉阻力均同步下降。肝动脉血流量无显著改变,门静脉血流量及全肝血流量轻度增多。肝静脉自由压、下腔静脉压、腹主动脉平均压及心率均无明显变化。自由门静脉压下降最大幅度与股静脉血血浆组织胺浓度呈显著正相关(p=0.7874,Π<0.05)。盐水对照组及正常对照组上述各指标均无显著变化。结论H2受体拮抗剂甲氰咪胍通过拮抗肝硬化门脉高压症犬血中异常升高的组织胺的作用,舒张肝血管床,降低门脉血流阻力,从而降低门脉压力,同时使门脉及全肝血流量轻度增加,而对全身血流动力学无不良影响。     

肝硬化病人门静脉高压症的多普勒超声研究

为了解肝硬化门脉高压病人门脉系统循环情况及为临床门脉高压的药物治疗提供客观依据，应用彩色多普勒超声检测２０例肝硬化病人及１５例正常人门脉系统血流动力学改变。结果：肝硬化门脉高压症病人门静脉、脾静脉、肠系膜上静脉的血管直径、血流速度、血流量均大于正常人（Ｐ＜０００５），而且发现门静脉血流量增加主要是脾静脉血流量增加所致．结论：肝硬化门脉高压病人存在门脉高动力循环状态，这对临床选择有效的治疗门脉高压症的方法有重要价值。     

多层螺旋CT静脉成像在肝硬化门脉高压症诊断中的应用

目的：探讨与分析多层螺旋CT静脉成像在肝硬化门脉高压症诊断中的应用价值。方法：选取2009年3月—2011年3月收治的通过病理或临床诊断为肝硬化早期以及中晚期的患者,对其进行多层螺旋CT静脉成像检查,对其门静脉与肝脏右静脉管径进行测量,并分析该检测方法对于肝硬化门脉高压症的诊断价值。结果：患者的血管显示均较为清晰,其门静脉宽度与正常人相比差异有统计学意义,而肝脏右静脉宽度在代偿期其内径有明显增宽的表现,失代偿期则有明显变窄的表现。本组患者的门静脉宽度/肝右静脉宽度（PV/RHV）值在失代偿期为（1.76±0.04）,与正常人相比差异有统计学意义。结论：采用多层螺旋CT对肝硬化门脉高压症有重要的诊断意义。     

Effects of endothelin in portal hypertensive rats.

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation. 2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats. 3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats. 4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature. 5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 +/- 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 +/- 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 +/- 0.53 fmol/ml). 6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.     

肝硬化门脉系统血流动力学与血浆内皮素关系的研究

【目的】探讨内皮素与门静脉系统血流动力学变化的关系。【方法】运用彩色多普勒超声观察32例肝硬化患者门脉系统血流动力学的变化,采用放免法对肝硬化患者外周血浆内皮素含量进行检测,分析门脉血流动力学指标与内皮素的相关性。【结果】肝硬化患者内皮素与门静脉脾静脉内径成正相关,与门静脉脾静脉血流量、血流速度不相关。【结论】内皮素在门脉高压的发生发展中起重要作用。     

In vitro vascular responsiveness to norepinephrine in experimental portal hypertension

It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease.     

Vascular smooth muscle cell signaling in cirrhosis and portal hypertension

Abnormal vascular responsiveness to ligands has been frequently observed in cirrhosis and portal hypertension, but its existence is not proven. The signaling pathways in vascular smooth muscle cells (VSMCs) have been studied only in animal models of cirrhosis and portal hypertension. Emerging evidence suggests that active relaxation, expressed as augmented content or activity of effectors within the cyclic AMP signaling pathway and suppressed content or activity of effectors in the inositol 1,4,5-trisphosphate/1,2-diacylglycerol signaling pathway, may be occurring in VSMCs of the splanchnic circulation in portal hypertension. The evidence supporting the existence of this phenomenon in the VSMCs of extrasplanchnic circulations in portal hypertension, as well as in the splanchnic circulation when chronic cellular damage is present, is very limited. The status of the other signaling pathways associated with contractile functions of the VSMCs, viz., cyclic GMP and tyrosine kinase-linked pathways, is unknown. The status of all the signaling pathways in non-contractile functions of VSMCs, such as growth and remodeling, has not been studied. As our overall understanding on the signaling pathways in VSMCs is only emerging, it is premature to implicate altered activity of the signaling pathways as the underlying basis of vascular hyporesponsiveness in cirrhosis and portal hypertension, and to extrapolate these limited observations to the human condition.     

