Beneficial effects of arterialization of the portal vein on extended hepatectomy

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.     

肝切除时门静脉血部分动脉化的研究

目的 研究犬门静脉血部分动脉化的肝保护作用。方法 建立大保留肝（占全肝６０％）暂时性血流阻断、肝固有动脉切断并切除未阻断肝的急性肝衰模型（对照组）,并行肝总动脉与胃十二指肠静脉吻合（Ａ－Ｐ组）,观察生存率并定时测定丙氨酸转氨酶（ＡＬＴ）、动脉血酮体比（ＡＫＢＲ）及肝动脉脉、门静脉血气分析。结果 对照组７天生存率为３７．５％,Ａ－Ｐ组均较差异有非常显著性（Ｐ〈０．０１）,门静脉和肝静脉血氧分压均较术     

肝动脉阻断脾动静脉吻合对肝脏功能保护作用的研究

目的 观察肝动脉阻断后脾动静脉吻合的有效性和可行性。方法 将成年杂种犬分为肝动脉阻断组(HAL组)，肝动脉门静脉吻合组(PPAI组)，脾动静脉吻合组(PPA2组)，每组9只，观察术前、术后1h及4周时各项指标的变化。结果 HAL组术后门静脉压下降，肝静脉PO2下降、PCO2上升，门静脉GOT及GPT明显升高；PPAl，PPA2组术后门静脉压上升，P02及PCO2无明显变化，GOT及GPT术后1h明显升高，4周时恢复正常；PPAl，PPA2组与HAL组指标比较有极显著性差异(P＜0．01)，而PPAl组与PPA2组之间无明显差异(P＞0．1)。结论 脾动静脉吻合与肝动脉门静脉吻合等其它门静脉部分动脉化法一样对肝脏功能具有显著的保护作用，为普外科提供了一种手术方法。     

Tierexperimentelle Untersuchungen zur Arterialisierung der Pfortader bei der Lebertransplantation am Göttinger Miniaturschwein

The aim of the present experimental investigation was to assess the circulatory, biochemical and histopathological consequences of complete portal vein arterialization of the transplanted liver in ‘Göttinger’ miniature pigs. Orthotopic liver transplantations using a passive portojugular shunt were performed in six male ‘Göttinger’ miniature pigs. Using an iliac artery segment interposition of the animal donor, the hepatic artery (HA) of the transplant liver was anastomized end-to-end and the portal vein (PA) also united with the internal iliac artery stump end-to-end. The central anastomosis was performed onto the suprarenal aorta. Portal vein blood was drained into the infrahepatic caval vein via an end-to-side shunt (PCS). During the course, the following parameters were determined: arterial blood pressure, venous pressure, cardiac output, electromagnetic blood flow measurements across the HA, PA, and PCS, PA mean pressure, transaminases, partial thromboplastin time and fibrinogen. Liver biopsies and autopsy specimens were investigated. One of six animals died a few hours postoperatively, two of six died after 48 and 72 h, respectively, whereas three pigs survived the scheduled 7 days. The cardiac output fell intraoperatively initially by an average of 20 % but had approximately the starting volume of 2.2 l/min at the end of the operation. Although the diameter of the anastomosis was reduced to 4 mm, the flow in the arterialized PA on average was 340 ml/min when the vessel clamp was opened. At the end of operation the mean was 380 ml/min, the interval of measurement being 75 min. The flow across the PCS and the HA were constant during the course. As mechanism for this phenomenon, autoregulation of the liver blood flow on a sinusidal level has been suggested. The biochemical results and the histopathological findings showed no change compared to previous findings in a control group of animals in which liver transplantion was performed by our team. Complete arterialization of the PA is well tolerated in liver transplantation in ‘Göttinger’ miniature pigs with regard to circulation and liver function in a short-term trial of a maximum of 7 days. Long-term results are still to come.     

Effect of inspired oxygen on portal and hepatic oxygenation: effective arterialization of portal blood by hyperoxia

