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.     

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.     

Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia.     

FK409 ameliorates ischemia-reperfusion injury in heart transplantation following 12-hour cold preservation.

OBJECTIVE: FK409 is the first spontaneous nitric oxide donor to increase plasma guanosine 3':5'-cyclic monophosphate. We designed this study to investigate whether the administration of FK409 during reperfusion ameliorated ischemia-reperfusion injury and enhanced post-transplant graft function in orthotopic heart transplantation following 12-hour cold preservation in a canine model. METHODS: We used 10 pairs of adult mongrel dogs, weighing 9.5 to 13.5 kg. Following cardiac arrest using cardioplegia, we washed out the coronary vascular beds with cold University of Wisconsin solution followed by 12-hour preservation. After preservation, we performed orthotopic transplantation. The experimental animals were divided into 2 groups. In the FK group (n = 5), FK409 (5 microg/kg/min) was administered intravenously, beginning 15 minutes before the onset of reperfusion and continuing for 45 minutes after reperfusion. In the control group (n = 5), saline vehicle was administered in the same manner. Two hours after transplantation, we assessed cardiac function, including cardiac output, left ventricular systolic pressure (LVP), and the maximum rates of positive and negative increase of LVP (+/-LV dP/dt) by comparing the recovery rate (%) of the cardiac function of the donor animal. We measured endothelin-1 levels in blood obtained from a catheter inserted into the coronary sinus 30, 60, and 120 minutes after reperfusion. RESULTS: Cardiac output was higher in the FK group than in the control group, but the difference was not significant (p = 0.08). Left ventricular systolic pressure and +/-LV dP/dt were significantly (p < 0.05) higher in the FK group than in the control group. Endothelin-1 levels were significantly (p < 0.05) lower in the FK group than in the control group 30 minutes after reperfusion. Transmission electron microscopy showed that the basal lamina of capillary vessels, glycogen granules, and mitochondrial structure were well-preserved in the FK group. CONCLUSIONS: In orthotopic transplantation models, FK409 is effective in ameliorating ischemia-reperfusion injury following preservation and in enhancing post-transplant cardiac function.     

FK409对大鼠肝脏移植缺血再灌注损伤后JAK2/STAT3信号通路的影响

目的 探讨FK409对人鼠肝脏移植缺血再灌注损伤后细胞凋亡及JAK2,STAT3表达的影响.方法雄性SD 大鼠60只,随机分为假于术组、牛理盐水干预组、FK409干预组,采用Kamada's袖套法建立大鼠原位肝移植模型.干预组于新肝开放前分别鼠尾静脉注射FK409 2 mg/kg或等量生理盐水,于24 h后RT-PCR及免疫组织化学方法检测JAK2,STAT3表达水平的变化;利用原位缺口未端标记法(TUNEL法)研究肝细胞凋亡的变化.结果 与生理盐水干预组相比,FK409干预组JAK2,STAT3表达明显减少(P＜0.05);凋亡细胞也减少(P＜0.05).结论 FK409尚能通过抑制与炎性细胞因子及氧化应激有密切关系的JAK2/STAT3信号转导通路显著减轻大鼠肝移植缺血再灌注损伤后组织损伤.     

Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes

BACKGROUND: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. HYPOTHESIS: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. MAIN OUTCOME MEASURES: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). SETTING: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). RESULTS: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P =.04; 15-minute: 96 vs 127 mm Hg, P =.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the anhepatic phase (5-minute: 15.1 vs 9.3, P =.02; 10-minute: 16.1 vs 9.3, P =.03; 15-minute, 13.5 vs 9.3, P =.03; 20-minute: 13.4 vs 9.3, P =.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P =.02; 10-minute: 16.1 vs 10.3, P =.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3, P =.02; 10-minute: 14.9 vs 6.6, P =.02; 15-minute: 14.8 vs 5.5, P =.02; 20-minute: 13.1 vs 7.0, P =.02; 30-minute: 13.2 vs 8.8, P =.04; 40-minute: 14.6 vs 7.1, P =.02). Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. CONCLUSIONS: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.     

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.     

