猪原位肝移植术中体外静脉转流途径的实验研究

目的　探讨猪原位肝移植手术中体外静脉转流的应用及不同转流途径对血流动力学的影响。方法　选择50只健康家猪按体重接近原则配对分为供体组与受体组进行 2 5例原位肝移植手术 ,受体组无肝期采用不同体外静脉转流途径 ,其中A组 (1 6只 )经门静脉插管 ,B组 (9只 )经脾静脉插管。术中连续监测A、B两组动物的血流动力学变化。结果　术后 2 4h ,A组存活 1 4只 ,B组 9只全部存活。A组血流动力学在无肝期开始及结束时均出现明显波动 ,平均动脉压和中心静脉压下降 ,心率上升 ;B组在整个无肝期内血流动力学保持平稳 ,两组间比较差异有显著性意义 (P<0 .0 5)。结论　猪原位肝移植术中应用体外静脉转流 ,有利于维持血流动力学稳定 ,而经脾静脉插管转流较经门静脉插管转流具有更大的优越性     

原位肝移植的静脉-静脉转流

目的评价体外静脉-静脉转流技术对原位肝移植术中无肝期血流动力学、生化、体温和肾功能的影响。方法28例原位肝移植术中使用JostraRotaFlow离心泵、热交换器、边缘肝素化进行开放式静脉-静脉转流。结果体外静脉-静脉转流时间（136.7±60.4）min,灌注流量0.5～3.5L/min,动脉压维持在（82.3±3.3）mmHg,中心静脉压维持在（8.12±4.05）cmH     

猪原位肝移植术体外静脉-静脉转流方法的探讨

目的 体外静脉转流应用于原位肝移植术，观察血流动力学及激活全血凝固时间变化。方法 杂种猪40头，随机分为供体组和受体组，采用人工心肺机单泵，在非全身肝素化下，于实验猪原位肝移植术无肝期行门静脉、下腔静脉至上腔静脉的转流，测定术中血流动力学和激活全血凝固时间的指标。结果 术中血流动力学除在无肝期及开放后早期时间内有明显波动外，余无特殊变化，此外转流期部分肝素化，并不影响转流后凝血功能。体外静脉转流量达1000ml／min，整个过程血流动力学波动小，而静脉转流量小于500ml／min则术中血流动力学不能维持。结论 在原位肝移植过程中，良好的外静脉转流对维持血流动力学稳定有重要意义，转流后及时用鱼精蛋白中和肝素可促进凝血功能正常。     

猪原位肝移植体外静脉转流中门脉系统插管的选择

目的比较在猪原位肝移植体外静脉转流中行门静脉插管或脾静脉插管对血流动力学的影响。方法选健康美国杜洛克猪60头，配对施行原位肝移植术，根据术中转流时门脉系统插管的不同．随机分为两组．即门静脉插管组(n=15)和脾静脉插管组(n=15)。术中连续监测两组动物血流动力学指标的变化。结果门静脉插管组15例中死亡2例．其中1例死于术中转流不畅，1例死于DIC；脾静脉插管组15例中死亡1例，死于失血性休克。脾静脉插管组无肝期为(44．5土7．6)min，明显短于门静脉插管组的(51．5土8．7)minoⅢ、Ⅳ期门静脉插管组血流动力学改变与脾静脉插管组相比差异有显著性意义(P＜O．05)。结论在猪原位肝移植体外静脉转流中采用脾静脉插管转流能缩短无肝期，保持术中血流动力学的相对稳定，减少术后相关并发症的发生，是一种有效的静脉转流途径。     

巴马小型猪非静脉转流原位肝移植模型的建立

目的建立重复性和稳定性好的巴马小型猪非静脉转流原位肝移植模型。方法选用12只巴马小型猪随机分为供体组(n=6)和受体组(n=6),行非静脉转流原位肝移植术,术中缩短无肝期的时间、维持无肝期血压稳定以及加强术中麻醉与体液管理。观察并记录受体的手术时间、无肝期、存活情况,监测术中心率、平均动脉压(MAP)、动脉血气分析改变,检测围手术期肝功能情况。结果 6只巴马小型猪中,1只术中死亡移植失败,其余5只的手术时间为(247±27)min,无肝期为(46±4)min,其中3只存活2周以上。与无肝前期相比,无肝期动物心率明显加快,MAP明显降低至(46±6)mmHg,血液pH值、剩余碱(BE)、HCO3-均下降,血清K+升高(均为P0.05)。新肝期巴马小型猪MAP上升,心率变慢,血液pH值、BE、HCO3-升高,血清K+降低(均为P0.05)。关腹时MAP及血气各指标及血清K+基本恢复至无肝前期水平。与术前相比,术毕时丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)明显升高(均为P0.05),AST升高变化最明显,术后第2日开始逐渐下降。γ-谷氨酰转移酶(GGT)无升高变化,总胆红素(TB)术后第5日急剧升高。与术前相比,术毕时总蛋白(TP)、白蛋白(ALB)均明显下降(均为P0.05),术后第1日开始逐渐回升。结论非静脉转流巴马小型猪原位肝移植模型手术便捷、重复性高、存活率高,可以作为标准化的肝移植模型。     