Because hypoxia may compromise the survival of intraportally transplanted pancreatic islets, we have measured portal blood flow and both portal and hepatic oxygenation in normal and diabetic rats breathing graded inspired oxygen concentrations. Portal blood flow and hepatic tissue oxygenation were measured using a transonic flowmeter and near infrared spectroscopy while gas analysis was carried out on portal venous blood samples. The effects of breathing 13%, 21%, 50%, or 100% oxygen were compared in animals with steptozotocin-induced diabetes and in controls. In diabetic rats breathing 21% oxygen, portal blood flow was significantly lower than in controls (7.2+/-0.7 vs. 9.1+/-0.8 ml/min, p < 0.05). In both groups, breathing 100% oxygen significantly increased portal flow (to 8.4+/-1.0 and 12.2+/-0.7 ml/min, respectively). This effect was not secondary to hepatic arterial vasoconstriction because it was not prevented by hepatic artery ligation. In controls, breathing 100% oxygen increased portal pO2 from 5.0+/-0.9 to 14.4+/-1.4 kPa (p < 0.05) and portal venous oxygen saturation (PSaO2) from 53.9+/-12.1% to 92.9+/-1.4% (p < 0.05), a value not significantly different from peripheral (arterial) saturation. Similarly, in diabetic animals pO2 rose from 5.6+/-0.3 to 11.7+/-0.4 kPa (p < 0.01) and SO2 from 55.5+/-5.2% to 88.5+/-0.6% (p < 0.05). Hepatic oxyhemoglobin rose and deoxyhemoglobin fell reciprocally as a function of the inspired oxygen concentration. Improved hepatic oxygenation observed in animals breathing oxygen-enriched gas mixtures results from an increase in splanchnic blood flow coupled with a marked increase in portal oxygen saturation. This effective arterialization of portal blood may have important consequences for the success of intraportal transplantation of pancreatic islets.     

Liver circulation and oxygen metabolism during short time ligation and the hepatic artery in the dog

The changes of liver circulation and liver oxygen metabolism during and after one hour hepatic artery ligation (HAL) were studied in eight mongrel dogs. At the end of the HAL period total hepatic blood flow (THBF) was reduced from 115.6 +/- 5.5 ml/min . 100 g liver tissue to 68.0 +/- 3.7 ml/min . 100 g or 59% of the initial value. The portal venous blood flow was reduced from 83.1 +/- 3.4 to 58.8 +/- 3.7 ml/min . 100 or 82% of the initial value and the liver oxygen consumption was reduced from 4.1 +/- 0.2 ml/min . 100 g to 3.1 +/- 0.3 ml/min . 100 g or 76% of the initial value. The changes in portal venous blood flow and liver oxygen consumption were reversible following reopening of the hepatic artery. The clinical importance of a reduced portal venous blood flow and liver oxygen consumption following HAL and the possibilities to increase the portal venous blood flow are discussed.     

The measurement of hepatic circulation before and after orthotopic liver transplantation in dog--by using transit-time blood flow meter and H2 clearance method

Orthotopic liver transplantation was successfully carried out in 40 mongrel dogs, in which hepatic circulation was investigated before and after grafting. Blood flows in hepatic artery, portal vein and intrahepatic inferior vena cava were measured by using transit-time ultrasonic blood flow meter and regional tissue blood flow was determined by hydrogen gas clearance method. Before transplantation the mean blood flows were 234 +/- 95mg/min in portal vein, 118 +/- 76ml/min in hepatic artery and 291 +/- 103ml/min in inferior vena cava in 40 recipients. The blood flow ratio of portal vein and hepatic artery was 2.9 +/- 2.2. The mean regional blood flow of the liver was 63 +/- 24ml/min/100g. After transplantation, the mean blood flows decreased to 189 +/- 86ml/min in portal vein, 77 +/- 51ml/min in hepatic artery and 179 +/- 111ml/min in inferior vena cava and the regional tissue blood flow was 57 +/- 25ml/min/100g. Hepatic arterial flow decreased by 37 percent after transplantation, however, portal venous flow decreased by 24 percent and the regional blood flow decreased by 9 percent after transplantation of the liver. These data suggested that the microcirculation of the liver was slightly disturbed after liver transplantation in dog, which was in part due to the decreased blood flows of the hepatic artery and portal vein.     

Study on splanchnic circulation: measurement of the liver blood flow

In anesthetized patients during abdominal surgery, hepatic artery and portal vein flows were measured simultaneously utilizing an ultrasonic transit-time volume flowmeter. The total hepatic blood flow was 994.6 +/- 52.4 ml/min. The hepatic artery flow and the portal vein flow were 260.0 +/- 23.8 ml/min and 730.8 +/- 41.3 ml/min, respectively. The ratio of hepatic artery flow to portal vein flow was 0.37 +/- 0.04. A significant increase in hepatic artery flow (p less than 0.01) followed portal vein occlusion, whereas no significant change was observed in portal vein flow after hepatic artery occlusion. Common hepatic artery occlusion resulted in a significant decrease in hepatic artery flow (p less than 0.05), but no significant change was observed in portal vein flow. The present study firstly demonstrated that ultrasonic transit-time volume flowmeter is a device to quantitatively assess hepatic artery and portal vein flows with good reproducibility and stability in human subjects. This easy and simple technique seemed to have wide clinical application to abdominal surgery and would have a promising in studying splanchnic blood flows in various situations such as in cases of hepatectomy and portal hypertension.     

