门脉高压鼠血浆前列环素过多产生机制的实验研究

探讨门脉压力升高和门体分流在前列环素(PGI_2)升高中的作用。方法:36只雄性SD大鼠随机分为4组:肝前型(PHPH,n=8)和肝内型门脉高压(IHPH,n=9)、端侧门腔分流(PCS,n=8)以及手术对照组(SO,n=11)。模型制备后两周:(1)测游离门脉压(FPP);(2)应用同位素微球技术研究全身及内脏血流动力学;(3)从股动脉采集血样,用放射免疫法测血浆6-酮-前列腺素F_1α(6-keto-PGF_1α)浓度。结果:心脏指数(CI)和内脏血流量(PVI)是PCS>PHPH>IHPH>SO鼠。门体分流率(PSS)是PCS>PHPH>IHPH。在PHPH、IHPH、PCS和SO鼠,血浆6-keto-PGF_1α的浓度(ng/ml)分别为6.93±2.43、5.09±2.27、2.36±1.01和1.56±0.61,前3组鼠均显著高于SO鼠(P<0.05),且PHPH鼠和IHPH鼠均显著高于PCS鼠(P<0.05)。血浆6-keto-PGF1_1α浓度与FPP值呈非常显著性正相关(r=0.67,P<0.001)。结论:在门脉高压中,PGI_2升高主要是门脉压力升高刺激其在血管内皮细胞的合成增加,而门体分流和肝功能减退起次要作用。此外,本研究结果并不支持PGI_2参与门脉高压高血流动力学的发生。     

Vasopressin and splanchnic shunting. A quantitative comparison.

To analyze the relationship between the splanchnic and systemic effects of vasopressin and to measure its efficacy in lowering portal pressure relative to what can be accomplished by zero gradient shunting, intraoperative measurements of cardiac output and relevant pressures were made in 30 patients undergoing selective or total shunts. Vasopressin caused a significant increase in systemic vascular resistance and pulmonary capillary wedge pressure, but an insignificant overall reduction in cardiac index (CI). However, in ten patients the decrease in CI exceeded 20%, suggesting a subpopulation of especially susceptible individuals. High initial CI, age, pre-existent heart disease, and severity of cirrhosis did not predict greater vulnerability. Adding an infusion of nitroprusside regularly reverted CI to control levels, regardless of the extent of cardiac output depression. Vasopressin was 38% as effective as a subsequent shunt in reducing splanchnic venous pressure. The portal hypotensive action bore no relationship to CI, but the pressure decrease caused by vasopressin was predictive of the reduction that could be achieved by shunting. The effects of the two types of shunts on systemic hemodynamics were minor and remarkably similar.     

Role of prostacyclin in the splanchnic hyperemia contributing to portal hypertension.

To determine the possible role of prostacyclin (PGI2) as a mediator of the splanchnic hyperemia seen with portal hypertension, the portal and mesenteric hemodynamics in normal and portal hypertensive rabbits were studied before and after cyclo-oxygenase blockade. Three weeks after partial portal vein ligation, splenic pulp pressure was elevated from 4.3 +/- 0.9 to 9.8 +/- 0.8 mmHg (p less than 0.01). Mesenteric blood flow increased from 77.0 +/- 4.7 ml.min-1.100 g-1 to 99.1 +/- 5.19 ml/min-1/100 g-1. Mesenteric vascular resistance fell from 0.82 +/- 0.6 mmHg/ml-1/min-1 to 0.49 +/- 0.07 mmHg/ml-1/min-1 (p less than 0.01). These hemodynamic changes were associated with a 27.3 +/- 0.2% rise in systemic arterial levels of PGI2 (p less than 0.01) and were substantially ameliorated by cyclo-oxygenase blockade with indomethacin. The effects of indomethacin blockade were reversed by exogenous PGI2. Moreover, in normotensive rabbits, infusion of PGI2 reproduced the splanchnic hyperemia and caused a very small but significant increase in portosystemic shunting. These findings support the previously proposed concept that splanchnic hyperemia may contribute to the maintenance of chronic portal hypertension. Furthermore, they suggest that this effect may be partially mediated by splanchnic PGI2 production.     

Evidence for role of prostacyclin as a systemic hormone in portal hypertension

The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals. In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics. These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT. In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension.     