小型猪小体积肝移植模型的建立

目的研究构建成熟稳定小型猪小体积肝移植模型的方法。方法选用体重一致的广西巴马小型猪20只,按照随机原则分为供体组和受体组各10只。在获取供肝的过程中即进行减体积操作,切除左半肝并保留肝中静脉主干。受体采用经典原位非静脉-静脉转流法行小体积肝移植。记录受体肝移植的手术时间,供肝热缺血时间、冷缺血时间,受体无肝期时间。观察移植术后2周存活情况及手术相关并发症。结果手术时间5～7h,平均6h;供肝热缺血时间2～3min;冷缺血时间(116±16)min;无肝期时间(35±4)min。术中小型猪均无死亡。10只受体猪中,2只死于手术相关并发症,其中1只于术后10h死于肝断面出血,另1只于术后2d死于切口疝。其余8只受体猪皆存活超过2周,2周存活率达80%,均未发生手术相关并发症。结论在供体手术中切除左半肝并保留肝中静脉主干,受体采用经典原位非静脉-静脉转流法行小型猪小体积肝移植模型构建是可行且稳定的。     

小型猪原位肝移植模型的建立与评价

目的 探讨建立放弃静脉转流的小型猪原位肝移植模型的可行性。方法 选用广西巴马小型猪(3-6月龄,8-11kg)为实验动物,共实施原位肝移植10例次。供体肝脏游离、冷灌注、切取、修整以及UW保存按常规方法进行。受体术中肝脏游离后夹闭肝上、肝下下腔静脉和门静脉并切除受体肝脏,各血管断端与供肝相应血管进行端端吻合,肝上下腔静脉和门静脉吻合完毕即开放肝脏血流,在此过程中未使用静脉转流,此后吻合肝动脉、胆管。结果 本组10例次肝移植手术后一周存活率90％(9/10),无肝期时间31.3±2.67min,无肝期血压显著下降(MAP4.5±1.58kPa)但肝血流开放后能较快恢复并渐趋平稳。结论 本组结果表明,非静脉转流条件下的小型猪肝移植模型是一操作方便、易于复制同时又具有较好重复性和稳定性的大动物肝移植模型,能应用于肝移植的系列实验研究。     

原位肝移植术中的体外静脉转流

目的观察体外静脉-静脉转流对患者血流动力学的影响。方法原位异体肝移植患者14例,术中使用离心泵,部分肝素化方法行体外静脉转流。结果体外静脉转流时间（98.9±23.6）min,转流量（1168±260）ml/min,转流期及新肝5分钟心排血量（CO）明显下降,但仍维持在正常水平,体循环阻力（SVR）、肺循环阻力（PVR）转流30分钟后明显增加,心率（HR）、平均动脉压（MAP）、中心静脉压（CVP）、平均肺动脉压（MPAP）、肺毛细血管楔压（PCWP）等在转流期均无明显变化,新肝早期MAP明显下降,SVR明显增加。结论无肝期采用离心泵行体外静脉转流,有助于稳定血流动力学,但新肝早期仍有明显血压下降,主要通过适量快速泵灌注全血来纠正。     

不作转流的经典式原位肝移植术（附15例报道）

目的：观察不转流的经典工原位肝移植的效果,分析不转流对胃肠道及肾脏功能的影响。方法：1999年以来我所共为15例终末期肝病患施行了不转流的经典式原位肝移植术,术中门静阻断时间平均为40．5min,下年以来我所共为15例终末期肝病患施了不转流的经典式原位肝移植术,术中门静脉阻断时间平均为40.5min,下腔静脉阻断时间58.7min;无肝期血压维持在78-96/52-64mmHg.开放门静后从肝下下腔静放血150-20ml结果:15例一月内除1例术后7天死于DIC外,余14例无一例发生与不转流相关的胃肠道和肾功能明显损害的并发症.结论:不转流经典式原位肝移植若无肝期小于1h和血压在80/50mmHg以上,并不增加胃肠道和肾脏功能损害等产发症,有手术时间短和节省费用等优点.     

非转流小型猪原位肝移植模型的建立及评价

目的建立标准化程度高、重复性和稳定性好的小型猪原位肝移植模型。方法选巴马小型猪为实验动物,在非体外静脉转流条件下行同种异体原位肝移植术,观察动物存活率及术中血流动力学、血气和生化指标的改变。结果在非体外静脉转流条件下行同种异体原位肝移植20例,平均手术时间为(181±25.8)min,平均无肝期(28.4±3.2)min。在无肝期,血流动力学和代谢发生急剧变化:平均动脉压(MAP)从无肝前期的(14.59±1.68)kPa(1cm H2O=0.098kPa)降至(5.87±0.91)kPa,中心静脉压(CVP)从(0.66±0.11)kPa降至(0.27±0.10)kPa;体温、pH、剩余碱(BE)及HCO3ˉ显著降低,心率及血清K+显著升高(P<0.05);随着门静脉和下腔静脉血流的开放,血流动力学及代谢紊乱即逐渐恢复正常。动物1周存活率为90%,16头动物存活2周以上。肝功结果:术后第1天ALT、AST和TBIL显著升高并达到峰值,第2天开始下降,第7天降至麻醉后水平。结论非转流条件下的小型猪同种异体原位肝移植模型具有标准化程度及手术成功率高、重复性和稳定性好的优点,是大型动物肝移植系列研究的理想动物模型。     

