Stretch-dependent modulation of contractility and growth in smooth muscle of rat portal vein

Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy and altered contractility in 1 to 7 days. We have used organ cultures to investigate mechanisms involved in this adaptation to mechanical load. Strips of rat portal vein were cultured for 3 days, either undistended or loaded by a weight. Length-force relations were shifted toward longer length in stretched cultured veins compared with freshly dissected veins, whereas the length-force relations of unstretched cultured veins were shifted in the opposite direction. This occurred after culture either with or without 10% FCS to promote growth. The wet weight of loaded veins increased by 56% in the presence of FCS, whereas that of undistended control veins increased by 24%. No weight increase was seen in serum-free culture. The dry/wet weight ratio decreased during culture with FCS but was not affected by stretch. Electron microscopy revealed increased cell cross-sectional area in stretched relative to unstretched veins, and protein contents were greater, as were [(3)H]thymidine and [(3)H]leucine incorporation rates. Growth responses were associated with the activation of stretch-sensitive extracellular signal-regulated kinases 1 and 2 and were inhibited by herbimycin A and PD 98059, inhibitors of extracellular signal-regulated kinases 1 and 2. The results demonstrate that by culture of whole vascular tissue, smooth muscle cells are maintained in the contractile phenotype and respond to stretch with a physiological adaptation involving hypertrophy/hyperplasia and remodeling of the contractile system, similar to that in vivo. Mechanical stimulation and growth factors are both required for functionally significant growth.     

肠系膜上静脉胰后干和门静脉干测量的临床意义

目的为提高近端胆管癌和壶腹周围癌的手术切除率，使该区域受肿瘤浸润的血管能一并与肿瘤器官同时切除，并使血管直接重建．方法在实施肝门胆管癌切除术及胰十二指肠切除术中，对肝蒂内门静脉干（portalveintrunk，PV）、胰腺钩突内的肠系膜上静脉子即“胰后干”（post－pancreastrunk，PPT）进行解剖学定位并进行分段测量长度及可以纵向折叠的长度，以此估计可切除的静脉长度及重新再建血管的长度结果测量肝蒂内门静脉干104例，长度男5．8cm±2．0cm，女5．5cm±0．8cm.优势长度大于4.5cm，男56例，占76．7％；女25例，占80．6％胰腺钩突内段肠系膜上静脉子测量54例长度，男3．7cm±0．8cm，女3．5cm±0．6cm；优势长度大于3．0cm者,男28例，占77．6％；女14例，占77.8％．门静脉纵向折叠移动范围1．8cm～4．2cm，平均折叠2．2cm者（1．8～2．4）占66．3％，平均折叠2．8cm（2．5～4．2）占33．7％．切除胰十二指肠后胰腺钩突入肠系膜上静脉段纵向折叠范围平均4．0cm，最长达5．2cm.结论这二类肿瘤切除术合并受浸血管切除在一定范围是可行的，为联合区域性整块切除术提供了临床解剖学支持     

Influence of different portal vein branches on hepatic encephalopathy during intrahepatic portal shunt via jugular vein

This letter is regarding the study titled ‘Targeted puncture of left branch of intrahepatic portal vein in transjugular intrahepatic portosystemic shunt (TIPS) to reduce hepatic encephalopathy’. Prior to the approval of TIPS dedicated stents (Viatorr stents) in China in October 2015, Fluency covered stents were typically used. As Fluency covered stents have a strong support force and axial elastic tension, a ‘cap’ may form if the stent is located too low at the end of the hepatic vein or too short at the end of the portal vein during surgery, leading to stent dysfunction. Since the blood shunted by the stent is from the main trunk of the portal vein, the correlation between the incidence of postoperative hepatic encephalopathy and the location of the puncture target (left or right portal vein branch) is worth discussion. Notably, no studies in China or foreign countries have proven the occurrence of left and right blood stratification after the accumulation of splenic vein and mesenteric blood flow in the main trunk of the portal vein in patients with cirrhotic portal hypertension.     

肝圆韧带重建门静脉/肠系膜上静脉的可行性探讨

目的探讨肝圆韧带重建门静脉／肠系膜上静脉的可行性。方法对4例实施胰十二指肠联合门静脉／肠系膜上静脉切除的患者．手术中用肝圆韧带重建切除的静脉。结果静脉切除长度3．5～6．5cm．重建切除静脉时利用肝圆韧带长度4．0～7．0cm,术中门静脉阻断时间30～126min,无手术死亡者。术后随访10～39个月。门静脉／肠系膜上静脉通畅,无血栓形成。结论在胰十二指肠联合门静脉／肠系膜上静脉切除术中利用肝圆韧带重建切除的静脉是可行的。     

Effects of partial portal vein arterialization on the hilar bile duct in a rat model

BACKGROUND: Liver revascularization is frequently required during the enlarged radical operation for hilar cholangio carcinoma involving the hepatic artery. Researchers have carried out a number of experiments applying partial porta vein arterialization (PVA) in clinical practice. In this study we aimed to establish a theoretical basis for clinical application o partial PVA and to investigate the effects of partial PVA on ra hilar bile duct and hepatic functions. METHODS: Thirty rats were randomly and equal...     

