活体肝移植术后内脏血流动力学变化临床研究

目的 探讨门静脉高压症病人活体肝移植术后内脏血流动力学变化及其对侧支循环和术后肝功能的影响。方法 选取2006年12月至2008年6月因门静脉高压症在上海交通大学医学院附属瑞金医院行活体肝移植术18例病人,分别于术前,术后1、3、5、7d及1、3个月应用彩色多普勒超声监测病人门静脉血流平均速度（PBV）、门静脉血流量（PBF）和肝动脉阻力指数（HA-RI）变化,并与18例活体肝移植供体进行对照。应用计算机断层血管造影术分别于术后7、30和90d测量肝脏、脾脏体积大小,同时观察受体食管胃底曲张静脉变化。结果 移植术后受体组门静脉压力降低,但仍高于正常平均水平。术后PBF和PBV均明显升高,术后第1天PBF从术前（1081±278）mL/min升至（2171±613）mL/min,PBV从（15.0±5.7）cm/s升至（52.9±22.1）cm/s,其中脾动脉结扎组PBF低于不结扎组,但两组间差异无统计学意义（P＞0.05）;此后逐渐下降,但术后3个月仍高于供体组（P＜0.05）。供体组术后PBF与术前差异无统计学意义,而PBV从术前（23.7±7.2）cm/s增至（30.7±7.5）cm/s（P＜0.01）,1个月后恢复正常。术后移植物和残肝均迅速再生,3个月后分别增至（1426.2±203.4）mL和（1139.3±153.1）mL。受体组术后脾脏体积明显减小,但术后3个月脾脏体积仍远大于供体术前正常水平（P＜0.01）,而供体组术后脾脏体积较术前增加。术后早期食管胃底曲张静脉亦存在。结论 门静脉高压症病人活体肝移植术后门静脉血流呈高灌注状态,此变化与脾脏仍肿大有关。术后脾动脉结扎可有效预防移植物高灌注性损伤。     

门静脉高压症原位肝移植前后内脏血流动力学变化的临床研究

目的 研究门静脉高压症原位肝移植前后内脏血流动力学变化及其对脾功能亢进、侧支循环、术后肝功能恢复的影响.方法 2002年6月至2005年10月上海交通大学医学院附属瑞金医院外科共完成173例原位肝移植术.选取其中38例肝硬化门静脉高压症患者,分别于术前、术后1、3、5、7 d、1个月、6个月、1、2、3年行彩色多普勒超声检查,监测患者门静脉血流平均速度、门静脉血流量、肝动脉阻力指数等血流动力学指标和脾脏大小变化,并与8例急性重症肝炎患者及20名健康人进行对照,同时观察其对肝功能和食管胃底曲张静脉的影响.结果 肝硬化门静脉高压症患者术后门静脉血流平均速度从术前(13.7±4.2)cm/s升至(58.4±25.2)cm/s,门静脉血流量从(958±445)ml/min升至(3024±1207)ml/min,肝动脉阻力指数从0.65±0.11升至0.74±0.12,均明显高于急性重症肝炎组和正常对照组(P<0.05),门静脉血流平均速度和门静脉血流量分别于术后6个月、2年降至正常对照组水平.肝硬化门静脉高压症组术后脾功能亢进从术后第2天开始改善,至术后1个月完全恢复,但脾脏肿大在术后3年仍然存在.术后食管胃底曲张静脉亦明显改善.结论 肝硬化门静脉高压症患者原位肝移植术后内脏高血流动力学仍将长期存在,但并不影响脾功能亢进和食管胃底静脉曲张以及肝功能的恢复.     

肝硬化患者肠系膜上动脉血流动力学变化的观测

目的 通过肝硬化肠系膜上动脉（SMA）血流动力学观测，探讨肝硬化腹水形成机理。方法 采用彩色多普勒超声对50例对照组和80例肝硬化组SMA血流动力学进行测定。结果 肝硬化代偿期患、失代偿期患SMA的脉动指数（PI）和阻力指数（RI）均较正常对照组明显降低，但有腹水的肝硬化又较不伴腹水PI显降低，且有随食道静脉曲张的加重而降低的趋势。结论 肝硬化患早期即有内脏血流阻力的减低，SMA的高动力与腹水的形成、食道静脉曲张有关。     

