Xanthine oxidoreductase and preservation injury in human liver transplantation

BACKGROUND: Preservation injury is a major cause of primary graft dysfunction in liver transplantation (LT). Oxidative damage is considered to be the first event leading to graft damage. Xanthine oxidoreductase (XOR) and neutrophil activation, two sources of reactive oxygen species, could play a role in the development of graft dysfunction. METHODS: We determined activities of XOR forms, polymorphonuclear elastase (PMN-E), aminotransferases, and hyaluronic acid in plasma of 20 patients undergoing LT. Samples were taken from the radial artery (RA) before the anhepatic phase; from the portal vein (PV) before reperfusion; from graft caval effluent (CE) at reperfusion; and from RA, PV, and the hepatic vein (HV) 10 and 90 min postreperfusion. RESULTS: The graft, but not recipient bowel, released XOR into blood (XOR in CE, median, 61.2 mU/g protein [range, 1.9-160.4 vs. undetectable in PV before reperfusion). Circulating XOR was transformed from dehydrogenase to reversible oxidase (XOrev) (XOrev-to-XOR ratio, 48.1% in CE and 65.1% in HV 90 min postreperfusion). Neutrophil activation was detected in the recipients before reperfusion, and in liver at early post-reperfusion (median PMN-E was 0.85 microg/g protein [range, 0.01-1.58] in RA before the anhepatic phase; 2.22 microg/g protein [range, 0.20-5.88] in PV prereperfu-sion; and 3.60 microg/g protein [range, 0.48-6.78] in HV 10 min postreperfusion). XOR, but none of the other markers, was higher in the CE of patients with moderate primary graft dysfunction than in those with slight primary graft dysfunction. CONCLUSIONS: XOR release and neutrophil activation are produced during LT, and they are potentially injurious mechanisms associated with this therapy.     

入肝门静脉动脉化加门腔分流术对肝硬化大鼠血流动力学的影响

目的对肝硬化大鼠利用右肾动脉行入肝门静脉动脉化+门腔分流术,研究该术式对肝硬化大鼠门静脉血流动力学的影响。方法四氯化碳(CCl4)诱导肝硬化大鼠成模后,分为A组(动脉化组)15只,利用右肾动脉行门静脉动脉化+门腔分流术,B组(对照组)10只,单纯行右肾切除及门静脉阻断10min后关腹。术后即刻、术后1月和术后3月分别检测门静脉压力、内径和血流量。结果术后即刻、术后1月和术后3月A组大鼠与B组相比,入肝门静脉压力和入肝血流量明显升高,随时间推移入肝门静脉压力有下降趋势,但仍高于对照组(P0.01),而入肝血流量则持续增加,明显高于对照组(P0.01)。入下腔静脉门静脉压力则明显下降并维持在较低压力水平(P0.01)。术后A组入肝门静脉内径较B组门静脉内径明显增宽(P0.01),但术后1月至3月入肝门静脉在适应压力变化后,内径趋稳在一定水平。结论门腔分流术对肝硬化大鼠可以有效降低门静脉循环压力,减少静脉曲张出血的危险性;进一步行入肝门静脉动脉化则可有效增加入肝血流量,入肝门静脉压力及血流量随时间推Σ可在较高水平取得新的平衡。     

Role of NF-kappaB as effector of IPC in donor livers before liver transplantation in rats

The objective of this study was to investigate the effect of ischemic preconditioning (IPC) on NF-kappaB activity during reperfusion early after liver transplantation in rats. METHODS: Male Sprague-Dawley (SD) rats were used as donors and recipients of orthotopic liver transplantations. The donor liver was stored 2 hours in Ringer's solution at 4 degrees C preimplantation. IPC was performed by clamping of the portal vein and hepatic artery of the donor for 10 minutes followed by reperfusion for 10 minutes before harvesting. At 1, 2, 4, and 6 hours after portal vein reperfusion, graft samples were obtained to determine hepatic levels of NF-kappaB activity, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule (ICAM)-1. Blood samples were obtained to measure serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). RESULTS: After liver transplantation without IPC, serum levels of ALT and LDH increased significantly compared with the sham-operated group. Among the IPC group, serum ALT and LDH decreased significantly. NF-kappaB activity in the graft increased within 6 hours after transplantation. Among the IPC group, NF-kappaB activity was significantly attenuated. Hepatic levels of TNF-alpha and ICAM-1 were significantly elevated in the non-IP group but both were reduced in the IPC group. CONCLUSION: IPC downregulated TNF-alpha and ICAM-1 expression in the graft, most likely through decreased NF-kappaB activation, and attenuated neutrophil infiltration after reperfusion.     