环孢霉素A对离体灌注肾内皮由来性舒张因子释放的影响

本文在建立稳定的离体灌注肾(IPK)装置基础上,利用一次性给予较大剂量环孢霉素A(CsA50μg/ml)引起IPK明显肾脏血流动力学障碍的模型,研究了内皮由来性舒张因子(EDRF)在CsA肾毒性发生中的意义。结果表明:正常IPK功能在本实验条件下能够稳定在2 h以上,CsA可以引起IPK RVR明显增高(P<0.05),RPF,GFR,UV,FF等明显下降(P分别小于0.01、0.05),SOD能通过加强EDRF的作用而改善由CsA引起的IPK血流动力学障碍,而EDRF抑制剂Hb可加强CsA的肾脏血流动力学效应。结果提示EDRF释放减少或灭活增多在CsA引起的IPK急性血流动力学障碍中可能具有重要意义。     

Case report: portal vein thrombosis associated with hereditary protein C deficiency: a report of two cases

Protein C deficiency is one of the causes of curable or preventable portal vein thrombosis. We report two patients of portal vein thrombosis associated with hereditary protein C deficiency. The first patient presented with continuous right upper quadrant pain and high fever. The abdominal sonography revealed normal liver parenchyma but portal vein and superior mesenteric vein thrombosis. Based on a 55% (normal 70-140%) plasma protein C level, he was diagnosed as having protein C deficiency. A trace of his family history showed that his elder brother also had protein C deficiency with a 50% plasma C level. Both patients received anticoagulant therapy. The younger brother showed good response. Unfortunately, the elder one suffered from recurrent episodes of variceal bleeding and received a life-saving splenectomy and devascularization. We herein remind clinicians that early screening and therapy are helpful in preventing late complications of protein C deficiency with portal vein thrombosis.     

Novel insights into the development of portal vein thrombosis in cirrhosis patients

The prognostic impact of portal vein thrombosis (PVT) in liver cirrhosis remains controversial among studies, primarily because the risk stratification of PVT is often lacking. A definition of clinically significant PVT should be proposed and actively improved. Moreover, the risk factors for the development of PVT in liver cirrhosis should be fully recognized to screen and identify high-risk patients. Currently, well-recognized risk factors include a reduced portal vein flow velocity, a worse liver function, splenectomy, liver transplantation, and factor V Leiden and prothrombin G20210A mutations. Novel risk factors include an increased flow volume of portosystemic collateral vessel, thrombopoietin receptor agnonists, and non-selective beta-blockers. In contrast to the traditional perspectives, the abnormalities of procoagulant and anticoagulant factors may not contribute to the development of PVT in liver cirrhosis. Further studies should explore the role of other risk factors, such as antiphospholipid antibodies, methylenetetrahydrofolate reductase C677T gene mutation, hyperhomocysteinemia, and myeloproliferative neoplasms.     

合并门静脉栓塞的肝移植受体术前诊断与术式研究

肝移植受体并门静脉栓塞原因通常分为门静脉血栓（PVT）和门静脉癌栓（PVTT）。术前准确诊断评价门静脉系统,对鉴别门静脉栓子性质及肝移植手术方式指导意义重大。本文对当前合并门静脉栓塞肝移植受体的术前诊断方法及伴PVT肝移植术中重建门静脉的术式进展作一简要综述。     

A pharmacodynamic model of portal hypertension in isolated perfused rat liver

AIM: To develop a pharmacodynamic model of portal hypertension from chronic hepatitis.METHODS: Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl₄-induced chronic hepatitis. At d₀, d₂₈, d₅₆ and d₈₄ of the process, the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump. The pressure (mmHg) was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension.RESULTS: At d₀, d₂₈, d₅₆ and d₈₄, the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y = 0.1732 + 0.3970/[1 + 10^{(-4.3061-0.4407 X)}], Y = -0.004934 + 0.12113/[1 + 10^{(-3.1247-0.3262 X)}], Y = 0.0104 + 0.2643/[1 + 10^{(-8.8462-0.9579 X)}], and Y = 0.01603 + 0.12107/[1 + 10^{(-5.1134-0.563 X)}]; the median effective concentrations were 1.69 × 10^-10 mol/L, 2.64 × 10^-10 mol/L, 5.82 × 10^-10 mol/L, and 8.24 × 10^-10 mol/L, respectively. The equations from the concentrations of acetylcholine used to relax the portal vein were Y = -0.4548 + 0.3274/[1 + 10^{(6.1538 + 0.5554 X)}], Y = -0.05391 + 0.06424/[1 + 10^{(3.8541 + 0.3469 X)}], Y = -0.2733 + 0.22978/[1 + 10^{(3.0472 + 0.3008 X)}], and Y = -0.0559 + 0.053178/[1 + 10^{(5.6336 + 0.5883 X)}]; the median effective concentrations were 8.40 × 10^-10 mol/L, 7.73 × 10^-12 mol/L, 5.98 × 10^-11 mol/L, and 2.66 × 10^-10 mol/L, respectively.CONCLUSION: A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.     