血管内皮生长因子参与门静脉高压症内脏高动力循环

目的 检测血管内皮生长因子(vascular endothelial growth factor,VEGF)在门静脉高压症(portal hypertension,PHT)内脏血管中的表达变化,探讨其在内脏高动力循环中的作用及机制.方法 临床检测肝硬化PHT患者脾脏动脉内VEGF通路相关蛋白的表达.动物实验观察正常组(N组)7只大鼠和四氯化碳(CCl4)诱导的肝硬化门静脉高压症组(PHT组)7只大鼠的门静脉直径、门静脉血流速度(portal vein blood flow velocity,PBV)、门静脉血流量(portal vein blood flow,PBF)和门静脉压力(portal vein pressure,PP)以及离体肠系膜微动脉对去甲肾上腺素(norepinephrine,NE)的反应性变化.通过SU5416选择性抑制VEGF通路后,对比离体肠系膜微动脉收缩反应性的变化以及肠系膜动脉内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)活化程度的变化.细胞实验中通过原代培养动脉内皮细胞进行体外实验,验证VEGF对eNOS活化的影响.结果 ①肝硬化PHT患者脾动脉VEGF表达明显升高.②动物实验中门静脉直径在N组和PHT组之间差异无统计学意义,PHT组PBV和PBF明显低于N组,SU5416对PHT组PBV及PBF无明显改善作用.③PHT组PP水平明显高于N组,SU5416对PHT组PP无明显降低作用.④PHT组肠系膜微动脉对NE的反应性明显降低,EC50值明显增大,SU5416能部分改善这种低反应性.⑤PHT组肠系膜动脉VEGF、VEGFR-2、eNOS和p-eNOS的蛋白表达较N组明显上调,SU5416能明显降低VEGFR-2与表达和eNOS的活化.⑥体外实验证实,VEGF可促进eNOS的活化.结论 肝硬化PHT内脏动脉中过度生成的VEGF部分通过促进eNOS表达和活化的方式降低内脏动脉对NE的反应性,参与内脏高动力循环的形成.     

猪背驮式原位肝移植的手术技巧

目的　改进和完善猪背驮式原位肝移植 (PBOLT)手术 ,为临床背驮式原位肝移植提供帮助。方法　根据猪的解剖和血流动力学特点 ,采用缝扎法切除受肝 ,减少输血量以减轻门静脉淤血。结果　实施猪PBOLT 1 6次 ,术后存活 1 3头 ,手术成功率 81 3%。平均无肝期 34min± 1 2min ,平均手术时间 7h± 1h。结论　改进和完善手术技巧 ,减轻门静脉系统淤血是PBOLT成功的关键     

热休克蛋白90在门静脉高压症内脏高动力循环中的作用

目的:研究热休克蛋白90(heat shock protein 90,HSP 90)在门静脉高压症(portal hypertension,PHT)内脏动脉中的表达变化,探讨其在高动力循环形成中的作用及可能的机制。方法:检侧四氯化碳(CCl4)诱导的肝硬化PHT组(n=7)和对照组(n=7)大鼠的门静脉血流速度(portal vein blood flow velocity,PBV)、门静脉直径、门静脉血流量(portal vein blood flow,PBF)和门静脉压力(portal vein pressure,PP),离体肠系膜微动脉对去甲肾上腺素(norepinephrine,NE)的反应性、HSP 90特异性抑制剂格尔德霉素(geldanamycin,GA)对离体肠系膜微动脉收缩反应的影响以及肠系膜动脉内HSP 90和内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)的蛋白表达变化。结果:①PHT组大鼠PBV和PBF明显低于对照组,门静脉直径在PHT组与对照组之间无统计学差异,GA对PHT组PBV及PBF无明显改善;②PHT组大鼠PP明显高于对照组,GA对PHT组PP并无明显降低作用;③PHT组大鼠肠系膜微动脉对NE的收缩反应性明显降低,50%作用浓度明显增大,GA能部分改善这种低反应性;④PHT组大鼠肠系膜动脉内HSP 90和eNOS的蛋白水平较对照组明显上调,GA明显降低PHT组肠系膜动脉HSP 90表达的同时,也降低了eNOS的表达。结论:CCl4诱导肝硬化PHT肠系膜动脉中过度生成的HSP 90可能是通过增加eNOS的表达降低肠系膜动脉对NE的反应性参与内脏高动力循环的形成。     

肝硬化病人肾血流变化的临床研究

目的 研究肝硬化患者肾脏血液动力学的变化。方法 对49例肝硬化病人采用彩色多普勒超声测定肾叶间动脉及弓形动脉搏动指数(PI)、阻力指数(RI)及收缩期最高峰值／舒张期最低峰值(PS／PD)等指数，并同时监测患者的血内皮素情况。结果 肝功能越差，搏动指数和阻力指数越高，尤以RI为著；随腹水量的增加，肝硬化病人的PI、RI等亦有明显增高。肝硬化血内皮素(ET)的增高与PI及RI增高密切相关。结论 通过多普勒超声发现肝硬化患者肾血流与肝功能有直接相关性，肝硬化腹水和肾血流亦有相关性，而顽固性腹水PI、RI的演变可能有助于早期发现肝肾综合征(HRS)；血内皮素水平在肝硬化病人中明显增高。且与肾血管阻力的增加呈正相关，因而内皮素可能是参与肝硬化病人肾血管收缩的重要活性因子。     