Washout of the pig liver with Haemaccel after hypothermic preservation

In hepatic preservation by simple perfusion and hypothermic storage, a portal and hepatic washout before revascularization would avoid receptor hyperkaliema. In this report we study the effectiveness of this washout with Haemaccel at room temperature. Large-White pigs were used and eight livers were perfused "in situ" via the portal wein with Hartmann's solution containing 10,000 IU of heparin at 4 degrees C, and afterwards, via portal and arterial routes with C2 solution at 4 degrees C. After a cold ischemia time of less than 31/2 hours a liver washout via the portal vein and hepatic artery with Haemaccel before portal revascularization was done. The high concentrations of glucose, K+, GOT, GPT and LDH in the effluents obtained during the washout are attributed to Haemaccel hyperosmolarity. A portal and arterial hepatic washout associated with free drainage of the first 50-100 ml of portal venous blood after hepatic portal revascularization through the infrahepatic inferior vena cava (IH-IVC), prevents hyperkaliemia from occurring after a portal and arterial revascularization in the orthotopic liver transplant (OLT) in pigs.     

Evaluation of temporary portal vein arterialization: the minimum arterialized blood flow for maintaining liver viability

Abstract. The effect of temporary portal vein arterialization (PVA) on hepatic energy metabolism was investigated by changes in the arterial blood ketone body ratio (KBR) and hepatic energy charge (EC) level in 17 dogs. The KBR decreased markedly after clamping the hepatic hilar vessels combining mesocaval shunt and remained at a low level throughout hepatic ischemia. After PVA, the KBR was rapidly restored and maintained at sufficient levels. EC at 60 min after arterialization also recovered to the preclamping level. By reducing the arterial shunt flow, the critical point of arterialized blood flow for maintaining the KBR at high levels was assessed to be about 10% of the total hepatic blood flow (THBF). These findings demonstrate that temporary PVA is an effective method for maintaining the functional capacity of the liver, and that the minimum arterialized blood flow needed to preserve liver viability is only about 10% of the total hepatic blood flow.     

Evaluation of temporary portal vein arterialization: the minimum arterialized blood flow for maintaining liver viability

The effect of temporary portal vein arterialization (PVA) on hepatic energy metabolism was investigated by changes in the arterial blood ketone body ratio (KBR) and hepatic energy charge (EC) level in 17 dogs. The KBR decreased markedly after clamping the hepatic hilar vessels combining mesocaval shunt and remained at a low level throughout hepatic ischemia. After PVA, the KBR was rapidly restored and maintained at sufficient levels. EC at 60 min after arterialization also recovered to the preclamping level. By reducing the arterial shunt flow, the critical point of arterialized blood flow for maintaining the KBR at high levels was assessed to be about 10% of the total hepatic blood flow (THBF). These findings demonstrate that temporary PVA is an effective method for maintaining the functional capacity of the liver, and that the minimum arterialized blood flow needed to preserve liver viability is only about 10% of the total hepatic blood flow.     

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.     

Temporary portal vein arterialization as an attractive option in canine orthotopic partial liver transplantation.

We performed 22 canine orthotopic partial liver transplantations (PLTs) with three different revascularization methods; portal vein arterialization (PVA group, n = 11), hepatic arterial shunt (HAS group, n = 5), and conventional portal vein reperfusion (control group, n = 6). Our purpose was to evaluate the feasibility of PVA as a revascularization technique in PLT assessing the changes in arterial ketone body ratio (KBR) as an index of hepatic energy status. After the first anastomosis (left hepatic vein), the ischemic partial liver graft was revascularized with arterial blood flow shunted from the external iliac artery to the hepatic side of the portal vein (PVA group) or the proper hepatic artery (HAS group). Both anhepatic period and ischemia time were significantly shortened in groups PVA and HAS as compared with those in control. In the PVA group, 10 out of 11 recipients survived for at least 5 days (14.2 +/- 3.8 days, mean +/- SEM), while 3 out of 5 (5.2 +/- 1.0) survived in the HAS group and 4 out of 6 (6.2 +/- 1.3) in the controls. Although portal blood flow during PVA was only about 25% of the total hepatic blood flow at preclamping, the KBR was rapidly restored after PVA and showed almost the same values at preclamping. The KBR values during the arterialization time and initial velocity of KBR recovery in the PVA group were significantly higher than those in the HAS and control groups. These results suggest that PVA presents an attractive option in PLT.     

