Mesenteric venous hypertension: importance after portal systemic shunting?

Hepatic dysfunction after portacaval shunting (PCS) has been attributed to loss of portal perfusion to the liver. Proponents of selective systemic shunting state that reduced encephalopathy and hepatic dysfunction with this procedure result from the maintenance of portal perfusion to the liver through the hypertensive mesenteric venous circulation. We questioned the importance of maintaining the diminished portal flow to the cirrhotic liver because hepatofugal flow is known to develop in many of these patients. We sought to further define mechanisms that may contribute to the maintenance of critical flow to the liver in compensated hepatic cirrhosis. We demonstrated a primary relationship between mesenteric venous hypertension (MVH) and increased hepatic arterial blood flow after diversion of portal blood flow. Fifteen dogs had vena caval stenosis above an end-to-side PCS to establish MVH and deprive the liver of portal blood flow. Another 15 dogs had end-to-side PCS alone. A half hour after shunting, hepatic arterial blood flow had increased significantly in all dogs. Hemodynamic parameters remained stable throughout. Six weeks later, mesenteric pressure increased 98% +/- 3% with intracaval stenosis (from 9.6 +/- 0.1 to 19.0 +/- 0.3 cm H2O). Mesenteric pressure was unchanged with PCS alone (9.0 +/- 0.1 cm H2O). Increased hepatic arterial flow was significantly elevated in all dogs above pre-shunt values by 6 weeks postshunt. With MVH, however, further augmentation in hepatic arterial flow was noted in the chronic state (1.5 +/- 0.1 vs 0.9 +/- 0.1 ml/min/gm, p less than 0.05). There was significant correlation between MVH and increased hepatic arterial flow in the chronic state (r = 0.79, p = 0.05). Hepatic arterial flow 6 weeks after PCS with MVH was associated with lower blood ammonia and improved hepatocellular function compared with animals with PCS alone. These results support the hypothesis that MVH is important in maintaining blood supply--beyond providing driving force for sustained portal flow to the liver. This is an important consideration in the medical and surgical management of portal hypertension, a condition in which profound reduction in portal pressure may negatively affect compensatory hepatic arterial blood flow.     

Quantitation and fractionation of nutrient hepatic blood flow in normal persons, in persons with portal hypertensive cirrhosis, and after small-diameter portacaval H grafts

Patients maintaining portal perfusion following small-diameter portacaval H grafts have better survival and lower portasystemic encephalopathy rates than those with reversed flow. To determine why this is so, we measured nutrient hepatic blood flow with the use of 99m-Tc-diisopropyl-IDA (DISIDA) clearance pharmacokinetics fractionated into its hepatic arterial and portal venous components. Patients with cirrhosis and portal hypertension had significantly lower nutrient hepatic blood flow than normal persons; this was due almost entirely to reduced portal flow. In patients with prograde portal flow after small-diameter H grafts nutrient hepatic blood flows were nominally reduced from levels seen in patients with portal hypertensive cirrhosis. Postoperative patients with reversed portal flow had significantly less nutrient hepatic blood than those with prograde flow. There was no evidence of significant hepatic arterial compensation for lost portal flow. Of four hemodynamic variables--portal flow direction, portal flow, arterial flow, and nutrient hepatic blood flow--only nutrient hepatic blood flow showed an independent correlation with clinical outcome. Portal perfusion is a critical factor in maintenance of adequate nutrient hepatic blood flow, primarily because hepatic arterial flow does not compensate chronically for lost portal perfusion.     

'Cuffed' portacaval anastomosis in rat

Preparation of portacaval anastomosis (PCA) in patients suffering from portal hypertension has been an accepted procedure for reducing portal pressure. Recently, fashioning of mesocaval anastomosis has got preference. In the era of portacaval anastomoses numerous experimental works were concerned with the technique of performing them. During these experiments it was revealed that PCA produces considerable changes both in the metabolism and the circulation of the liver. Fischer et al. state that, following PCA, the weight of the liver decreased, on an average by 55%, as compared to the controls. Ossenberg et al. observed that after PCA liver perfusion was reduced by about 55-65%. Rubin et al. demonstrated that the hepatic cytochrome P 450 content was significantly decreased and the function of the microsomal drug metabolizing enzymes markedly altered subsequent to PCA. All these data indicated that, as a results of the bypassing of portal inflow from the liver, PCA significantly influences liver function and the intervention in experimental animals, i.e. rats, can be used as a model for chronic hepatic insufficiency.     