肝硬化鼠肝移植后早期全身和内脏血流动力学的变化

目的 观察正常鼠肝移植及及肝硬化鼠肝移植术早期全身和内脏血流动力学的变化。方法 实验动物随机分为正常鼠（NL,10只）、肝硬化鼠（IHPH,10只）、正常鼠肝移植（NL－OLT,9只）、肝硬化鼠肝移植（IHPH－OLT,16只）组。分别采用放射性微球法行血流动力学研究。结果 NLOLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义。IHPH及IHPH－OLT 3d,7d组心输量和内脏血流量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低。内脏血流动力学紊乱较全身明显。结论 肝硬化鼠肝移植后的血流动力学紊乱可能与移植前已存在的病理生理因素有关。     

原位肝移植术后肾血流动力学研究

目的：探讨原位肝移植（OLT）受者肾的血流动力学变化及其相关因素。方法：20例因肝硬化行OLT患者，分别于术前、术后7d，30d，6个月及1年时应用彩色多普勒血流显像仪（CDFI）测定肾动脉血流阻力指数（RI）、测定血清肌酐（Cr）值，并与10例正常人进行对照。 结果：术后早期OLT受者RI与血清Cr在均升高（P<0.01）,至术后1年可逐渐恢复正常（P>0.05）。结论：原位肝移植术后肾血流动力学大都在1年内恢复正常，术前肾的异常及术中血流动力学变化可导致术后肾功能不全，但术后长期的肾功能改变则主要与环孢菌素（CsA）等的作用有关。     

选择性脾胃区减断分流术对肝脾血流动力学的影响

目的 探讨肝硬化门静脉高压患者行选择性脾胃区减断分流术(SDDS-GSR)后肝脾血流动力学的改变及临床意义.方法 前瞻性收集41例行SDDS-GSR术治疗患者的超声检查资料,按术前、术后2周及术后1年分为3期,并以21例正常体检患者为对照进行研究.结果 (1)脾脏厚度在术后2周(47±8)mm及术后1年(46±8)mm较术前(60±9)mm显著减小(P<0.01).(2)术后2周门静脉直径(1.13±0.19)cm较术前显著变窄(P<0.01),脾动脉直径(0.49±0.08)cm较术前显著变窄(P<0.05),肝动脉直径(0.40±0.07)cm较术前显著增宽(P<0.05).术后1年门静脉直径(0.89±0.17)cm均较术前显著变窄(P<0.01).(3)术后2周门静脉血流量(649±294)ml/min和脾动脉血流量(446±254)ml/min较术前显著减小(P<0.01),肝动脉血流量(612±295)ml/min较术前显著增加(P<0.01).术后1年肝动脉血流量(401±152)ml/min与术前和正常组比较差异均无统计学意义(P>0.05).结论 肝硬化门静脉高压症患者肝脾血流动力学参数发生异常变化;SDDS-GSR有助于纠正肝硬化门静脉高压症患者肝脾血流动力学的紊乱状态.     

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??Clinical study on splanchnic hemodynamic changes after living donor liver transplantation for patients with portal hypertension JIANG Shui-ming, ZHOU Guang-wen, SHEN Chuan, et al. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Corresponding author ??ZHOU Guang-wen, E-mail??gw_vrai@yahoo.com.cn
Abstract Objective To study the splanchnic hemodynamic changes after living donor liver transplantation (LDLT). At same time, the effect of such changes on collateral circulation and postoperative liver function was evaluated too. Methods Between 2006 and 2008, in 18 patients with portal hypertension underwent LDLT, the following parameters were measured preoperatively and postoperative days 1, 3, 5, 7; and 1, 3 months after LDLT with Color Doppler sonography: portal blood flow volume (PBF), portal blood flow mean velocity (PBV), hepatic artery resistance indexes (HA-RI). The same parameters were measured in 18 living donors as contrast. Postoperative graft and spleen volume were estimated by computed tomography. Results In recipient group, portal venous pressure was decreased, but was higher than normal value after LDLT. PBF and PBV increased and achieved peak value in first day after LDLT (from 1081±278 mL/min to 2171±613 mL/min and from 15±5.7 cm/s to 56±22.1 cm/s, respectively, P<0.01). Although a progressive reduction of PBF and PBV was observed during the follow-up, until 3 months after LDLT, PBF and PBV were significantly greater than donor group (P<0.05). In donor group, although PBF had no change after LDLT, PBV increased (from 23.7±7.2 cm/s to 30.7±7.5 cm/s, P<0.05), and returned to normal after 1 month. Graft and residual liver regenerated rapidly after LDLT. Graft and residual liver volume reached 1426.2±203.4mL and 1139.3±153.1mL respectively. A clear and rapid improvement in splenomegaly was presented in recipient group, whereas spleen size increased postoperative in donor group. Conclusions A high portal flow was present in cirrhosis with portal hypertension after LDLT.The possible causes for this can be persistence of considerable splenomegaly. Splenic artery is effective management modality for preventing portal hyperperfusion injury.     