Review of the surgical approach to prevent small-for-size syndrome in recipients after left lobe adult LDLT

Left lobe liver grafts increase the donor safety in adult-to-adult living-donor liver transplantation (ALDLT). However, the left lobe graft provides about 30–50 % of the required liver volume to adult recipients, which is insufficient to sustain their metabolic demands, which can lead to small-for-size syndrome (SFSS). Transient portal hypertension and microcirculatory hemodynamic derangement, apart from outflow obstruction, during the first week after reperfusion are the critical events associated with small-for-size graft transplantation. The incidence of SFSS in left lobe ALDLT can be decreased by increasing the left lobe graft volume by effective utilization of the caudate lobe with preserved vascular supply, by modulating the portal pressure with splenectomy or a porto-systemic shunt or by hepatic venous outflow reconstruction to prevent the development of venous congestion. In this review, we discuss the pathophysiology of SFSS and the various surgical strategies that can be performed to prevent SFSS in an effort to enhance the donor safety during living-donor liver transplantation.     

Reversible hepatofugal portal flow after liver transplantation using a small-for-size graft from a living donor

We describe a case of reversible hepatofugal portal flow 1 week after transplantation of a small-for-size liver graft from a living donor. A transient increase in intrahepatic portal vascular resistance was the suspected cause. The portal venous flow normalized after residual collateral channels had been interrupted surgically. The patient was discharged on the 90^th postoperative day. Liver transplant clinicians should be aware that hepatofugal flow can occur with small-for-size liver grafts, despite sufficient portal venous flow immediately after transplantation. Received: 8 March 2000 Revised: 26 September 2000 Accepted: 5 May 2001     

Antiinflammatory properties of IL-10 rescue small-for-size liver grafts.

The present study aims to investigate the potential therapeutic role of interleukin-10 (IL-10) in small-for-size liver transplantation. A syngenic rat orthotopic liver transplantation model was performed using either whole or 40% liver volume of Lewis rats as grafts according to the experimental design. IL-10 was given to the 40% grafts right after reperfusion, and also at 24 and 48 hours after transplantation. When no treatment was given, less than 40% of the small-for-size grafts survived indefinitely, whereas IL-10 treatment could increase the long-term survival rate of the small-for-size grafts to 80%. The 40% grafts presented with extensive areas of necrosis and increased number of apoptotic cells at the early phases after reperfusion. In addition, upregulation of plasma protein carbonyl content (PCC) levels was also detected in the 40% graft group. IL-10 treatment suppressed the upregulation of allograft inflammatory factor-1 (AIF-1) on macrophages in the 40% grafts, and at the same time, decreased the levels of plasma PCC, and improved the histology and function of the 40% grafts. The expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-alpha, and caspase 9 in the 40% grafts were upregulated after reperfusion, whereas the augmentation could be suppressed by the administration of IL-10. Finally, IL-10 culture could block AIF-1-mediated NO production and downregulate the expression of iNOS and TNF-alpha in a macrophage cell line. In conclusion, IL-10 rescued the small-for-size liver grafts by its antiinflammatory properties, through inhibition of AIF-1 mediated proinflammatory and proapoptotic activities of the macrophages during the early period after ischemia/reperfusion.     

Cardioprotective effects of FK409, a nitric oxide donor, after isolated rat heart preservation for 16 hours

BACKGROUND: We examined the cardioprotective effects of FK409, a nitric oxide donor, after isolated rat heart preservation. METHODS: FK409 was administered to the hearts in pretreatment (FK409-1 group), during ischemia (FK409-2), or during reperfusion (FK409-3). The combined nitrate and nitrite level, coronary flow, cardiac function, coronary vasodilatory response, creatine kinase (CK), and myocardial water content were evaluated after the hearts had been preserved in University of Wisconsin solution at 0 degrees C for 16 hours. RESULTS: The release of nitrate and nitrite increased in reperfusion between the 20-to-40-second measurement and the measurement at 40 minutes, and the recovery of cardiac function was significantly improved in the FK409 groups. The coronary vasodilatory response to acetylcholine chloride was enhanced in the FK409-1 and FK409-2 groups. CK release decreased in FK409 groups after 15 minutes in reperfusion. CONCLUSIONS: This study suggests that FK409 has the best protective effect on cardiac function and coronary endothelial function when it is administered in the ischemic period, a less protective effect when administered during pretreatment, and the least protective effect when FK409 is given during reperfusion after heart preservation for 16 hours.     