去除门静脉淤血减轻肝脏缺血再灌注损伤的实验研究

目的 探讨去除门静脉淤血对肝脏缺血再灌注损伤的影响及机制.方法 检测家兔肝脏原位冷灌注20、30、40 min后淤血的门静脉中内毒素含量变化,观察门静脉淤血去除对恢复灌流后4 h血清内毒素、丙氨酸转氨酶(ALT)、透明质酸(HA)、肝组织匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)及肝组织核因子-κB(NF-κB)活性的影响.结果 门静脉淤血中内毒素含量随阻断时间延长明显升高(P＜0.01),同一阻断时间每去除2.5 ml淤血血清内毒素含量显著下降(P＜0.01).在阻断30 min和40 min组,去除门静脉淤血能降低血清ALT、HA、及肝组织匀浆MDA的含量和肝组织NF-κB活性,增加肝组织匀浆SOD活性,与不去除相比较差异有统计学意义(P＜0.05).在阻断20 min组去除门静脉淤血与不去除相比较,各检测指标差异无统计学意义(P＞0.05).结论 门静脉淤血中内毒素含量随阻断时间延长明显升高,可能是引起肝脏损伤的主要原因;去除门静脉淤血可以减轻肝脏的再灌注损伤,其机制可能与门静脉淤血去除减少内毒素吸收,进而降低肝组织NF-κB活化有关.     

Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation.

BACKGROUND: During orthotopic liver transplantation (OLT), it is standard procedure to reperfuse the liver via the portal vein (PV) despite having a lower oxygen content and perfusion pressure than the hepatic artery (HA). There are no published studies that describe graft function and outcome when the HA is used for reperfusion. We report a retrospective comparison of graft outcome after HA or PV reperfusion when the piggyback technique was used. METHODS: We identified 26 patients who had undergone OLT with HA reperfusion and 26 patients reperfused via the PV. Demographics, primary diagnosis, surgeon, warm and cold ischemic times, and blood product use were recorded. In each patient, whole blood lactate concentration, prothrombin time (PT), and alanine aminotransferase (ALT) were measured at defined time points during and after surgery as indices of graft lactate metabolism, synthetic function, and reperfusion injury, respectively. Thirty-day and 1-year outcome data were recorded. Data were compared between the HA and PV groups. RESULTS: Demographics, blood product use, primary diagnosis, cold ischemic time, and surgeon were similar between the groups. Warm ischemic time was longer in the HA group (mean [SD] HA 51.2 [14.7], PV 40 [9.1] min, P=0.002). Blood lactate concentrations were similar at all time points. There was no difference in 24-hr postoperative PT between the groups (median [InterQuartile (IQ) range] HA 17.5 [16-28.3], PV 19 [16-24] sec, P=0.85). Peak postoperative ALT values were comparable (median [IQ range] HA 1031 [668-1701], PV 1107 [754-1824] IU/ml, P=0.78). There were no statistically significant differences in 30-day or 1-year mortality, but more early deaths occurred in the HA group. Using our data, we calculated that a prospective randomized trial would need approximately 300 patients to be sure that mortality was the same with both techniques. CONCLUSION: We have demonstrated no clinically or statistically significant differences in indices of graft function, reperfusion injury, or outcome between primary HA or PV reperfusion.     