A casue of hepatic encephalopathy after portacaval shunt

The intestinal absorption of ammonia and D-xylose was studied under following conditions, i.e. Group 1: patent end-to-side portacaval shunts, Group 2: complete interruption of the portal vein, Group 3: constriction of the portal vein with minimal portal flow into the liver and Group 4: control. The concentration of ammonia and D-xylose in peripheral and portal blood was highest in group 1, but lowest in group 2. The two hour intestinal absorption rate of ammonium citrate and D-xylose was also highest in group 1 (80 per cent), but lowest in group 2 (40 per cent). Therefore, the reduced portal vein pressure after portacaval shunt seems to enhance intestinal absorption of cerebral toxins such as ammonia leading to hepatic encephalopathy after portacaval shunt in cirrhotic patients.     

Arterialization of the portal vein improves hepatic microcirculation and tissue oxygenation in experimental cirrhosis

BACKGROUND: Arterialization of the portal vein (APV) has shown beneficial effects on liver regeneration and function in selected patients undergoing liver resection and transplantation. Whether APV improves liver perfusion and function in cirrhosis is unclear. This study investigated the effect of APV on hepatic haemodynamics and liver function in a rat model of cirrhosis. METHODS: Male Sprague-Dawley rats (250-300 g) were divided into three groups: normal controls (n = 7), cirrhosis with sham laparotomy (sham; n = 7) and cirrhosis with APV (APV; n = 9). Portal venous blood flow, portal vein pressure and hepatic parenchymal microcirculation (HPM) were measured before and after APV. Hepatic parenchymal oxygenation was assessed by near-infrared spectroscopy and hepatocellular injury by standard liver function tests. Measurements were taken at baseline, after APV and 7 days after surgery. RESULTS: APV increased portal blood flow and pressure in cirrhotic rats without altering intrahepatic portal resistance. APV increased the HPM in cirrhotic rats by a mean(s.e.m.) of 28.5(0.1) per cent on day 0 and 54.6(0.1) per cent by day 7 (P = 0.001). Liver tissue oxygenation was increased by APV and the plasma gamma-glutamyltranspeptidase level was reduced (mean(s.e.m.) 6.0(0.5) versus 3.8(0.3) units/l before and after APV respectively; P = 0.006) at day 7. CONCLUSION: APV increases portal blood flow, tissue perfusion and oxygenation in cirrhosis.     

Liver arterialization prevents thrombocytopenia after portacaval shunt in rats

A low platelet count is a common finding in liver cirrhosis. Clinical practice has shown that a variable number of cirrhotic patients in whom portasystemic shunting procedures have been performed does not recover from thrombocytopenia: this observation questions the role that portal hypertension may have in maintaining the low platelet count. We have previously described the appearance of thrombocytopenia in rats submitted to portacaval shunt 1 month after the operation. In the present study we have investigated a supposed protective influence of a good liver function in maintaining a normal thrombocytopenia: 56 male Wistar rats were divided into 4 groups: group A (15 rats) sham-operated; group B (16 rats) submitted to portacaval shunt (PCS); group C (17 rats) submitted to PCS plus arterialization of the portal stump by the right renal artery, and group D (8 rats) submitted to PCS plus right nephrectomy. Group B (PCS) and D (PCS plus right nephrectomy) showed a marked thrombocytopenia, whereas group A (sham-operated) and C (PCS plus liver arterialization) evidenced a normal platelet count. These results strongly support the hypothesis that a low platelet count can ensue during a chronic liver disease in the absence of portal hypertension and that restoration of the hepatic blood flow can prevent thrombocytopenia.     