肝硬变门脉高压症病人门体分流术后血浆前列环素含量变化的研究

用放射免疫分析方法观察了１５例肝炎后肝硬变门静脉高压症病人血中前列环素含量的变化。结果显示，门体分流术后，门静脉及周围静脉血中前列环素含量分别下降了４９．６３％（Ｐ＜０．０１）和２１．６４％（Ｐ＜０．０５）。门静脉血中前列环素含量的下降与门静脉压的下降呈正相关（ｒ＝０．７４，Ｐ＜０．０５）。表明肝硬变病人体内前列环素含量的增加主要是由于内脏血管内皮细胞合成增加所致，前列环素对门静脉高压症的形成以及维持其高压状态持续存在起一定作用。     

肝前型门静脉高压大鼠门体分流及循环动力学的实验研究

作者使用放射性微球技术，观察了３１只大鼠不同程度门静脉缩窄后血流动力状态及门体分流量和门静脉压力之间的关系。结果显示，肝前型门静脉高压大鼠存在显著的高循环动力状态：心输出量及心脏指数明显升高，平均动脉压降低，伴有外周血管阻力下降；内脏血流量增加，血管阻力下降；门体分流量明显增加，并与门静脉压力的升高两者之间存在明显正相关Ｙ＝２６．１４＋５．３２Ｘ（ｒ＝０．７６，Ｐ＜０．００１）。作者认为，全身及内脏血流增加是维持实验动物门静脉高压状态的主要因素。     

Mesoatrial shunt hemodynamics

Hemodynamic profiles were obtained for patients with portal hypertension secondary to the Budd-Chiari syndrome who underwent mesoatrial shunting procedures. In contrast to the well-known hyperdynamic, low-resistance state of chronic cirrhosis, patients with the Budd-Chiari syndrome had normal cardiac index and systemic vascular resistance values before anesthesia and surgery. Opening the mesoatrial shunt produced a 46% (p less than 0.01) increase in cardiac index and a 38% (p less than 0.01) decrease in overall systemic vascular resistance. Right atrial pressure and pulmonary capillary wedge pressures were sharply increased--by 5.3 mm Hg and 4.7 mm Hg, respectively (p less than 0.01). A mathematical model was developed to assess the cause of the observed changes in systemic vascular resistance. The model suggests that the hemodynamic changes seen with shunt opening are unlikely to be the result of shunt effects alone and that dilatation of peripheral vascular beds is probable. Thus shunting converts the normal systemic vascular resistance and cardiac index of patients with the Budd-Chiari syndrome to the high-output, low-resistance state seen in patients with chronic cirrhosis. Although the physiology is complex, we conclude that the data are consistent with release, by the shunting process, of a systemic vasodilator.     

门静脉高压症手术前后血流动力学改变及临床意义

采用彩色多普勒血流显像（ＣＤＦＩ）．对门静脉高压症手术前后门静脉血流动力学进行观测和对比分析。结果表明：（１）肝硬变门静脉高压症的门、脾静脉内径和血流量显著扩张和增加，和正常人比较差异有显著性（Ｐ＜０．０１）．门静脉血流量增加与脾静脉血流量增加呈正相关；（２）断流术后．门静脉内径变窄和血流量明显减少，与对照组比较差异有显著性（Ｐ＜０．０１）；（３）断流加脾肾分流联合术后，门静脉内径变窄明显大于断流术，但两术式后门静脉血流量减少差异无显著性、结果认为．断流术和断流加脾肾分流联合术均为治疗肝硬变门静脉高压症较合理的术式。     

门脉高压症患者门体分流术后血前列环素水平变化的临床观察

初步探讨临床门脉高压症患者门体分流术后血前列环素水平的变化。方法:15例(45±12岁)乙型肝炎后肝硬化(经病理证实)门脉高压症患者中,6例行门腔静脉人造血管搭桥分流术,9例行脾肾静脉分流术。于开腹后、探查前和术后3天分别抽取股动、静脉和胃网膜右静脉血各3ml,经处理后,取血浆标本保存,3周内用放免法测定其前列环素含量。采用自身对照t检验方法作统计学分析。结果:术后门静脉和周围静脉血中前列环素含量明显低于术前含量(P <0.01和P<0.05),而且门静脉血中前列环素含量下降值与门静脉压力下降值呈正相关(r=0.74,P<0.05)。结论:肝硬变门脉高压症患者在行门体分流后,其门静脉外周静脉血中前列环素含量随门静脉压力下降而下降,并不因门体分流术后分流量的增加而升高。     