一氧化氮在大白鼠肝硬变门静脉高压症中的作用

为探讨一氧化氮在肝硬变形成过程中的作用，我们通过观察一氧化氮合成酶在正常鼠和肝硬变、门静脉高压症大鼠肝脏的分布，同时测定了门静脉血亚硝酸盐／硝酸盐离子水平，并监测两组动物的血液动力学指标。结果发现：正常鼠肝脏的一氧化氮合成酶染色阴性，肝硬变鼠肝脏的再生假小叶内肝细胞的一氧化氮会成酶染色为强阳性；两组动物门静脉血的亚硝酸盐／硝酸盐离子的浓度分别为９．８±３．２ｕｍｏｌ／Ｌ，２６．７±６．８ｕｍｏｌ／Ｌ，差异有极显著性意义（Ｐ＜０．０１）；肝硬变大鼠的门静脉压力、门静脉血流量显著高于正常大鼠（Ｐ＜０．０５），而内脏血管阻力显著低于正常大鼠（Ｐ＜０．０５）。结果提示：一氧化氮在肝细胞的损伤及肝硬变门静脉高压的血液动力学改变中起重要作用。     

Effects of carbon dioxide pneumoperitoneum on hemodynamics in cirrhotic rats

Background: The aim of our study was to investigate the effect of carbon dioxide pneumoperitoneum on systemic and splanchnic hemodynamics in cirrhotic rats. Methods: Sprague–Dawley rats (n = 80) were used in this study. Liver cirrhosis was induced by thioacetamide administration intraperitoneally (200 mg/kg body weight, twice a week for 16 weeks). The radioactive microsphere method was used to measure systemic and regional hemodynamic parameters before, 1 h after the start, and 1 h after the release of pneumoperitoneum. Results: Splanchnic blood flow and cardiac index were significantly depressed during pneumoperitoneum in liver cirrhosis and control groups, but no significant differences were seen between the two groups. In both groups, portal venous inflow decreased and hepatic arterial blood flow increased significantly during pneumoperitoneum. However, during pneumoperitoneum, total hepatic blood flow as a percentage of its value before pneumoperitoneum was lower in cirrhotic rats (71.0%) than in control rats (91.9%) (p <0.05, Mann–Whitney U-test). Conclusions: Carbon dioxide pneumoperitoneum markedly decreases total hepatic blood flow in cirrhotic rats due to the impaired hepatic arterial buffer response. Liver function should be carefully controlled in cirrhotic patients after laparoscopic surgery with pneumoperitoneum.     

原位肝移植术后脾功能亢进的恢复

摘要：目的 观察原位肝移植术后脾功能亢进（脾亢）的变化，探讨肝移植对脾亢的影响。 方法 收集2年半内接受肝移植手术、符合入选条件的14例患者的资料，分析手术前后各时点的脾脏厚度，血小板（PLT）和白细胞（WBC）计数， 以及术后门静脉流速的变化规律。 结果 术后血WBC和PLT计数1个月内恢复正常，脾脏厚度术后1个月下降约17%，此后1年内保持稳定；门静脉流速1个月内明显升高，以后逐步缓慢下降；血WBC，PLT，术后门静脉流速等3个指标和脾脏厚度均具有明显相关性。 结论 术后门静脉的高流速归因于脾静脉回流的持续增高；术前WBC和PLT减少的主要原因是脾脏体积的增大；术后脾亢的恢复取决于脾脏体积的回复程度。脾亢患者行肝移植手术时无需行脾脏切除术。     

Effects of rapid paracentesis on right ventricular-arterial coupling in liver transplantation