限制流量的门静脉动脉化对大鼠肝脏功能和结构的远期影响

目的 探讨限制流量的门静脉动脉化术后门静脉血液动力学改变，以及对肝脏功能和结构的远期影响。方法 建立大鼠门静脉完全动脉化（portal vein arterialization，PVA）以及限制流量的大鼠门静脉动脉化模型，观察术后1及6个月门静脉血流量、横截面积以及术后6个月门静脉压力及肝脏结构和功能的变化。结果 末采取限制流量措施的门静脉动脉化术后门静脉横截面积和血流量随时间延长呈增加的趋势，术后6个月血清ALT水平显著升高（F=7，72，P〈0，01）。肝内门静脉及其分支显著增宽、壁增厚、内膜胶原纤维增多。而限制流量的门静脉动脉化术后门静脉横截面积与血流量增加趋势不显著，血清GPT水平接近正常水平，术后6个月，3组大鼠动脉化门静脉压力、血浆内毒素、动脉血酮体比值以及血清白蛋白、总胆红素和碱性磷酸酶水平差异无统计学意义。结论 门静脉完全动脉化后，限制流量是必要的，保持一定流量的动脉化门静脉血，对于维持肝脏正常生理功能，防止过高血流量对肝脏功能和结构的损害，有重要意义。     

Comparative study of artifical circulation for the liver after cardiogenic shock: Pulsatile or nonpulsatile?

Because of multiple organ failure (MOF), the survival rate of patients with mechanical circulatery support has not been satisfactory, The purpose of this study is to estimate the effects of pulsatile and nonpulsatile artificial circulation on hepatic microcirculation and function. Cardiogenic shock was induced experimentally by ligating of left anterior descending branch in pigs. For the right ventricular assist device, a nonpulsatile pump (Nikkiso HPM-15) was employed. The left ventricular function was supported by either a nonpulsatile pump (Nikkiso HPM-15: NP group) or a pulsatile pump (Zeon Medical: P group). NP group was further devided into 80% support (NP-1 group) and 100% support (NP-2 group) of the control cardiac output. All groups were maintained at an equivalent mean aortic presure of 3 hours. We measured the hepatic artery blood flow, portal vein flow and hepatic regional blood flow. For the metabolic and hepatic oxygen metabolic data, GOT, GPT, arterial blood ketone body ratio (AKBR), lactate/pirubic acid (L/P), and hyaluronic acid were evaluated. The mean aortic pressure was higher in the NP-2 group than in the other grousp. The hepatic arterial blood flow was significantly higher in the P group than in the others. The AKBR and hepatic oxygen metabolism showed significant improvement in the P group in comparison with others. The regional blood flow in the liver showed improvements in the P and NP-2 groups. These findings suggested that pulsatile circulation may be beneficial for microcirculation of the liver; and the augmented nonpulsatile flow had effects similler to those of pulsatile flow in hepatic circulation.     

Improved microcirculation of a liver graft by controlled portal vein arterialization

BACKGROUND: The clinical results of portal vein arterialization (PVA) in liver transplantation are controversial without a standardized portal flow regulation. The aim of these experiments was to perform a flow-regulated PVA in liver transplantation, to examine the microcirculation and early graft function after heterotopic auxiliary liver transplantation (HALT) with flow-regulated PVA, and to compare this technique with HALT with porto-portal anastomosis. Using the recently developed orthogonal polarization spectral (OPS) imaging, for the first time the microcirculation of liver grafts with PVA was visualized. MATERIALS AND METHODS: HALT was performed in Lewis rats. The portal vein was either completely arterialized via the right renal artery in a standardized splint-technique (Group I, n = 8) or anastomosed end-to-end to the recipient's portal vein (Group II, n = 8). RESULTS: After reperfusion, the average blood flow in the portal vein was within the normal range in Group I (1.7 +/- 0.4 ml/min/g liver weight) and significantly higher than in Group II (1.2 +/- 0.2 ml/min/g liver weight). The functional sinusoidal density in Group I (335 +/- 48/microm) was significantly higher than in Group II (232 +/- 58/microm), whereas the diameter of the sinusoids and the postsinusoidal venules yielded no significant differences between both groups. The bile production was comparable (27 +/- 8 versus 29 +/- 11 microl/h/g liver weight). CONCLUSIONS: In our experiments it was possible to achieve an adequate flow regulation in the arterialized portal vein with good results concerning microcirculation and early graft function. We recommend that further investigations on liver transplantation with PVA should be performed with portal flow regulation, before PVA is employed in clinical transplantation.     

