A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E₁ (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 g/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 g/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 g/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 g/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.     

The role of the abdominal sympathetic nervous system in regulating portal venous flow and its functional distribution

The role of the abdominal sympathetic nervous system in regulating portal venous flow (PVF) was examined in anesthetized rats using an ultrasonic volume flowmeter. Electrical stimulation of the hepatic sympathetic branch, given at 10 Hz, 1 ms, 10 s and 12 V, caused approximately a 28 per cent reduction in PVF, which was equivalent to that produced by occlusion of the bilateral carotid arteries for 30 s, without causing any change in the systemic arterial pressure. Stimulation of the major splanchnic nerve decreased PVF, the response being greater by stimulation of the right nerve than by stimulation of the left (p<0.05). Bilateral adrenalectomy shortened the recovery time without changing the magnitude or lateral predominancy. Neither proper hepatic arterial occlusion nor partial hepatectomy affected the response. In the partially hepatectomized animals, stimulation of the hepatic branch did not decrease the splenic flow but decreased the superior mesenteric venous flow (SMVF) and induced a similar response in PVF even when the SMVF was interrupted. An intraportal injection of noradrenaline decreased PVF dose-dependently. These findings indicate that the sympathetic nerve regulates PVF directly, and that there is functional laterality of the regulatory mechanism in the abdominal cavity, which suggests that adrenal factors work together with the nerve that supplies the portal vein.     

Omental delivery of prostaglandin E1 effectively increases portal venous blood flow in 66%-hepatectomized rats

Changes in portal venous blood flow (PVF) and systemic arterial blood pressure (SAP) were examined following prostaglandin E₁ (PGE) application to the greater omentum and femoral vein in 66%-hepatectomized rats. PVF increased when PGE was administered to the omentum and femoral vein at 7.5 μg/kg per min for 2 min. The magnitude of PVF response due to both administrations was dose-dependent, but the duration of the PVF response in the omental application was longer than that in the femoral administration. SAP was unchanged after omental application, while femoral administration reduced SAP concomitant with an increase in PVF. These results suggest that, in this hepatectomized model, the omentum is a better site for PGE administration than the vein, and that omental PGE delivery is also effective for enhancing PVF without inducing any changes in SAP.     

内皮素反义基因治疗门静脉高压症的研究

目的研究内皮素-1反义寡核苷酸（ET1-ASON）在内毒素（LPS）致门静脉高压中的作用.方法应用ET1-ASON预处理后将LPS以1 mg/kg体重腹腔注射大鼠,以正义、错义ET1-ASON和生理盐水作为对照,4 h后检测大鼠PVF、PVP、PVR和IVCP;应用放射免疫法、RT-PCR检测各组门静脉血和肝脏的ET1表达情况.结果ET1-ASON处理组大鼠门静脉血浆和肝脏组织ET1表达减低;PVR和PVP较对照组明显降低,PVF无明显改变.结论ET1-ASON在内毒素致门脉高压中主要通过降低PVR起作用.     

一氧化氮在大鼠肝硬变门静脉高压症形成中的作用及其对血液动力学 …

目的 探讨一氧化氮（ＮＯ）在肝硬变门静脉高压症（ＰＨＴ）形成过程中的作用。方法 采用比色法和鲎试验改良基质显色法,对大鼠肝硬变ＰＨＴ形成过程中,外周血ＮＯ、内毒素浓度和血液动力学的变化进行检测,观察了ＮＯ合成酶抑制剂Ｌ－ＮＭＭＡ对ＰＨＴ大鼠血液动力学的影响。 结果 （１）在大鼠肝硬变ＰＨＴ形成过程的早、中、晚三期,血浆ＮＯ和内毒素水平显著升高。（２）在肝硬变形成各期门静脉阻力（ＰＶＲ）和门静脉压力     

Intraoperative hemodynamic investigations during portacaval shunt

We studied the hemodynamics of hepatic blood flow before and after creation of portacaval shunts in 28 patients. Electromagnetic flow recordings were used to measure hepatic arterial flow (HAF) and portal venous flow (PVF) with respect to total hepatic blood flow (THBF). No correlation between PVF and portal pressure was found, but PVF was directly related to liver function. The concept that patients with low PVF tolerate shunts better (with respect to postoperative course and encephalopathy) than those with high PVF was not supported. Our investigations suggest the existence of a compensatory mechanism that tends to maintain THBF by increasing HAF following creation of a shunt. This compensatory increase occurs only in those patients with good liver function and normal or enlarged livers.     