BACKGROUND: In cirrhotic patients intra-abdominal pressure (IAP) changes markedly modify splanchnic and systemic hemodynamics. Previous studies have evaluated the effects of increased IAP on steady-state cardiac performance, showing that right ventricular (RV) function becomes more depressed than that of the left ventricular. We sought to evaluate the effects of paracentesis on RV function and ventricular-arterial coupling among cirrhotics undergoing liver transplantation (OLT). METHODS: Twelve cirrhotic patients undergoing OLT underwent hemodynamic profiles before and 5 minutes after paracentesis, employing a right ventricular ejection fraction catheter in the pulmonary artery. We studied heart rate, systolic pulmonary artery pressure, central venous pressure (CVP), stroke volume index (SVI), RV end-diastolic volume index (RVEDI), and RV ejection fraction. In addition RV stroke work index (RVSWI), RV end-diastolic compliance (RVEDC), RV end-systolic elastance (Ees), pulmonary artery effective elastance (Ea), and RV coupling efficiency (Ees/Ea ratio) were calculated employing standard formulas. RESULTS: After removal of mean ascites volume of 5.6 +/- 2.2 L (range 4.0 to 8.04 L), SVI, RVEDI, RVSWI, and RVEDC were significantly increased and conversely CVP, Ees, and Ea were decreased with an ea/ea ratio unchanged. CONCLUSIONS: Before paracentesis Ees/Ea is preserved by increased of RV contractility; after paracentesis the coupling was maintained.     

Splanchnic circulation following coeliac plexus block

Both the capacitance vessels and the resistance vessels of the splanchnic area are innervated by the sympathetic nerve fibers. We investigated the effect of abdominal visceral sympathectomy on splanchnic circulation, and the effect of altered splanchnic circulation on systemic circulation in ten mongrel dogs. Abdominal visceral sympathectomy was induced by coeliac plexus block with 1 ml/kg (body weight) of 1 % lidocaine infiltrated around the coeliac artery. Comparison was made with infiltration of physiologic saline of the same volume. The saline infiltration caused no significant changes in the hemodynamic parameters of systemic and splanchnic circulation. Mean arterial pressure decreased significantly from 18.2 ±2.0 to 14.4±1.9 kPa following the coeliac plexus block, with a concomitant decrease in the cardiac index from 2.63 ± 0.46 to 2.30 ± 0.54 1 × min^-1 × m^-2, while systemic vascular resistance was unchanged. Portal vein blood flow, hepatic artery blood flow and, therefore, splanchnic blood flow decreased by 8 to 17%. Portal vascular and hepatic artery resistances were not affected by abdominal sympathectomy. It was concluded that the capacitance vessels in splanchnic circulation are dilated during abdominal sympathetic denervation, causing a blood shift from systemic to splanchnic circulation. On the other hand, the resistance vessels in splanchnic circulation are affected little by abdominal visceral sympathectomy.     

血管活性物质在肝硬化肝移植后高血流动力学中的作用

目的：探讨内源性血管活性物质在肝硬化鼠肝移植后设备在流动力学中的作用,方法：雄性SD大鼠随机分为四组,正常对照组（NL）,肝硬化组（IHPH）,正常鼠肝移植组（NL－OLT）和肝硬化地移植组（IHPH－OLT）,IHPH－OLT鼠又分为术后3天（A组）和7天（B组）两个亚组,IHPH模型肌注CCI4制备,大鼠OLT模型采用三袖套法,血流动力学研究采用放射性微球注射技术,血浆胰高糖素（Glu),一氧化氮（NO）,前列环环素（PGI2）,血栓素（TXA2）以及内皮素（ET）浓度用放射免疫法测定,结果：NL－OLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义（P＞0．05）,与NL鼠比较,NL－OLT鼠的NO和PGI2均无明显变化,而Glu,ET 和TXA2水平显著地升高（P＜0．05）,IHPH,IHPH－OLT A,B鼠均具有全身和内脏高血流动力学特征,其高动力循环的程度和血管扩张物质NO和Glu增加的程度均是IHPH＞IHPH－OLTA＞IHPH－OLTB鼠的PGI2显著地高于NL鼠,IHPH－OLTA、B鼠的PGI2显著地低于IHPH鼠（P＜0．05）,而HPH－OLTB鼠与NL鼠比较已无显著差异,血管收缩物质ET和TXA2在肝硬化肝移植术后均有不同程度升高,结论：肝移植术本身并不导致术后高血流动力学的发生,血管扩张物质NO和Glu,尤其是NO在IHPH以及IHPH－OLT鼠的高动力循环中起重要作用,肝硬化肝移植后早期依然存在的高动力循环是术前引起高血流动力学发病因子升高的原因未消除的结果。