肝癌经皮门静脉时辰化疗生存期的初步观察

探讨不能手术切除的中晚期肝癌的治疗新途径,延长其生存期。对21例肝癌患者在TACE治疗后再经皮穿刺门静脉置管,采用微电脑控制的全自动注药盒每天在特定的时间向门静脉内注入顺铂(DDP)及5-氟尿嘧啶(5-Fu)进行时辰化疗并与对照组进行比较。结果表明:治疗组1年生存率41．69％,2年生存率27．79％,中位生存时间12．40月;对照组1年生存率23．33％,2年生存率10．00％,中位生存时间8．67月;经统计学分析,有显著性差异。提示门静脉置管时辰化疗联合TACE治疗中晚期肝癌疗效较为满意,值得进一步探索和研究。     

Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model

To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.     

Effects of 2-camphanone on canine portal vein blood flow and rat smooth muscle.

2-Camphanone is under clinical evaluation for alleviation of hemorrhoidal bleeding and inflammation. Reduced portal venous blood flow may distend, whereas improved portal venous blood flow may alleviate, hemorrhoidal vein distention. The effects of 2-camphanone on canine portal venous blood flow were investigated using pulsed Doppler flow techniques and on the spontaneous contractions of the isolated rat portal vein. Both intravenous (0.06, 0.2, and 0.6 mg/kg) and transdermal (6 mg/dog on the thigh) administration of 2-camphanone to dogs anesthetized with pentobarbital sodium increased portal venous flow velocity by 20%-30% without affecting femoral arterial blood flow, heart rate, or arterial blood pressure compared with vehicle-treated animals. Transdermal administration of 0.6, 2, and 6 mg of 2-camphanone, in a volume of 0.1 mL, to rats decreased the spontaneous contractions of the isolated rat portal vein in vitro. The data suggest that 2-camphanone exhibits a relatively selective effect on portal venous smooth muscle to reduce venous congestion and increase blood flow velocity. 2-Camphanone may be useful in the treatment not only of hemorrhoids, but also of esophageal reflux and portal hypertension.     

Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension

Introduction and objectivesLaparoscopic splenectomy (LS) is a supportive intervention for cirrhotic patients. However, its efficacy for patients with cirrhotic portal hypertension (CPH) still needs clarification. Studies indicated YKL-40 might be effective targets for treatment of splenomegaly, however deeper insights are unclear. The aim of this study was to investigate the effect of LS on the formation of portal vein thrombosis (PVT) and serum levels of a fibrosis marker, YKL-40, in patients with CPH.Materials and methodsA total of 80 patients who underwent LS and 30 healthy controls were investigated in this study. Serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA). Demographic characteristics including age and gender were recorded. Clinicopathological and laboratory examinations included the severity of esophageal varices and the presence of viral hepatitis. The liver function was assessed according to the Child–Pugh classification. The incidence of PVT before and after operation was also monitored.ResultsSerum YKL-40 was significantly increased in CPH patients, and was associated with Child–Pugh score and HBV infection. Furthermore, elderly patients had an increased risk for postoperative PVT. Higher serum YKL-40 was observed in patients with thrombus at postoperative 7, 14 and 21 days than those without thrombus.ConclusionsLS could reduce serum YKL-40 levels and PVT progression and was a useful treatment for patients <40 years of age with CPH.     

胃镜下聚桂醇注射联合套扎术治疗食管胃底静脉曲张的临床观察

目的探讨胃镜下聚桂醇注射联合套扎术治疗肝硬化食管胃底静脉曲张(EGV)的疗效和安全性。方法2016年1月至2018年1月,西安高新医院消化内科连续收治的肝硬化EGV患者作为研究对象,采用随机数字表法分为单纯套扎组和硬化联合套扎组,每组50例。单纯套扎组仅行胃镜下静脉曲张套扎术治疗,硬化联合套扎组术中行胃镜下静脉曲张套扎术治疗前先完成聚桂醇注射治疗。主要对比分析2组门静脉血流动力学测定结果,术后7 d、3个月、6个月的疗效评估结果,术后并发症发生情况。结果单纯套扎组和硬化联合套扎组术后门静脉血流速度[(23.87±2.57)cm/s比(26.52±2.71)cm/s,t=5.017,P<0.001]、血流量[(781.45±80.55)mL/min比(877.45±90.42)mL/min,t=5.606,P<0.001]比较差异均有统计学意义,且2组均明显高于术前(P均<0.05)。2组术后7 d治疗有效率分别为96%(48/50)和100%(50/50)(χ2=2.041,P=0.153),术后3个月分别为84%(42/50)和96%(48/50)(χ2=4.000,P=0.046),术后6个月分别为76%(38/50)和92%(46/50)(χ2=4.762,P=0.029)。2组术后并发症总体发生率分别为14%(7/50)和20%(10/50)(χ2=0.638,P=0.424)。结论胃镜下聚桂醇注射联合套扎术治疗肝硬化EGV安全有效,较胃镜下静脉曲张套扎术优势在于患者门静脉血流动力学改善更明显、疗效更稳定。