肝缺血再灌注后肝内血流动力学的变化

目的探讨肝脏缺血再灌注（I／R）后肝内分流（IHSF）和功能性肝血流（FHBF）的变化。方法健康雄性SD大鼠l2只，作右侧颈动脉、颈静脉插管；开腹后，经回结肠静脉作门静脉插管，分别用以输血、输液、给药、留样、检测等。大鼠经部分肝I／R制模后，随机分为2组（每组6只）：（1）正常对照组（对照组），术中只分离肝周围韧带，不作肝门阻断及再灌注。（2）缺血再灌注组（1／R组，实验组），进行45min的肝门阻断及60min的再灌注。然后两组均经门静脉输注D一山梨醇（10mmol／L，0．2mL／min），2min后同时取颈动脉、门静脉、肝静脉血各1mL。测定门静脉血流量（PVF）、肝动脉血流量（HAF）。计算肝脏山梨醇摄取率、FHBF和IHSF。结果两组PVF，HAF及总肝血流量（THBF）无明显统计学差异；与对照组比较，I／R组肝脏山梨醇摄取率和FHBF减少，IHSF增加（P〈0．01）。结论肝I／R后，肝内血流动力学变化表现为肝内门一体分流开放，功能性肝血流减少。     

Arterialization of the portal blood with a new model of flow diversion: an experimental study

Arterialization of the portal blood with double shunts, cavo-mesenteric venous and femoro-femoral arterio-venous, was attempted in dogs. The experimental model was studied in three groups. Group-I was concerned with the condition immediately after establishment of the model. Group-II-A was referred to the study on the established model with hepatic artery ligation for seven days. Group-II-B was evaluated under hepatic artery ligation and absent participation in arterialization and shunts. The ratio of portal venous flow (PVF) to cardiac output (CO) in group-I revealed significant increase from 23 +/- 6% to 56 +/- 9% (p less than 0.01). Portal venous PO2 (PVO2) also increased from 48 +/- 7 mmHg to 65 +/- 9 mmHg (p less than 0.01). Portal venous pressure, however, remained below 200 mmH2O. Persistent increase of CO (150% of the control) and PVF/CO were seen in observation of group-II-A. Histopathological appearance of the liver was normal in group-II-A. Group-II-B revealed a high mortality rate (8/9) with necrosis of the liver by seventh postoperative day. The experimental model provides the useful flow diversion with arterialized blood to the portal flow. The arterialization of the portal flow may play an important role in the recovery of the ischemic liver cell in the preservation of the liver graft and in hepatic regeneration after extended resection.     

贲门周围血管离断术对门静脉血流动力学的影响

观察贲门周围血管离断术对门静脉血流动力学的影响,探讨手术与疗效的关系。方法:对22例门静脉高压病人行术前、后双功能多普勒超声检查和术中门静脉测压。结果:(1)术后门脉血流量(PVF)较术前减少18例,增加者4例。PVF的增减取决于胃冠状静脉侧支与脾静脉血流量的比值(CVF/SVF)。比值越小,术后PVF减少越显著;(2)术后肠系膜上静脉血流量增加;(3)门脉压力与PVF非同步变化,压力仍然维持较高水平。结论:上述血流动力学改变是临床上断流术后肝功能衰竭和脑病较少而远期再出血率较高的原因之一。     

The nonportal origin of the factors initiating hepatic regeneration.

To determine the site of origin of the factors that initiate deoxyribonucleic acid (DNA) synthesis in the liver after partial hepatectomy, normal rats were cross-circulated with totally hepatectomized rats. Half of the hepatectomized rats had also undergone excision of all of the portal organs. After 48 hours of cross-circulation, active DNA synthesis and other evidences of hepatic regeneration were found in normal rats cross-circulated with the hepatectomized portally eviscerated rats. This demonstrates that a blood-borne factor that does not arise from the portal organs is capable of initiating hepatic regeneration. When a normal rat was cross-circulated with a hepatectomized rat with the portal organs still present, hepatic regeneration occurred but was significantly less than when the portal organs had been removed. It is postulated that under these experimental conditions portal factors from the normal rat have a permissive role that allows active regeneration when initiating factors are furnished from the hepatectomized rat. Additional portal organs in the hepatectomized rat decreased DNA synthesis, possibly by alterations of the insulin/glucagon ratio.     