Haemodynamic and metabolic consequences of reversed portal venous blood flow after side-to-side portacaval shunt in the dog

The immediate haemodynamic and metabolic effects of reversed portal blood flow after side-to-side portacaval shunt were studied in 9 normal anaesthetized dogs, and compared to those observed after end-to-side shunt in the same animals. Blood flow in the hepatic artery (HA) and portal vein (PV) was measured using electromagnetic flowmeters. The magnitude of the HA hyperaemic response to side-to-side shunt was similar to that found after end-to-side shunt, but approximately one-third of the flow left the liver via the PV. There was no significant correlation between the HA response and the magnitude of reversed PV flow after side-to-side shunt. Despite fairly well preserved total hepatic oxygen consumption in both groups, there was a statistically significant decrease in the side-to-side series; moreover, only 13% of the total hepatic oxygen consumption was derived from blood draining the liver via the PV. It is concluded that the substantial quantity of portally drained blood after side-to-side shunt traverses metabolically inefficient pathways in the liver, and may have a detrimental influence on long-term liver function.     

抑制一氧化氮生物合成对门脉高压鼠血流动力学的影响

研究一氧化氮(NO)在门脉高压高血流动力学中的作用。方法:用SD大鼠制备肝内型(IHPH)、肝前型门脉高压(PHPH)和门腔分流(PCS)3组模型,并以正常鼠作为对照组。每一组实验动物再分成3个亚组:NO生物合成抑制剂L-NMMA组、L-NMMA NO生物合成底物L-精氨酸组以及生理盐水安慰组。血流动力学研究用放射性微球注射技术。结果:IHPH、PHPH和PCS鼠均具有心输出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等高血流动力学特征。L-NMMA能逆转门脉高压鼠和门腔分流鼠的高血流动力学状态,使之恢复至正常鼠的基础水平,但并未达到正常鼠用L-NMMA后的水平。如先给予L-精氨酸,则使L-NMMA对门脉高压鼠和门腔分流鼠的心血管作用消失。结论:门静脉高压症中NO过多产生是高动力循环重要的、但并不是唯一的介质。     

一氧化氮在门静脉高压症高动力循环中作用的实验研究

目的研究一氧化氮（ＮＯ）在门静脉高压症高血流动力学中的作用。方法用ＳＤ大鼠制备肝内型（ＩＨＰＨ）、肝前型门静脉高压（ＰＨＰＨ）和门腔分流（ＰＣＳ）三组模型,并以正常鼠作为对照组。每一组实验动物再分成三个亚组：ＮＯ生物合成抑制剂左旋单甲基精氨酸（Ｌ－ＮＭＭＡ）组、Ｌ－ＮＭＭＡ加ＮＯ生物合成底物Ｌ－精氨酸组以及生理盐水安慰组。血流动力学研究用放射性微球注射技术。结果ＩＨＰＨ、ＰＨＰＨ和ＰＣＳ鼠均具有心输出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等高血流动力学特征。Ｌ－ＮＭＭＡ能逆转门静脉高压鼠和门腔分流鼠的高血流动力学状态,使之恢复至正常鼠的基础水平,但并未达到正常鼠用Ｌ－ＮＭＭＡ后的水平。如先给予Ｌ－精氨酸,则使Ｌ－ＮＭＭＡ对门静脉高压鼠和门腔分流鼠的心血管作用消失。结论门静脉高压症中ＮＯ过多产生是高动力循环重要的、但并不是唯一的介质。     

Portal shunt operations. A critical observation on the selection of shunt methods]

In prehepatic block the method of operation is dependent on the anatomical and pathological condition of the blood vessels in the portal system. The choice of the shunt method has significant importance for the further progress of the disease and the social reintegration of the liver cirrhotic patients. Here, special attention should be given to possible postoperative hepatoportal encephalopathies. Portal hypertension is completely averted by direct portacaval anastomosis. It has a low risk but a relatively high incidence of postoperative encephalopathy. The lateral splenorenal shunt has a higher rate of recurrent bleeding but lower lethality, a higher long term survivalrate and a smaller number of encephalopathies. The coronariocaval anastomosis showed specially good results. This method is however only practicable in cases with extremely dilated coronaric ventricular veins. In the prevention of postoperative encephalopathies the central splenorenal anastomosis by Warren, Zeppa and Fomon has proved most effective. Modifications in method, especially the approach through the bursa omentalis and omission of the ligatur of the coronaric vein permits a significant decrease in the inherent surgical lethality. The pressure adapted arterialisation of the portal stump in portacaval shunt with iliacoportal bypass with saphenous vein interposition, as evolved by Matzander, seems to cause a significant decrease in the rate of postoperative encephalopathies after portacaval anastomosis. The prevention of postoperative encephalopathy is still the main problem of the technically perfected shunt operations. Solving this problem requires further investigation and research.     