Effect of portasystemic shunt operations on hepatic portal perfusion

We recently developed a radiocolloid technique for quantifying the fraction of superior mesenteric venous blood that bypasses liver sinusoids through extra- and intrahepatic collateral vessels. In the present investigation we applied this method, which is performed in conjunction with visceral angiography, to the assessment of patients with portal hypertension before and after surgical construction of portasystemic shunts. The mean corrected shunt index was 0.89 in 27 preoperative patients, and 48 percent of the patients had no evidence of sinusoidal perfusion by superior mesenteric venous blood (shunt index greater than 0.95). Sinusoidal perfusion was absent in five patients with residual hepatic portal flow by angiography, indicating that they had a high degree of intrahepatic shunting. Hepatic portal perfusion was preserved in 80 percent of patients after distal splenorenal shunt, and the corrected shunt index was significantly smaller after this procedure than after portacaval and interposition shunts. Three patients with no sinusoidal perfusion by superior mesenteric blood preoperatively had restoration of portal flow after distal splenorenal shunt. Five patients undergoing portacaval and interposition shunts had no evidence of portal sinusoidal perfusion by the radiocolloid technique either before or after the operative procedure.     

Computer analysis of portal hemodynamics after small-diameter portacaval H-grafts: the theoretical basis for partial shunting

We have previously reported on the clinical results of partial shunting using small-diameter portacaval H-grafts. In this study, we defined the theoretical basis for partial shunting using the Wheatstone bridge model of the splanchnic circulation. The model was modified to include a variable resistance for a portacaval shunt and was programmed as a computer simulation. We calculated portal flow as a function of shunt resistance to determine the resistance necessary to maintain prograde portal flow in patients with portal hypertension. The resistance of 8- and 10-mm portacaval H-grafts, as positioned clinically, was determined using a laboratory apparatus. The experimentally derived values for resistance were inserted into the graph of portal flow predicted by the computer program. Portacaval H-grafts 8 mm in diameter should produce prograde portal flow, 10-mm H-grafts should be borderline, and shunts larger than 10 mm should routinely result in reversed flow. These predictions were confirmed by clinical observations in 29 patients undergoing portacaval H-grafts.     

Long-Term Hemodynamic Effects of Portocaval Shunt and Sugiura Procedure in Patients with Cirrhosis

Systemic and splanchnic hemodynamics were studied before and six months after a portal systemic shunt (n=6) or a Sugiura procedure (n=9) in 15 patients with cirrhosis and a past history of variceal bleeding. Hepatic blood flow was estimated by hepatic extraction and clearance of continuous indocyanine green infusion. Azygos blood flow was measured with a continuous thermodilution catheter. After portocaval shunt, the cardiac index increased significantly from 4.0±1.4 to 5.4±0.8 l/min m2 (p<0.05), the hepatic venous pressure gradient and hepatic blood flow were significantly decreased from 21±3 to 13±5 mm Hg (p<0.05) and from 1.20±0.35 to 0.37±0.16 l/min (p<0.05) respectively. The decrease in azygos blood flow was not significant (0.51±0.31 vs 0.25±0.33 l/min; p=0.1). After Sugiura procedure, there was no significant change in cardiac index, hepatic venous pressure gradient, hepatic blood flow or azygos blood flow. This is the first study to show the long-term maintenance of splanchnic and systemic hemodynamics in patients with cirrhosis after Sugiura procedure. The absence of long-term hemodynamic alterations could explain the absence of encephalopathy after this procedure.     

Splanchnic Haemodynamics and Vasoactive Agents in Experimental Cirrhosis

It is well known that portal hypertension is associated with a hyperdynamic systemic circulatory state. This study measures systemic and splanchnic haemodynamics in an experimental rat model of hepatic cirrhosis. It also investigates the association between haemodynamic changes in cirrhotic animals and circulating levels of the vasoactive hormones glucagon and vasoactive intestinal polypeptide (VIP). Splanchnic blood flow was significantly increased in the cirrhotic group (13.2 ± 1.3 vs. 9.2 ± 1.6 ml/min, P < 0.05). Circulating levels of glucagon and VIP were two and five fold increased respectively in cirrhotic animals compared to controls. There was a strong correlation between portal pressure and glucagon levels in the cirrhotic group (r = 0.85). Raised splanchnic blood flow is partly responsible for elevated portal pressure in this model and this rise may be humorally mediated.     