The molecular mechanisms of cardiovascular and renal regulation by endothelin peptides.

In summary, we have seen that endothelins are potent cardiovascular and renal regulatory peptides. Cardiovascular regulation by endothelin requires complex spatial and temporal regulation of endothelin gene expression and the coordinated interplay of numerous signaling pathways. Although the precise physiologic role for endothelin peptides in the cardiovascular and renal systems remains uncertain, two general models can be proposed, as follows. (1) Endothelin appears to act as an autocrine or paracrine hormone involved in long-term (hours to days) regulation of cardiovascular and renal function in normal physiology. Similar regulation occurs in response to other cardiovascular hormones such as angiotensin II, atrial natriuretic peptides, and catecholamines. In this respect it is noteworthy that endothelin also interacts with other hormonal systems that affect cardiovascular status, such as renin-aldosterone and atrial natriuretic peptide (see references 9, 161, 162, and 213-217). (2) Endothelin might also function as a proinflammatory peptide, being locally produced at sites of vascular damage and injury. The fact that endothelin secretion is stimulated by cytokines, growth factors, and transforming growth factor beta is consistent with this role. In addition, the mitogenic actions of endothelin could contribute to vascular remodeling in the inflammatory response. A similar, defensive role has been proposed for other regulatory peptides. Endothelin has also been implicated in the pathogenesis of numerous disorders such as hypertension (see references 28, 56, 168, 184, and 224 through 226), cerebral and myocardial vasospasm (see references 180, 223, and 227 through 233), acute renal failure, and cyclosporine nephrotoxicity. It is clear that the development of specific ECE inhibitors and endothelin receptor antagonists will enable definitive experiments addressing the role of endothelin in normal physiology and the putative role of endothelin in the development of hypertension and other cardiovascular disorders. Further identification and biochemical analysis of signaling networks evoked by endothelin, in conjunction with physiologic studies, should provide a detailed understanding of the complex biologic events regulated by endothelin peptides.     

Use of ednit in the treatment of portal hypertension in patients with chronic hepatitis and liver cirrhosis]

AIM: To study ednit (ACE inhibitor) effectiveness in the treatment of portal hypertension in patients with chronic hepatitis (CH) and hepatic cirrhosis (HC). MATERIAL AND METHODS: The examination of 87 patients with active CH and 54 patients with HC at the preascytic stage included two-dimentional ultrasonic scanning of the abdominal organs with doppler fluometry of the vessels in the territory of the portal vein, tetrapolar rheohepatography, ultrasound investigation, angiography of the abdominal vessels. The patients received combined therapy with ednit in a dose 5 mg twice a day for at least 5 weeks. RESULTS: Patients with active CH and HC having portal hypertension treated with adjuvant ednit in the above dose achieved marked clinicobiochemical remission quicker, portal-hepatic circulation improved. CONCLUSION: The addition of ednit to therapy of active CH and HC with portal hypertension is effective as it lowers total peripheral vascular resistance which eventually results in a fall of pressure in the territory of the portal vein and improvement of hepatic circulation. The highest effect is reached in administration of 5 mg twice for 24 hours.     