Hepatic arterial buffer response after pediatric living donor liver transplantation: report of a case

Background

Excessive portal pressure at an early stage after living-donor liver transplantation (LDLT) can damage sinusoidal endothelial cells and hepatocytes through shear stress leading to graft failure, or hepatic arterial complications due to low hepatic artery flow from a hepatic arterial buffer response. We encountered a case in which excessive portal vein flow was observed from an early stage after pediatric LDLT. The hepatic artery flow decreased due to a hepatic arterial buffer response.

Case report

A 6-month-old boy with biliary atresia showed excessive portal vein flow early after LDLT with a decreasing hepatic artery flow without anastomotic stenosis from postoperative day 3. The PV flow gradually exhibited a decrease at approximately postoperative day 8 and, similtaneously, hepatic artery flow exhibited improvement.

Conclusion

Because excessive portal pressure after LDLT is reversible, it has been suggested that it may be possible to prevent the progress of hepatic arterial complications if temporary portal pressure modulation can be performed for cases among the high-risk group for hepatic arterial complications.     

Hepatic arterial buffer response fails to restore hepatic oxygenation after temporary liver dearterialization in canines

BACKGROUND: Hepatic artery thrombosis is a rare but extremely troublesome condition after liver transplantation. Recently, urgent arterial revascularization has been used as rescue therapy, leading to improved graft and patient survivals. Hepatic artery ligation produces a progressive reduction in portal vein blood flow. Theoretically, a hyperemic response may be expected following hepatic artery reperfusion (hepatic artery buffer response, HABR). In this study, we tested the hypothesis that HABR can maintain adequate liver oxygenation after temporary liver dearterialization. METHODS: Seven dogs (19.7 +/- 1.2 kg) subjected to 60 minutes of hepatic artery occlusion were observed for 120 minutes thereafter. Systemic hemodynamics was evaluated through Swan-Ganz and arterial catheters, and splanchnic perfusion by portal vein and hepatic artery blood flows (PVBF and HABF) via an ultrasonic flowprobe. Liver enzymes (ALT and LDH) and systemic and hepatic oxygen delivery (DO2hepat) were calculated using standard formulae. RESULTS: Hepatic artery occlusion induced a progressive reduction in PVBF and DO2hepat. A complete restoration of HABF after hepatic artery declamping was observed; however, the DO2hepat (33.3 +/- 5.9 to 16.5 +/- 5.9 mL/min) did not return to the baseline levels. CONCLUSION: Temporary hepatic artery occlusion induced a progressive decrease in portal vein blood flow during ischemia, an effect that continued during the reperfusion period. The hepatic artery blood flow was promptly restored after declamping. However, HABR was not able to restore hepatic oxygen delivery to baseline levels during the reperfusion period.     

肝硬化肝移植术后脾脏体积及侧支循环状态对胆道并发症的影响

目的探讨终末期肝硬化患者肝移植术后脾脏体积及侧支循环状态对术后胆道并发症的影响。方法选取2005年4月至2013年2月在中山大学附属第三医院接受肝移植手术的74例患者,肝移植术前、后均行计算机体层摄影术(CT)和(或)磁共振成像(MRI)检查。根据肝移植术后脾脏体积的变化将74例患者分为3组:体积缩小至接近正常范围组(A组),体积缩小仍超出正常范围组(B组)和体积增大组(C组)。同时选取20名健康人作为正常对照组。分别统计3组患者术前与术后脾脏形态及脾静脉、门静脉直径变化的数据,并与正常对照组进行比较。记录3组患者术前与术后侧支循环开放情况及术后随访情况。结果 A组18例(24%),B组39例(53%)和C组17例(23%)。A组、B组术后侧支循环得到明显缓解,C组术后侧支循环不但未见缓解,反而较前加重。A组6例(33%)患者肝移植术后出现轻度血管并发症,1例(6%)患者肝移植术后出现轻度缺血性胆管炎。B组17例(44%)患者肝移植术后出现轻度血管并发症,6例(15%)患者出现轻度缺血性胆管炎。C组17例(100%)患者肝移植术后出现严重血管并发症,同时均伴有不同程度的胆道并发症,5例患者肝门区发现肉芽组织形成。结论终末期肝硬化患者肝移植术后胆道并发症发生率较高,肝移植术后严重的血管并发症导致的血流动力学异常是其影响因素之一。     

Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression

OBJECTIVE: To investigate the degree and mechanism of hepatic sinusoidal injury in different graft sizes in right lobe live donor liver transplantation (LDLT). SUMMARY BACKGROUND DATA: Liver grafts from living donors are likely to be small-for-size for adult recipients. Graft injury after reperfusion is common, but the mechanism and degree of injury remain unclear. The hepatic sinusoidal injury in different graft sizes and its relationship with portal hemodynamics and intragraft gene response at the early phase after reperfusion have not been studied in right lobe LDLT. METHODS: From May 2000 to November 2001, 40 adults receiving right lobe LDLT had portal pressure measured continuously before and after reperfusion. Liver biopsies were taken before and after reperfusion for detection of vasoregulatory genes (endothelin-1 and endothelial nitric oxide synthase) and heat shock genes (heat shock protein 70 and heme oxygenase-1), and electron microscope examination. Blood samples from the portal vein and suprahepatic inferior vena cava were taken for the measurement of plasma nitric oxide level. RESULTS: The recipients were grouped according to the ratio of graft weight to estimated standard liver weight: group 1 (n = 10), less than 40%; group 2 (n = 21), 40% to 60%; and group 3 (n = 9), more than 60%. The portal pressures recorded after reperfusion in group 1 were significantly higher within 30 minutes of reperfusion than those in groups 2 and 3. After reperfusion, the intragraft endothelin-1 mRNA level in group 1 increased by 161% of the basal level but decreased by 31.5% and 62% of the basal level in groups 2 and 3, respectively. The intragraft mRNA level of heme oxygenase-1 in groups 1 and 2 decreased by 75.5% and 25.3% of the basal level respectively but increased by 41% of basal level in group 3. The intragraft protein level of heat shock protein 70 decreased by 50 ng/mL after reperfusion in group 1 but increased by 12.4 ng/mL and 0.6 ng/mL in groups 2 and 3, respectively. The portal vein plasma nitric oxide level decreased more significantly after reperfusion in group 1 than in group 2. Electron microscope examination of liver biopsies in group 1 showed tremendous mitochondrial swelling as well as irregular large gaps between the sinusoidal lining cells. There were two hospital deaths in group 1 and none in the other two groups. CONCLUSIONS: Patients implanted with grafts less than 40% of standard liver weight suffered from transient portal hypertension early after reperfusion. The phenomenon was accompanied by intragraft upregulation of endothelin-1 and ultrastructural evidence of sinusoidal damage. The transient portal hypertension after reperfusion, subsequent endothelin-1 overexpression, and plasma nitric oxide level reduction, together with downregulation of heme oxygenase-1 and heat shock protein 70, may account for the small-for-size graft injury.     

肝移植中门静脉-内脏曲张静脉吻合在门静脉机化血栓患者的应用

目的:探讨门静脉-内脏曲张静脉吻合在门静脉机化血栓患者肝移植中的应用。方法:对门静脉和肠系膜上静脉均完全被机化血栓阻塞的7例患者实施肝移植,其中3例供体门静脉-曲张冠状静脉吻合;2例髂静脉搭桥供体门静脉和脾门旁曲张的静脉吻合;1例采用供体门静脉-胆总管前曲张静脉吻合;1例供体门静脉—曲张的胃网膜右静脉吻合。结果:7例手术全部成功。1例术后7d死于多脏器功能衰竭,但是门静脉血流一直通畅。1例术后6个月发现吻合口狭窄,术后9个月采用经皮肝穿刺门静脉支架置入治愈;其余患者分别随访12～22个月,门静脉血流均通畅,无狭窄或血栓形成,肝、肾功能正常。结论:肝移植中对门静脉和肠系膜上静脉均完全被机化血栓阻塞的患者,行供体门静脉-曲张内脏静脉吻合可取得良好疗效。     