Budd-Chiari syndrome: current management options

OBJECTIVE: To assess the outcomes of current treatment strategies for Budd-Chiari syndrome. SUMMARY BACKGROUND DATA: Budd-Chiari syndrome, occlusion or obstruction of hepatic venous outflow, is a disease traditionally managed by portal or mesenteric-systemic shunting. The development of other treatment options, such as catheter-directed thrombolysis, transjugular portosystemic shunting (TIPS), and liver transplantation, has expanded the therapeutic algorithm. METHODS: The authors reviewed the medical records of all patients diagnosed with Budd-Chiari syndrome at the Johns Hopkins Hospital during the past 20 years. RESULTS: A total of 54 patients were identified: 13 (24%) male patients and 41 (76%) female patients, ranging in age from 2 to 76 years (median 33 years). Twenty-one (39%) had polycythemia vera, 3 (5.6%) used estrogens, 11 (20%) had a myeloproliferative or coagulation disorder, and in 7 (13%) the cause remained unknown. Forty-three patients were treated with surgical shunting, 24 mesocaval and 19 mesoatrial. Actuarial survival rates at 1, 3, and 5 years after shunting were 83%, 78%, and 75%, respectively. Of 33 patients surviving more than 4 years, 28 (85%) had relief of clinical symptoms. Five patients required shunt revision and eight had radiologic procedures to maintain shunt patency. Primary and secondary shunt patency rates were 46% and 69% respectively for mesoatrial shunts and 70% and 85% respectively for mesocaval shunts. Clot lysis was successful as primary treatment in seven patients. TIPS was performed in three patients, one after a failed mesocaval shunt. During an average of 4 years of follow-up, these patients required multiple procedures to maintain TIPS patency. Six patients underwent liver transplantation. Of these, three had previous shunt procedures. Five of the transplant recipients are alive with follow-up of 2 to 9 years (median 6). CONCLUSIONS: Both shunting and transplantation can result in a 5-year survival rate of at least 75%, and other treatment modalities may be appropriate for highly selected patients. Optimal management requires that treatment be directed by the predominant clinical symptom (liver failure or portal hypertension) and anatomical considerations and be tempered by careful assessment of surgical risk.     

Portal venous decompression with H-type mesocaval shunt using autologous vein graft: a North American experience

BACKGROUND/PURPOSE: Portal hypertension in children often is caused by prehepatic venous obstruction or intrahepatic fibrosis without cirrhosis. This situation is uniquely amenable to shunting; this report details the experience of 3 North American centers with an H-type mesocaval shunt using autologous vein, which has been widely used in European centers. METHODS: Retrospective chart review was conducted of records from 1980 through 1999 at 3 North American institutions. Charts were reviewed for etiology of portal hypertension, diagnostic workup, preoperative management, operative results and complications, postoperative shunt patency, patient well-being, and eventual need for liver transplantation. RESULTS: Twenty patients were identified with prehepatic causes of venous obstruction undergoing shunt therapy. Eleven had portal venous thrombosis or cavernous transformation. Of these, 3 had umbilical catheters placed in the neonatal period. Five children had American-Indian cirrhosis, 1 had congenital hepatic fibrosis, and 3 had hepatic fibrosis associated with polycystic kidney disease. Patients presented at a median age of 3.7 years and underwent follow-up for an average of 4.3 years after surgery. These patients had an average of 3.6 bleeding episodes, (with 3.9 attempts at sclerotherapy) and received 3 units of blood preoperatively. Average age at operation was 8 years, average weight was 30 kg, and perioperative blood requirement was 200 mL. In general, patients did well postoperatively; 2 patients required reoperation for lymphatic leaks, and there was 1 death caused by a leaking G-tube, unrelated to shunt functioning. Two patients had transient encephalopathy postoperatively, and 1 patient had severe pancreatitis. All shunts remain patent, with good function and no further bleeding. CONCLUSIONS: These results are encouraging, and we would suggest that the H-type mesocaval shunt utilizing autologous vein be considered for wider use in pediatric patients with prehepatic cause of portal hypertension. An algorithm for the work-up of pediatric patients with variceal bleeding is presented, with the recommendation that shunt surgery be considered early in patients with a prehepatic or fibrotic causes of portal hypertension.     