Correlation of portal venous velocity and portal venous flow with short-term graft regeneration in recipients of living donor liver transplants

BACKGROUND: To evaluate the correlation of postoperative portal venous velocity (PVV) and portal venous flow (PVF) with the degree of short-term graft regeneration in recipients of living donor liver transplantation (LDLT). MATERIALS AND METHODS: Between August 2005 and April 2006, we performed 44 adult-to-adult LDLTs with right-lobe grafts, of whom 31 recipients were included in this study. Doppler ultrasonography was used to measure PVV (cm/s) and PVF (mL/min) on postoperative days (POD) 1, 3, and 5 or 6. Portal venous velocity index (PVI) was defined as the ratio of PVV to graft weight (GW), and portal flow volume index (PFI) as the ratio of PVF to GW. Graft regeneration rate (GRR), defined as the ratio of the volume of regenerated graft to GW, was estimated by dividing computed tomography volumetry at POD 7 by GW measured after retrieval of the graft. We analyzed the relationship between GRR and PVV, PVF, PVI, and PFI. RESULTS: GW ranged between 528 g and 1040 g (mean = 735 g) and GRR ranged between 118% and 278% (mean = 172%). Although neither PVV nor PVF correlated with GRR, PVI and PFI at POD 1 (P = .009) and PFI at POD 5 or 6 (P = .012) significantly correlated with GRR at POD 7. CONCLUSION: PVI and PFI at POD 1 are useful indicators to predict short-term graft regeneration in recipients of LDLT.     

Optimal portal venous circulation for liver graft function after living-donor liver transplantation

BACKGROUND: Previous studies have shown poor outcome after living-donor liver transplantation (LDLT) as a result of excessive portal venous pressure (PVP), excessive portal venous flow (PVF), or inadequate PVF. We investigated optimal portal venous circulation for liver graft function after LDLT in adult recipients retrospectively. METHODS: Between June 2003 and November 2004, 28 adult patients underwent LDLT in our institution. We modulated PVP under 20 mmHg in these 28 cases by performing a splenectomy (n=4) or splenorenal shunt (n=1). The PVF and PVP were measured at the end of the operation. Compliance was calculated by dividing PVF by PVP. RESULTS: PVF and compliance showed a significant inverse correlation with peak billirubin levels after LDLT (r = -0.63: r=-0.60, P<0.01), and with peak international normalized ratio after LDLT (r=-0.41: r=-0.51, P<0.05). Compliance was higher in right-lobe graft with middle hepatic vein cases (148+/-27 ml/min/mmHg), and lower in left-lobe graft cases (119+/-50 ml/min/mmHg). CONCLUSIONS: Liver graft function was better when PVF and graft compliance were higher and PVP was maintained under 20 mmHg.     

CO2气腹对肝硬变大鼠门脉血流影响的实验研究

目的　探讨CO2 气腹对肝硬变大鼠门脉血流量的影响。　方法　制作肝硬变大鼠模型 ,施加不同压力的气腹 ,分别测平均动脉压、门静脉压力、下腔静脉压、门静脉血流 ,计算门静脉阻力。　结果　平均动脉压、下腔静脉压在不同气腹压力下无明显变化 ,两组大鼠门静脉压力在 10mmHg时出现显著差异 ,随着压力的升高而升高。正常大鼠的门静脉血流量在 2 0mmHg下与 0mmHg下比较有显著差异 ,而肝硬变大鼠的门静脉血流量在 10mmHg下与 0mmHg下比较已有显著差异。正常大鼠门静脉阻力随着压力的升高在 10mmHg时出现显著差异 ,以后继续升高 ,肝硬化大鼠门静脉阻力随着压力的升高持续升高。　结论　CO2 气腹致肝硬化大鼠门静脉血流减少 ,且减少程度重于正常大鼠     

Impact of a Left-Lobe Graft Without Modulation of Portal Flow in Adult-to-Adult Living Donor Liver Transplantation