Arteroportal fistulas between the accessory right hepatic, gastroduodenal and superior mesenteric arteries and portal vein: a difficult technical problem to overcome in liver transplantation

BACKGROUND: Fistulous communications between the accessory right hepatic (ARHA), gastroduodenal (GD), and superior mesenteric (SMA) arteries and the portal vein (PV) may represent a contraindication for liver transplantation (LT). MATERIAL: A patient with HCV-related liver cirrhosis and progressive liver decompensation underwent preoperative LT work-up. Doppler ultrasound (DU), Angiography and MRI revealed arteroportal fistulas (APF) and diversion of mesenteric-splenoportal flow through spontaneous splenorenal shunts (SSRS) in the systemic circulation. The patient was transplanted and the ARHA and GDA were distally sectioned; the HA was anastomosed to the donor HA; the superior mesenteric vein (SMV) was detached from the splenopancreatic venous bed by sectioning and ligating the Henle trunk, by ligating an posterior-inferior pancreatic vein and, finally, by positioning an iliac vein interposition graft between the SMV and the donor PV. The postanastomotic SMV trunk and recipient PV were ligated below and above the pancreatic head, respectively. RESULTS: Reperfusion and late liver function were good. DU and MRI studies showed an effective portal flow and the maintenance of a normal splenopancreatic vein outflow through the SSRS. DISCUSSION: APF represent a serious clinical problem, particularly in patients who need LT. The persistence of arterial flow into the PV is dangerous for the long-term liver function. A particular surgical strategy, strictly tailored to the hemodynamic conditions, has to be planned. CONCLUSIONS: Extrahepatic multiple APF would no longer to represent a contraindication to LT, although this claim needs to be confirmed in the light of further experience and a longer-term follow-up.     

Hemodynamic interaction between portal vein and hepatic artery flow in small-for-size split liver transplantation

In split-liver transplantation, the entire portal flow is redirected through relatively small-for-size grafts. It has been postulated that excessive portal blood flow leads to graft injury. In order to elucidate the mechanisms of this injury, we studied the hemodynamic interactions between portal vein- and hepatic artery flow in an experimental model in pigs. Six whole pig liver grafts were implanted in Group 1 ( n=6) and six whole liver grafts were split into right and left grafts and transplanted to Groups 2 ( n=6) and 3 ( n=6), respectively. The graft-to-recipient liver volume ratio was 1:1, 2:3 and 1:3 in Groups 1, 2 and 3, respectively. Portal vein- and hepatic artery flows were measured with an ultrasonic flow meter at 60,120 and 180 min after graft reperfusion. Portal vein pressure was also recorded at the same time intervals. Graft function was assessed at 3,6h and 12h, and morphological changes at 12h after reperfusion. Following reperfusion, portal vein flow showed an inverse relationship to graft size, while hepatic artery flow was reduced proportionately to graft size. The difference was significant among the three groups ( P<0.05). Portal vein pressure was significantly higher in group 3, compared to groups 1 and 2 ( P<0.05). Hepatic artery buffer response was significantly higher in Group 3, compared to Groups 1 and 2 in relation to pre-occlusion values ( P<0.05). Split-liver transplantation, when resulting in small-for-size grafts, is associated with portal hypertension, diminished arterial flow, and graft dysfunction. Arterial flow impairment appears to be related to increased portal vein flow.     

Comparison between two warm ischemic models in experimental liver transplantation in pigs