门静脉部分动脉化对大鼠肝部分切除后肝脏的影响

目的探讨门静脉部分动脉化对部分肝切除大鼠肝脏的影响。方法将48只SD大鼠分为肝部分切除术后非门静脉动脉化组及门静脉动脉化组。动态观察术后2，6，12h血清ALT，AST，以及肝组织中ATP，ADP，AMP含量的变化，并计算EC值；同时取肝组织行病理组织学检查。结果（1）与非动脉化组比较，动脉化组血清AST和ALT在术后2h无差异（P〉0．05），术后l2h动脉化组血清AST和ALT动脉化组明显降低（分别为P〈0.01及P〈0.05）。（2）动脉化组较非动脉化组术后各时点肝组织ATP和Ec均有明显增加（分别为P〈0.01及P〈0．05）。（3）非动脉化组肝组织病理变化随着缺血时间延长而加重；动脉化组病理变化较轻。结论门静脉部分动脉化在一定程度上可以减轻大鼠部分肝切除并肝动脉离断后的肝损害，改善肝细胞的能量代谢。     

The experimental study on the temporary portal vein arterialization in the canine liver transplantation: preliminary report

To evaluate the feasibility of temporary portal vein arterialization (PVA) in orthotopic partial liver transplantation (PLT), we performed 5 canine PLTs with PVA assessing the changes in arterial ketone body ratio (AKBR) as an index of hepatic energy status, and measuring portal pressure and flow. After anastomosis of hepatic vein, the graft liver was revascularized with arterial blood shunted from the external iliac artery to the hepatic side of the portal vein. By using this technique, both anhepatic period of the recipient and ischemic time, especially warm ischemic time, of the allograft were markedly shortened (31.0 +/- 4.5 min: Mean +/- SEM). Four out of 5 recipients survived for at least 5 days (13 days in average). The AKBR was restored immediately after PVA and showed almost the same values as those at preclamping and after completion of anastomoses of both portal vein and hepatic artery. No significant difference in portal venous pressure was observed between during PVA and after vascular reconstruction. Portal blood flow during PVA was about one fourth of the total hepatic blood flow at preclamping. These results suggest that PVA can be used as an alternative procedure in PLT.     

缝扎肝右静脉后肝动脉与门静脉血流改变的实验研究

目的：探讨结扎主肝静脉对肝动脉与门静脉血流动力学的影响。方法：小型猪共12头，剖腹后，电磁血流计测量结扎前后肝动脉、门静脉血流，大网膜静脉置管测量结扎前及结扎后30min、1、3、5、7、14、21、28、56d的自由门静脉压力(FPP)，56d后再次开腹测量肝动脉、门静脉血流。结果：FPP术后均升高，以术后7d内明显，6头超过35cmH2O，且其中3头小猪出现上消化道出血；肝动脉血流速早期增加，56d降至略高于术前水平；门静脉血流速早期减少，未检测到逆向血流，术后56d，门静脉血流速恢复为略低于术前水平。结论：结扎一条主肝静脉不会引起结扎肝叶的萎缩坏死，可能会导致上消化道出血。     

Hemodynamic Changes in Blood Flow Through the Denervated Liver in Pigs

We investigated the effects of liver denervation on hemodynamic circulation in seven anesthetized pigs. Simultaneous measurements of the hepatic artery and portal vein were performed with an ultrasound Doppler flow meter before and after liver denervation. Neither resting systemic nor hepatic hemodynamics changed following liver denervation. However, temporary occlusion of the portal vein resulted in a significant increase in hepatic artery flow in the innervated liver (from 123 ± 15 ml/min to 177 ± 17 mu/min, p <. 01), whereas, in the denervated liver, a significant decrease was observed (from 128 ± 11 ml/min to 106 ± 19 mu/min. p >. 05). Thus, the reciprocity between the hepatic artery and portal vein in the innervated liver disappeared in the denervated liver. The absence of an increase in the hepatic artery flow during portal vein occlusion might intensify symptoms of portal vein thrombosis in liver transplantation. In the denervated liver, a significant decrease also occurred in systolic blood pressure and central venous pressure from 1 to 3 min after portal vein occlusion. Since the liver plays a crucial role in the maintenance of cardiovascular homeostasis during blood loss, it is likely that denervation at the porta hepatis induced a lack of vasoconstriction in the portal territory. Liver denervation might further exacerbate this response to hypotension. The current study confirms that the hepatic nerves play an important role in hepatic arterial and portal venous interactions aimed at maintaining a constant blood flow through the liver. We also suggest that the hepatic nerves are important for cardiovascular homeostasis.