Severe fatty change of the graft liver caused by a portosystemic shunt of mesenteric varices

Portosystemic shunt is a common complication in patients with portal hypertension. Mesenteric varix is one of the collaterals that can cause post-transplant liver dysfunction. In this case report, a 45-year-old woman underwent living relative donor liver transplantation for alcoholic cirrhosis. Although the early postoperative course was uneventful, she was readmitted for treatment of liver hypofunction. Fatty change in the graft liver was confirmed by histopathology of the biopsy specimen. The venous phase of a superior mesenteric angiogram revealed large-caliber mesenteric varices comprising portosystemic venous shunts. Surgery was performed to ligate the shunts. The intraoperative color Doppler ultrasonography showed hepatofugal portal blood flow, which was corrected to hepatopetal blood flow by clamping the shunt vessels. The portal pressure was moderately elevated from 13.6 cm to 21.8 cm H(2)O. Two shunt vessels were ligated and divided. Her liver function returned to nearly normal thereafter. We recommend that descending collaterals be divided during liver transplantation.     

Management of Major Portosystemic Shunting in Small-for-Size Adult Living-Related Donor Liver Transplantation with a Left-Sided Graft Liver

PURPOSE: We investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver. METHODS: Five patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 +/- 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated. RESULTS: The portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH(2)O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH(2)O to 258 mmH(2)O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl. CONCLUSIONS: We recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.     

胃左静脉腔静脉分流术治疗门静脉高压症八例

目的探讨胃左静脉腔静脉分流术治疗门静脉高压症的近期和远期疗效。方法对8例门静脉高压症患者施行胃左静脉腔静脉分流术 ,其中移植血管选用自体静脉 5例 ,人工血管 3例。结果本组无手术并发症及手术死亡 ,近期无再出血。随防 10个月至 10年 ,平均随访 5年 2个月 ,3例恢复轻体力劳动 ,2例恢复重体力劳动 ,2例死亡 ,1例失访。结论胃左静脉腔静脉分流术区域性降压效果好 ,兼有断流效果 ,对门静脉血流动力学干扰小 ,是一种安全理想的分流术式。     

Changes in humoral substances in induced cirrhosis and their effects on portal hemodynamics

The change of humoral substances in the blood of cirrhotic rat was studied at different stages of development, together with their effects on the portal hemodynamics. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models, as well as the changes of portal hemodynamics in the normal rats after perfusion with the arterial blood from cirrhotic rats were also investigated. It was found that: during the development of cirrhosis, glucagon increased markedly at all stages, histamine and vasoactive intestinal polypeptide (VIP) increased at early stage only, while serotonin (5-HT) and somatostatin(SS) increased at middle and advanced stages. In the CCl4 induced cirrhosis, glucagon was the main humoral substance, whereas in the thioacetamide (TAA) induced cirrhosis, histamine and 5-HT were mainly elevated. The portal hemodynamics altered differently in different stages during the development of cirrhosis and in the two different cirrhotic rat models. The perfusion with the arterial blood from cirrhotic rats caused an increase of portal venous pressure and portal venous flow in normal rats.     

Portal pseudoperfusion: an angiographic illusion.

Much confusion regarding the hemodynamics following interposition mesosystemic shunts prevails. Many authorities have claimed that portal venous perfusion continues following interposition mesocaval shunts. In 1971, a prospective, randomized trial comparing the distal splenorenal shunt with a variety of interposition mesosystemic shunts (primarily mesocaval or mesorenal) was begun. Visceral angiography was utilized to assess the early and late postoperative hemodynamic changes following both selective and nonselective shunts. None of the patients with patent interposition shunts retained portal perfusion present preoperatively. Searching for an explanation for this hemodynamic discrepancy, we examined two patients of the randomized trial angiographically. Both patients had excellent portal perfusion preoperatively, yet following interposition shunting (one mesocaval and one splenocaval), neither maintained portal perfusion of the liver. Celiac artery injections produced opacification of the entire splenoportal axis; however, it is shown that such portal venous opacification occurred in a retrograde direction by selective hepatic arterial injections demonstrating hepatofugal portal venous flow. Additionally, two nonrandomized patients received interposition mesorenal shunts and exemplify this phenomenon, entitled "portal pseudoperfusion". The explanation for conflicting literature reports lies in the misinterpretation of venous phase celiac and non-selective SMA arteriography in determining the direction of portal flow. A narrative of preoperative and postoperative angiograms of four patients will clarify the mechanism of "portal pseudoperfusion" and demonstrate that interposition shunts totally siphon portal venous perfusion. Clues to the detection and techniques to avoid this phenomenon will be presented.