An overview of pulmonary arterial hypertension: risks, pathogenesis, clinical manifestations, and management

This article focuses on pulmonary arterial hypertension, including both primary pulmonary hypertension (PPH) and those forms of pulmonary arterial hypertension that are related to other factors, including collagen vascular diseases, congenital shunts, portal hypertension, human immunodeficiency viral infection, and exposure to specific drugs and toxins. Risks for different types of pulmonary arterial hypertension are identified. The common pathogenesis for pulmonary arterial hypertension is discussed, and includes an overview of the role of key vasoactive substances such as nitric oxide, prostacyclin, endothelin, and thromboxane. Typical presenting clinical manifestations, recommendations for screening of patients at risk, and key diagnostic findings are discussed. The mainstay of treatment is identified as pharmacologic, and may include diuretics, digoxin, warfarin, calcium channel antagonists, and prostacyclin analogues such as epoprostenol. Surgical interventions are considered as a last resort, and may include unilateral or bilateral lung transplant or atrial septostomy. Treatment options for patients with pulmonary arterial hypertension hold more hope today than they did a decade ago and are identified so as to guide the advanced practice nurse in recognizing and then facilitating the appropriate management of patients with this rare but disabling disease.     

Effects of bosentan on cellular processes involved in pulmonary arterial hypertension: do they explain the long‐term benefit?

Pulmonary arterial hypertension is a rapidly progressing disease characterized by an over‐ expression of endothelin. In addition to its potent pulmonary vasoconstrictor effects, endothelin has been shown to produce many of the aberrant changes, such as hypertrophy, fibrosis, inflammation, and neurohormonal activation that underlie the shortened life span in pulmonary arterial hypertensive patients. The fact that endothelin expression correlates significantly with disease severity and outcome in these patients suggests that endothelin, through binding to both ET _A and ET _B receptor subtypes, is a key causative agent in the pathophysiology of pulmonary arterial hypertension. The orally active dual endothelin receptor antagonist bosentan ¹ competitively antagonizes the binding of endothelin to both endothelin receptor subtypes with high affinity and specificity. In animal models relevant for the pathophysiology of pulmonary hypertension, bosentan not only causes selective pulmonary vasodilation, but also prevents vascular hypertrophy and cardiac remodeling, attenuates pulmonary fibrosis, decreases vascular inflammation, and blunts neuro‐hormonal activation. These experimental data may explain the effects on disease progression and the long‐term benefit observed with bosentan in pulmonary arterial hypertension.     

Successful treatment of portopulmonary hypertension with the selective endothelin receptor antagonist Sitaxentan

Portopulmonary hypertension (POPH) is a rare complication of portal hypertension. Prostanoids have been shown to be effective in the treatment of POPH and have been used as a bridge to liver transplantation. More recently, case series revealed beneficial effects of both the dual endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil. The efficacy of sitaxentan, a selective endothelin receptor A (ERA) antagonist in the reversal of POPH, is still unclear. We report a case of POPH that was successfully treated with oral sitaxentan. Haemodynamic and symptomatic improvements were maintained after a 12-week long-term treatment period. Additionally, hepatic vein pressure gradient significantly decreased from 12 mmHg to 8 mm after treatment with sitaxentan. This is the first reported case of a successful therapy with a selective ERA antagonist in a patient suffering from POPH. Oral sitaxentan therapy might be a promising new option for patients suffering from POPH.     

Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension

The accuracy of various Doppler parameters of portal circulation in the diagnosis of relevant portal hypertension (presence of gastroesophageal varices) was prospectively validated. The following parameters were compared in 51 patients with chronic liver disease (40 with cirrhosis and 11 with chronic hepatitis): portal vein flow velocity and congestion index, hepatic and splenic arteries resistance indexes (RI), modified liver vascular index (portal flow velocity/hepatic artery RI) and portal hypertension index, a new index calculated as: [(hepatic artery RI x 0.69) x (splenic artery RI x 0.87)]/portal vein flow velocity. Highest accuracy was achieved by the splenic artery RI and the portal hypertension index (both around 75%) at cut-offs, respectively, of 0.60 and 12 cm/s(-1), which appeared to be, therefore, the most favorable parameters for the clinical practice. Their use may limit the need for endoscopy to search for varices.