Portal flow augmentation for liver cirrhosis

BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of death worldwide. Orthotopic liver transplantation offers the best therapeutic option but is available to only a minority of patients. In the past few years mechanically pumping portal venous inflow has been reported to reduce portal hypertension and improve liver function. METHODS: A review of the published data on augmented portal perfusion for the treatment of portal hypertension in cirrhosis was carried out by searching Medline and other online databases. From each published study portal pressure and blood flow data before and after augmented portal perfusion were used to calculate the change in mean intrahepatic portal vascular resistance (IHPR). The standardized data were then combined to allow meta-analysis. RESULTS: Seven papers were identified on normal and cirrhotic animal and human livers with augmented flow (50% to fourfold over baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous inflow was associated with a significant rise in portal venous pressure on the hepatic side (P < 0.001), a significant reduction on the mesenteric side (P < 0.001) and a significant reduction in IHPR (P = 0.013). Limited data were available to support improved liver function. CONCLUSION: Detailed in vivo cirrhotic liver studies on augmented portal flow in experimental models assessing haemodynamic and functional changes are required before clinical evaluation.     

门腔静脉侧仙分流加肝动脉强化灌注对肝硬变肝脏影响的实验研究

目的 门腔分流术严重影响肝脏血循环,为改善术后肝供血,设计并进行了门腔分流加肝动脉强化灌注术的实验研究。方法 ４８只Ｗｉｓｔａｒ大鼠被随机均分为：正常对照组（Ⅰ组）,肝硬变对照组（Ⅱ组）,肝硬变分流组（Ⅲ组）,肝硬变分流加肝动脉强化灌注组（Ⅳ组）;行肝功能检查,肝活检及核素动态肝胆显像。结果 Ⅳ组较Ⅲ组肝功能明显改善（Ｐ〈０．０５）。核素显像：高峰时间提前（Ｐ〈０．０５）;排泄率增高（Ｐ〈０．０１     

附加限制环的限制性门腔静脉侧侧分流加肝动脉强化灌注术的临床研究

目的 在实验研究证实其有效性的基础上，我们设计实施了附加限制环的限制性门腔侧侧分流加肝动脉强化灌注术的临床研究，以期改善门腔分流术后肝供血。方法 观察病例随机分为两组：附加限制环的限制性门腔侧侧分流加肝动脉强化灌注术组（简称：强化组）和附加限制环的限制性门腔侧侧分流术组（简称：分流组）；采用不同术式分别观察其术后近期效果。结果 强化组较分流组：术后近期，肝功能指标无明显改善；核素动态肝胆显像：通过强化肝动脉血流明显增加，因而对肝功能有一定的保护作用。结论 此术式通过强化肝动脉灌注，相对减少分流术造成的肝血供下降；相对增加肝营养因子的供给，对肝功能有一定维护作用，减轻术后肝纤维化程度；一定程度上克服了门腔分流术或断流术的不足，有望成为治疗门静脉高压症的新的实用术式。     

Effect of partial portal vein ligation on hepatic regeneration

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.     

Hepatic artery flow improvement after portacaval shunt: a single hemodynamic clinical correlate.