Mesorenal shunt using inferior mesenteric vein and left renal vein in a case of LDLT

Adult-to-adult living donor liver transplantation (LDLT) has become an established treatment option around the world. However, small-for-size graft syndrome remains one of the most serious complications affecting transplant outcomes. Excessive portal hypertension and overperfusion have been shown to play a causative role in this graft injury. Recently, portal hypertension per se has been considered detrimental to graft function, and thus to be avoided for successful outcomes after LDLT. We constructed a mesorenal shunt with anastomosis of the inferior mesenteric vein and left renal vein in the case of an LDLT recipient who showed high portal vein pressure after graft reperfusion. The inferior mesenteric vein is close to the left renal vein, and the anastomosis was obtained with relative ease. The shunt was effective in decreasing portal vein pressure, and postoperative graft function was satisfactory. This new method represents an option for attenuating portal hypertension when elevated portal vein pressure is observed in adult LDLT after graft reperfusion.     

Changes in portal vein flow after adult living-donor liver transplantation: Does it influence postoperative liver function?

In adult living donor liver transplantation, using small grafts in cirrhotic patients with severe portal hypertension may have unpredictable consequences. The so-called small-for-size syndrome is present in most series worldwide. The goal of this study was to prospectively evaluate the influence of hemodynamic changes on postoperative liver function and on the percentage of liver volume increase, in the setting of living donor liver transplantation. Twenty-two consecutive adult living donor liver transplantations were performed at our institution in a 2-year period. We measured right portal flow and right hepatic arterial flow with an ultrasonic flow meter in the donor, and then in the recipient 1 hour after reperfusion. Postoperative liver function was measured by daily laboratory work. We also performed duplex ultrasounds on postoperative days 1, 2, and 7. Liver volume increase was estimated by magnetic resonance imaging graft volumetry at 2 months posttransplantation. We compared the blood flow results with the immediate liver function and its liver volume increase rate at 2 months. There was a significant increase in portal flow in the recipients compared with the donors (up to fourfold in some cases). Higher portal flow increase rates significantly correlated with faster prothrombin time normalization and faster liver volume increases. Median graft volume increase at 2 months was 44.9%. The increase in blood flow to the graft is well tolerated by the liver mass not affecting hepatocellular function as long as the graft-to body weight ratio is maintained (>0.8) and adequate outflow is provided. (Liver Transpl 2003;9:564-569.)     

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

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

基质金属蛋白酶-9 与小体积移植肝早期损伤的相关性研究

目的 观察不同体积肝移植术后早期移植肝内基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达及活化特点,探讨MMP-2和MMP-9在小体积移植肝早期损伤中的作用机制. 方法 随机将108只SD大鼠分成3组,每组36只.分别为:全肝(100%肝体积)移植组、半肝(50%肝体积)移植组和小体积肝(25%肝体积)移植组.分别检测移植肝再灌注后0.5、6、12、24、48、72 h的肝功能及移植肝组织中丙二醛(MDA)和髓过氧化物酶(MPO)浓度,观察移植肝组织病理学特征,并运用双抗夹心酶联免疫吸附试验(ELISA)、实时定量聚合酶链反应(PCR)、明胶酶谱和免疫组织化学方法检查移植肝中MMP-2和MMP-9的表达情况. 结果 与全肝和半肝移植组比较,小体积肝移植组再灌注后6～24 h MMP-9表达明显升高;而且MMP-9活化和表达增高伴随着移植肝功能损害和严重的缺血再灌注损伤.MMP-9早期表达都集中在移植肝门静脉周围,与门静脉高灌注密切相关. 结论 MMP-9表达升高是小体积移植肝早期重要的致损伤因素;肝移植术后门静脉高灌注可能是触发MMP-9活化和表达的重要原因.     

Impaired hepatic regeneration by ischemic preconditioning in a rat model of small-for-size liver transplantation