BACKGROUND: Experimental models of warm ischemia in liver transplantation have been employed to study the mechanisms and treatment of ischemia reperfusion injury. METHODS: We compared a control group without (group A, n = 10) versus two models of warm ischemia of liver transplants in pigs: namely, occlusion of the hepatic artery and portal vein for 30 minutes (group B, n = 23) and extraction of the liver 60 minutes after cardiac arrest (group C, n = 5). Liver function tests, coagulation studies, and liver biopsies were performed during the first 24 hours post-liver transplant. RESULTS: Clamping of the hepatic vasculature in group B produced a significant liver injury compared with the control group: elevation of the ALT and an abnormal 1-hour post-revascularization biopsy similar to that observed in the cardiac arrest group C. The transaminase levels were lower among group A animals (P <.05). But the hepatic synthetic functions as reflected in the protrombin time (PT) were not affected in group B versus group A. The alteration in PT with respect to the initial value was similar among group A and group B animals, which were significantly less than that in group C (P <.05). CONCLUSIONS: Occlusion of the hepatic artery and portal vein, a simple surgical maneuver, causes moderate damage to a liver graft but less alteration of hepatic synthetic function. Clamping of the hepatic vasculture obtains more long-term survivors after OLT than cardiac arrest.     

Experimental study of partial arterialization of the portal vein on the dearterialized liver

The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery.     

A single-center experience with retrograde reperfusion in liver transplantation

Poor graft function secondary to injury by ischemia and reperfusion remains a major problem with regard to morbidity and mortality in clinical liver transplantation (LTX). Up to one fifth of patients suffer from poor initial liver function due to severe damage to hepatocytes. This situation leads either to primary nonfunction described in approximately 6% of LTX or to slow recovery. We present a new method of reperfusion during LTX. From July 1998 to July 2002, 42 LTX in 39 recipients, (10 female, 52 years old (26–70) were performed. LTX was carried out in piggy-back technique. After completing the piggy-back anastomosis, the caval vein was declamped immediately, and retrograde low pressure reperfusion of the graft with low oxygenated venous blood was established. Portal anastomosis was performed using a running suture. In order to provide optimal retrograde liver perfusion, no clamping of the donor portal vein was done. After completing portal anastomosis, the recipient portal vein was declamped immediately. During arterial anastomosis, the transplanted liver was antegradely perfused via the portal vein. After completing hepatic artery anastomosis, declamping of the hepatic artery was done and arterial perfusion started. No backtable or in-situ-flushing except the described reperfusion technique was performed. Forty-two LTX in 39 recipients using piggy-back technique and retrograde reperfusion via the caval vein followed by antegrade reperfusion via the portal vein were performed; 38 out of 39 patients (97.44%) were alive and well at day 8 after LTX. One patient (2.56%) died of a pre-existing portal vein thrombosis on day 2 after LTX. Three patients had to undergo retransplantation for hepatic artery thrombosis (7.14%). Liver enzymes, bilirubine, prothrombine time and AT III on day 1, 3, 5 and 8 after LTX showed favourable values. Median aspartate aminotransferase (ASAT) was 219 U/l on day 1 after LTX. One-month survival rate was 95.23%, and 1-year survival rate 87.88%. Two patients died of liver-associated causes (5.12%). One patient died of a late hepatic artery thrombosis, and one more of rejection. No other severe case of rejection appeared. We can conclude that retrograde reperfusion might be highly sufficient method of removing perfusion fluid from the transplanted liver. Low pressure perfusion with low oxygenated blood might reduce the production of free oxygen radicals. Retrograde reperfusion via the caval vein and antegrade reperfusion via the portal vein seemed to lower postoperative liver enzyme values and to improve initial liver function after LTX.     

The effect of dextran 40 and blood transfusion on hepatic circulation and oxygen consumption in hemorrhagic shock

The flow in the hepatic artery and the portal vein, as well as the oxygen consumption of the liver, were studied in the pig in a standard shock model. The animals were bled to 50 mm Hg arterial pressure and kept at this pressure for 30 min. one group being treated with the shed blood and the other group with an equal volume of dextran 40. Thirty minutes after completion of the treatment, the animals were once again bled to 50 mm Hg and kept at this level for 30 min.During the first period of shock the flow in both vessels decreased to 53% of the baseline value and the oxygen consumption fell to 41% of the initial values.After treatment with the shed blood the flow in the hepatic artery and portal vein returned to preshock values and the oxygen consumption was 39% higher than the initial values. After treatment with dextran 40 the flow in the hepatic artery was 91% higher than the initial value and the flow in the portal vein was 127% higher. In spite of these high flow values, the oxygen consumption was significantly lower in the dextran 40 group. In the second period of shock flow values were reduced to approximately the same values as in the first period but the oxygen consumption was significantly lower in the dextran 40 group than in the blood transfusion group.     

Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival.

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35-42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 microg/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P = 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension.     

Acute blood leukocyte reduction after liver reperfusion: a marker of ischemic injury

INTRODUCTION: Reperfusion injury occurs after ischemic storage of the liver. The release of free radicals from endothelial cells leads to increased adherence of polymorphonuclear neutrophils to endothelium and further release of proteases and free radicals that alter the microcirculation and produce graft dysfunction. Acute blood leukocyte reduction after reperfusion may be an expression of this sequestration and activation of neutrophils within hepatic sinusoids. This study sought to evaluate whether reduction in white blood cells occurring immediately after reperfusion was a marker of poor graft preservation and postoperative dysfunction. METHODS: The leukocyte count was evaluated at the end of anhepatic phase and at 5 minutes after reperfusion among 65 patients undergoing liver transplantation. Group A included patients with a leukocyte reduction between the two phases greater than 50%; group B, patients with less than 50%. Hepatic enzymes, blood lactate (60 and 120 minutes after graft reperfusion) and factor V and VII and bilirubin levels (daily for 15 days after transplantation) were compared between groups to assess graft injury and postoperative dysfunction. RESULTS: Alanine aminotransferase levels were significantly higher among group A than group B at both 60 and 120 minutes after graft reperfusion. No differences were observed in lactate, and factor V and VII levels. Total bilirubin was significantly higher among group A than group B patients at 10 and 15 days postoperative. CONCLUSIONS: The acute blood leukocyte reduction after reperfusion, probably due to sequestration and activation into hepatic sinusoids, seemed to be an early intraoperative marker for poor graft preservation and function.     

Does middle hepatic vein omission in a right split graft affect the outcome of liver transplantation? A comparative study of right split livers with and without the middle hepatic vein.

Preservation of the middle hepatic vein (MHV) for a right split liver transplantation (SLT) in an adult recipient is still controversial. The aim of this study was to evaluate the graft and patient outcomes after liver transplantation (LT) using a right split graft, according to the type of venous drainage. From February 2000 to May 2006, 33 patients received 34 cadaveric right split liver grafts. According to the type of recipient pairs (adult/adult or adult/child), the right liver graft was deprived of the MHV or not. The first group (GI, n = 15) included grafts with only the right hepatic vein (RHV) outflow, the second (GII, n = 18) included grafts with both right and MHV outflows. The 2 groups were similar for patient demographics, initial liver disease, and donor characteristics. In GI and GII, graft-to-recipient-weight ratio (GRWR) was 1.2 +/- 0% and 1.6 +/- 0.3% (P < 0.05), and cold ischemia time was 10 hours 55 minutes +/- 2 hours 49 minutes and 10 hours 47 minutes +/- 3 hours 32 minutes, respectively (P = not significant). Postoperative death occurred in 1 patient in each group. Vascular complications included anastomotic strictures: 2 portal vein (PV), 1 hepatic artery (HA), and 1 RHV anastomotic strictures; all in GI. Biliary complications occurred in 20% and 22% of the patients, in GI and GII, respectively (P = not significant). There were no differences between both groups regarding postoperative outcome and blood tests at day 1-15 except for a significantly higher cholestasis in GI. At 1 and 3 yr, patient survival was 94% for both groups and graft survival was 93% for GI and 90% for GII (P = not significant). In conclusion, our results suggest that adult right SLT without the MHV is safe and associated with similar long-term results as compared with those of the right graft including the MHV, despite that early liver function recovered more slowly. Technical refinements in outflow drainage should be evaluated in selected cases.     

Hemodynamic profiles during piggyback liver grafts using arterial or portal revascularization

BACKGROUND: The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data. STUDY DESIGN: Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure. RESULTS: Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups. CONCLUSIONS: Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.