We have documented a highly significant increment in hepatic arterial flow following a portacaval shunt in patients with cirrhosis of the liver and portal hypertension. In contrast with other hemodynamic variables, the increment in arterial flow was directly related to morbidity, hospital mortality, and long term survival. Patients with increments smaller than 100 ml/min had the worst clinical results. They accounted for all of the hospital mortality, the largest incidence of encephalopathy, and the worst long term cumulative survival rates. The extent of the increment was not related directly to the type of shunt but, rather, to some intrinsic capability of the cirrhotic liver to increase its arterial flow in response to the relief of sinusoidal hypertension produced by the shunt. This capablilty appears related to the degree of entrapment of the hepatic arterioles by the fibrous tissues of cirrhosis. This encasement of arterioles should change the elastic properties of the hepatic arterial bed and we propose to measure these properties by determining the characteristic input impedance of the arterial bed.     

门脉高压大鼠胃粘膜屏障功能的实验研究

为探讨门脉高压性胃病的发病机理，将Ｗｉｓｔａｒ大鼠４２只随机分为肝硬变组（ＬＣ组，ｎ＝１５）、门静脉狭窄组（ＰＶＳ组，ｎ＝１５）和假手术组（ＳＯ组，ｎ＝１２），以观察其血流动力学指标、胃壁结合粘液（ＧＰ）、胃粘膜内源性前列腺素Ｅ２（ＰＧＥ２）水平、胃基础泌酸量（ＢＡＳ）以及Ｈ＋返渗量（Ｈ＋ＢＤ）。结果：ＬＣ组及ＰＶＳ组大鼠内脏血流量较ＳＯ组明显增加（Ｐ＜０．００１），但胃粘膜却处于缺血状态；其ＧＰ和ＰＧＥ２含量也较ＳＯ组显著下降（Ｐ＜０．０１），其中ＬＣ组又较ＰＶＳ组更低（Ｐ＜０．０５）；ＢＡＳ３组间无差异，但ＬＣ组及ＰＶＳ组大鼠之Ｈ＋ＢＤ明显高于ＳＯ组（Ｐ＜０．００１），且以ＬＣ组最为显著。本实验结果提示：门静脉高压大鼠胃粘膜屏障功能遭到严重破坏，尤以肝硬变大鼠为甚；门脉高压性胃病的发生与胃粘膜屏障功能削弱有关；肝功能受损参与胃粘膜病变的发生。     

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。     

Resectability and regeneration of liver in postsinusoidal block

To study resectability and regeneration of cirrhotic liver, hemodynamic changes following partial hepatectomy were observed in dogs with presinusoidal block caused by ligation of the portal vein or with postsinusoidal block caused by ligation of the hepatic veins after portacaval anastomosis, since cirrhosis of the liver in man is mainly of postsinusoidal block occasionally accompanied by presinusoidal block. With a presinusoidal block, resection of 50 per cent liver was tolerated well, but with postsinusoidal block only less than 30 per cent could be resected. Thus the functional reserve of the liver with postsinusoidal block seems to be much less than that of presinusoidal block. After major hepatic resection the weight of the remnant liver with a dual blood supply increased markedly, while with a postsinusoidal block it increased slightly and with a presinusoidal block there was no change. Histometric studies showed that regeneration was prominent in the remnant liver with a dual blood supply, slight with a postsinusoidal block, and even less with a presinusoidal block. Thus, the liver with a postsinusoidal block possesses more extensive regenerative capacity but shows much lower resectability than with a presinusoidal block. Therefore, the resectability of the liver associated with cirrhosis seems to be more closely related to its functional reserve capacity than to its regenerative capacity.     

Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole,Partial and DCD Grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.     

Significance of selective arteriographic patterns in the celiac axis and superior mesenteric artery in portal hypertension

Selective celiac and superior mesenteric arteriographies were performed in patients with portal hypertension. An arterioarterial (A-A) shunt between the superior mesenteric artery and the celiac axis via pancreatic arcades was found in fifteen of forty-three patients with associated massive splenomegaly. A mild A-A shunt disappeared after portacaval anastomosis alone, whereas a prominent A-A shunt was reduced but persisted. The persisting A-A shunt disappeared after splenectomy. These findings led us to suggest that the paucity of the blood flow in the common hepatic artery concomitant with increased splenic arterial flow to the massively enlarged spleen may result in a compensatory supply to the liver from the superior mesenteric artery via the shunt.