In adult-to-adult living donor liver transplantation (LDLT), left-lobe grafts can sometimes be small-for-size. Although attempts have been made to prevent graft overperfusion through modulation of portal inflow, the optimal portal venous circulation for a liver graft is still unclear. Hepatic hemodynamics were analyzed with reference to graft function and outcome in 19 consecutive adult-to-adult LDLTs using left-lobe grafts without modulation of graft portal inflow. Overall mean graft volume (GV) was 398 g, which was equivalent to 37.8% of the recipient standard liver volume (SV). The GV/SV ratio was less than 40% in 13 of the 19 recipients. Overall mean recipient portal vein flow (PVF) was much higher than the left PVF in the donors. The mean portal contribution to the graft was markedly increased to 89%. Average daily volume of ascites revealed a significant correlation with portal vein pressure, and not with PVF. When PVP exceeds 25 mmHg after transplantation, modulation of portal inflow might be required in order to improve the early postoperative outcome. Although the study population was small and contained several patients suffering from tumors or metabolic disease, all 19 patients made good progress and the 1-year graft and patient survival rate were 100%. A GV/SV ratio of less than 40% or PVF of more than 260 mL/min/100 g graft weight does not contraindicate transplantation, nor is it necessarily associated with a poor outcome. Left-lobe graft LDLT is still an important treatment option for adult patients.     

Combined devascularization and proximal splenorenal shunt: is this a better option than either procedure alone?

Background/Purpose We aimed to determine the rationality of pericardial devascularization (PCDV) plus proximal splenorenal shunt (PSRS) for cirrhotic patients with portal hypertension with variceal bleeding, using a duplex sonography study of the effects of the different surgical procedures (PCDV, PSRS, and PCDV + PSRS) on the hemodynamics of the portal system.Methods Ninety-nine patients with cirrhotic portal hypertension and a history of bleeding esophageal varices were studied. These patients were divided into three groups (PSRS group, PCDV group, and PCDV + PSRS group). The hemodynamic parameters of the portal systems of all patients were measured by Doppler color-flow imaging perioperatively.Results In the PSRS group, the postoperative portal venous flow (PVF) and free portal pressure (FPP) decreased by 57 ± 9% and 52 ± 5%, respectively (P < 0.01). In the PCDV group, the postoperative PVF lessened by 8 ± 5% (P > 0.05), and the postoperative FPP was reduced by 19 ± 7% (P < 0.05). In the PCDV + PSRS group, the postoperative PVF and FPP were lowered by 36 ± 8% and 34 ± 10%, respectively (P < 0.05). The postoperative decreases of PVF and FPP in the PCDV + PSRS group were between those of the PSRS and PCDV groups. The differences among these groups were statistically significant (P < 0.05).Conclusions Combined devascularization and splenorenal shunt (PCDV + PSRS) significantly decreases portal venous flow and portal pressure, as well as maintaining hepatopedal flow, thus entailing fewer complications compared to either PCDV or PSRS.     

The Relationship between Portal Venous and Hepatic Arterial Blood Flow. I. Experimental Liver Transplantation

The relationship between the changes in portal venous and hepatic arterial blood flows, in the liver is a much disputed question, it has tremendous significance in the practice of transplantation, and an explanation has been available since 1981, when Lautt published the so-caled “adenosine washout theory”. According to our earlier observations the decrease of portal pressure or flow consistently led to an increase in hepatic artery flow. At the same time changes in hepatic artery flow or pressure seemed to produce only inconsistent effects on the portal circulation. In the present experiments liver transplantation (OLTX) was carried out on mongrel dogs by Starzl''s method. Electromagnetic flow probes were placed on the hepatic artery and the portal vein before removal of recipient’s liver, and after completion of all vascular anastomoses to the newly inserted liver, during the recirculatory phase of OLTX. The flow probes were connected to a Hellige electromagnetic flowmeter, portal venous and systemic arterial pressures were also recorded.The control HAF was 241±23 ml/min, the average PVF was 517±47 ml/min before removal of the recipients''s liver. In the recirculatory phase the HAF increased, by 71±12% (p < 0.001). The PVF decreased in most animals after OLTX. The decrease was in average –40.2±3.5% (p < 0.001). The THBF calculated by adding the HAF and PVF showed a small, but not significant decrease during recirculation.The systemic arterial pressure decreased slightly and portal vein pressure rose in most animals after OLTX. There was a substantial increase in portal inflow resistance and prehepatic arteriolar resistance and a decrease in hepatic artery resistance. The decrease of PVF after OLTX can be explained by progressive fluid accumulation in the liver parenchyma and increased sinusoidal and portal inflow resistance. The prolonged and continuous increase in hepatic artery flow during the recirculatory phase of OLTX may be due to the decrease of portal flow. The exact mechanism, by which a change in portal flow leads to arteriolar dilatation, can be most probably explained by the “adenosine washout theory” of Lautt.     