OBJECTIVE: Graft size is one of the major risk factors in adult-to-adult living donor liver transplantation and rapid regeneration is an essential post-operative requirement. Ischemic preconditioning (IPC) has been shown to be an effective strategy in the reduction of hepatic ischemia-reperfusion injury and stimulation of liver regeneration. This study was designed to evaluate the effects of IPC on liver regeneration in small-for-size liver grafts. METHODS: We employed a rat orthotopic liver transplantation model using small-for-size (30%) grafts, in the presence or absence (control) of IPC (10 min of ischemia followed by 15 min of reperfusion). Survival rate, graft injury, hepatocellular proliferation, cell cycle progression, Stat3 activation, as well as TNF-alpha and IL-6 expression were assessed. RESULTS: IPC significantly enhanced the extent of graft injury and hindered hepatic regeneration in small-for-size liver grafts. The 7-day survival rate was also reduced by IPC, but failed to reach statistical significance. IPC did not affect TNF-alpha levels, but significantly decreased the elevation of IL-6 after reperfusion. These findings were correlated with down-regulation of cyclin E and cyclin D1, and decreased numbers of PCNA-positive nuclei in IPC grafts. These results were inconsistent with Stat3 activation, as P-Stat3 exhibited a stronger and prolonged pattern of expression in the IPC group, compared to controls. CONCLUSIONS: Ischemic preconditioning may impair liver regeneration in small-for-size liver grafts by decreasing IL-6 and blunting cell cycle progression, through a mechanism at least partially independent of Stat3.     

Surgical procedures for decompression of excessive shear stress in small-for-size living donor liver transplantation--new hepatic vein reconstruction

We have reported that acute elevation of portal pressure, reflecting wall shear stress of sinusoidal endothelial cells, triggers liver regeneration after partial hepatectomy and that excessive portal hypertension induces liver failure. For prevention of excessive shear stress in small-for-size living donor liver transplantation (LDLT), we developed a new hepatic vein reconstruction to expand the anastomotic site. Fourteen adult patients, who underwent LDLT, were divided into two groups: previous end-to-end hepatic vein reconstruction in nine patients (group P) and the new method in five patients (group N). The outside middle and left hepatic veins of the graft were incised and enlarged to 40 mm. The vena cava was cut 40 mm longitudinally. The graft was positioned a quarter turn counterclockwise with the hepatic vein of the graft anastomosed end-to-side to the vena cava longitudinally. Postoperative portal pressures and serum total bilirubin levels of these two groups showed portal pressure in group N to rapidly decrease below 25 cm H2O following LDLT. No cases showed posttransplanted hyperbilirubinemia above 10 mg/dL in group N; however, all cases were small-for-size grafts. Moreover, serum total bilirubin levels in group N were significantly lower than those in group P. This procedure is simple despite not using a venous patch. If the hepatic vein is narrow or obstructed, such as in Budd-Chiari syndrome, the procedure is applicable. Even in small-for-size grafts, excessive tension did not occurred at the portal vein or hepatic artery anastomoses. Moreover, it is possible to avoid outflow block and posttransplanted hyperbilirubinemia.     

附加门体分流术对小体积移植肝保护作用的实验研究

目的 研究附加门体分流术对小体积移植肝的保护效果.方法 建立巴马小型猪小体积肝移植模型,将15只小型猪平均分为3组:(1)A组,小体积肝移植组(对照组);(2)B组,远端脾肾分流术+小体积肝移植组;(3)C组,肠腔H形分流术+小体积肝移植组.手术后观察动物7 d存活率,动态监测肝功能生化指标、自由门静脉压、门静脉血流量(PBF)以及移植肝组织病理学改变.结果 动物7 d存活率分别为:A组1/5,B组3/5,C组5/5.A组动物移植肝复流后自由门静脉压立即升高,高峰达(28.6±2.07)mm Hg(1 mm Hg=0.133 kPa),复流1 h后单位肝组织PBF达(3.56±0.1 1)ml·min-1·g-1;移植肝组织病理学改变严重,包括肝细胞气球样变或肝细胞坏死、肝窦淤血、肝实质出血.B、c组中动物肝功能酶学指标有所改善.移植肝复流后自由门静脉压显著低于A组水平(P<0.05),PBF保持相对平稳.移植肝组织病理学病变明显减轻.结论 附加门体分流术可能可以避免小体积移植肝的损伤.     

小体积肝移植的基础研究进展

目的介绍小体积肝移植术后移植物损伤机理及移植物保护措施。方法复习和总结了相关文献资料并作综述。结果小体积肝移植术后过高的门静脉压力导致移植物机械性损伤,并通过改变肝窦微循环状态及激活各类细胞因子使移植物损伤进一步加重。通过手术或药物的方法降低门静脉压力可对移植物起一定的保护作用。结论了解小体积肝移植术后移植物损伤机理对于临床提高活体肝移植的效果具有积极的意义。