Improvement of morphological changes after 70% hepatectomy with portocaval shunt: preclinical study in porcine model

BACKGROUND: After extensive hepatectomy, excessive portal venous flow (PVF) and elevated portal venous pressure (PVP) may lead to postoperative liver damage. We have evaluated the use of portocaval shunt (PCS) to control PVF and PVP following partial hepatectomy (PH) to reduce the postoperative liver damage. METHOD: Twenty-four pigs were divided into two Groups: Group C (n = 10) underwent 70% PH alone and Group S (n = 14) underwent 70% PH with PCS. The changes in PVF, PVP, serum liver function tests, and histology were evaluated. RESULTS: PVP and PVF per unit of remnant liver weight and serum total bilirubin levels in Group S were significantly lower than those in Group C postoperatively (P < 0.05). Histology showed that there were significant differences in hepatocyte ballooning, necrosis, and neutrophil aggregation between the two groups (P < 0.05). In particular, hepatic necrosis was observed in zone 3 of Group C as centrilobular necrosis. These results suggest that hepatic and sinusoidal damage after 70% PH were more severe in Group C than in Group S, with the latter group maintaining an almost normal ultrastructural appearance. Hepatocyte apoptotic index differed significantly between the two groups (P < 0.0001). CONCLUSION: After 70% PH, extensive centrolobular necrosis and neutrophil aggregation were present and may have caused liver damage, manifested as hyperbilirubinemia and coagulopathy. The delayed liver regeneration with PCS may reduce the postoperative liver damages rather than the rapid liver hypertrophy. The diversion of PVF with PCS to maintain adequate PVP is a very effective procedure for avoiding the postoperative liver failure after extensive hepatectomy.     

The effects of intravenously infused catecholamines on hepatic blood flow in conscious dogs with experimental obstructive jaundice

This study was conducted to examine how the effects of dopamine and dobutamine on hepatic blood flow were influenced by obstructive jaundice in a conscious canine model. Prior to biliary obstruction, portal venous blood flow (PVF) increased in response to the infusion of either dopamine or dobutamine: dopamine infused at 8 g/kg per min produced an increase of 19±0% in PVF, while dobutamine infused at 16 g/kg per min produced an increase of 30±2%. Although hepatic arterial blood flow (HAF) decreased dose-dependently in response to the infusion of dopamine, no significant change was observed in HAF in response to any dose of dobutamine. Obstructive jaundice attenuated or completely abolished the PVF-increasing effect of dopamine, whereas it did not significantly alter the effect of dobutamine on hepatic blood flow. In dogs with obstructive jaundice, dopamine at 16 g/kg per min produced a decrease of 17±3% in PVF. These findings suggest that dobutamine is more effective than dopamine for increasing hepatic blood flow in patients with obstructive jaundice.     

Recovery of portal blood flow after percutaneous transhepatic biliary drainage in patients with obstructive jaundice

Using an ultrasonic Doppler system, we prospectively studied the changes in portal venous flow (PVF) following percutaneous transhepatic biliary drainage (PTBD) and evaluated the correlation between PVF and liver function in 10 patients with obstructive jaundice. The patients were divided into two groups according to their rate of decrease in serum bilirubin (“b”). Group A comprised 5 patients with a “b” of less than −0.1, while group B consisted of 5 patients who did not meet this criterion. The mean PVF increased following PTBD (P<0.01). The increase in PVF was due to an increase in the maximum velocity of the portal vein (Vmax). The rate of increase in the Vmax in group A was significantly higher than that in group B on both the 7th and 14th postdrainage days (P<0.05). The rate of increase in the Vmax correlated significantly with the rate of decrease in the serum bilirubin concentration (P<0.01). Based on the above findings, we conclude that measuring the Vmax by Doppler ultrasonography is useful in evaluating the liver function in patients with obstructive jaundice.     

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E₁ (PGE₁) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE₁ at 0.2 g/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE₁ was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE₁ is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.