Simplified technique of orthotopic liver transplantation in pigs

BACKGROUND: Pig models have become common in transplantation immunological research. However, in pigs, clamping of the venous splanchnic system during orthotopic liver transplantation (OLT) is responsible for high morbidity and mortality rates; therefore, the use of venovenous bypass (VVB) is advocated. Because venous bypass can also cause specific complications, a simplified method for OLT in pigs has been developed and evaluated in terms of morbidity and mortality. METHODS: Twenty-three OLTs were performed between pairs of inbred miniature swine. Donor and recipient pairs (weighing 20-35 kg) were selected at 3-6 months of age. In the donor, the portal vein, infrahepatic vena cava, and suprahepatic vena cava were dissected, whereas the hepatic artery was preserved in continuity with the coeliac trunk and the abdominal aorta up to the iliac bifurcation. In situ cold perfusion was then performed. The recipient was prepared simultaneously by another surgical team. After total hepatectomy and complete portal and caval clamping, the suprahepatic vena cava and portal vein were sutured; VVB was not used. After completion of both venous sutures, the liver graft was reperfused. The infrahepatic vena cava was then anastomosed and unclamped. The donor aorta conduit was implanted end-to-side to the recipient infrarenal aorta, and the biliary reconstruction consisted of a cholecystojejunostomy with a Roux-Y loop. RESULTS: Twenty of 23 (87%) animals survived more than 1 week (7-483 days). The mean anhepatic time was 29.6+/-4.12 min. Although severe hypotension was noted during the anhepatic phase, the hemodynamic status rapidly recovered and stabilized after graft reperfusion. CONCLUSION: Simplified technique without VVB is appropriate for successfully achieving OLT in pigs.     

Right lobe living donor liver transplantation with or without venovenous bypass

BACKGROUND: Venovenous bypass was considered necessary to maintain haemodynamic stability and avoid splanchnic and retroperitoneal congestion during the anhepatic phase of liver transplantation. It was essential for right lobe living donor liver transplantation (LDLT) in which the inferior vena cava needed to be cross-clamped to construct wide and short hepatic vein anastomoses. However, many complications related to venovenous bypass have been reported. This study aimed to determine whether venovenous bypass was necessary for right lobe LDLT. METHODS: Between June 1996 and June 2001, 72 patients underwent right lobe LDLT. The outcomes for the first 29 patients who had venovenous bypass during the operation were compared with those of the remaining 43 patients who did not have venovenous bypass. In patients without bypass, blood pressure was maintained during the anhepatic phase by boluses of fluid infusion and vasopressors. RESULTS: Compared with patients undergoing operation without venovenous bypass, patients who had venovenous bypass required significantly more blood, fresh frozen plasma and platelet infusion, and had a lower body temperature; their postoperative hepatic and renal function in the first week was worse than that in patients who did not have a bypass. The time to tracheal extubation was longer and the incidence of reintubation for ventilatory support was higher with venovenous bypass. Six of the 29 patients with venovenous bypass died in hospital, compared with two of the 43 patients without a bypass (P = 0.05). By multivariate analysis, the lowest body temperature during the transplant operation was the most significant factor that determined hospital death. CONCLUSION: Venovenous bypass is not necessary and is probably harmful to patients undergoing right lobe LDLT, and should therefore be avoided.     

Orthotopic abdominal multivisceral transplantation without venovenous bypass in pigs

BACKGROUND: Because venovenous bypass (VVB) can cause specific complications, a simplified orthotopic abdominal multivisceral transplantation (MVTX) technique without VVB in pigs has been evaluated in terms of morbidity and mortality. MATERIALS AND METHODS: Outbred large-white pigs weighing 25 to 40 kg of random sex underwent MVTX operation. After in situ cold perfusion through the aorta and superior mesenteric vein, the multivisceral allograft was procured from the donor and tailored at the back table. The multivisceral allograft, including liver, pancreas, stomach, duodenum, and proximal 2 m of jejunum, was en bloc transplanted into recipient after resection of entire foregut and midgut; VVB was not used. We analyzed the hemodynamic change, arterial blood gas data, and fluid requirements intraoperatively. RESULTS: Among 25 MVTXs, 19 (76%) animals survived after the operation. Without using an immunosuppressant, postoperative survival time was 2 to 146 hours. Ten recipient pigs died within 24 hours. Seven animals were lost between postoperative days 2 and 5. Two pigs survived for more than 5 days. The recipient pigs were mostly in a state of hypovolemic shock and metabolic acidosis during the reperfusion phase. CONCLUSIONS: Despite a high morbidity and mortality, the simplified technique without VVB is feasible to successfully achieve MVTX in the pig.     

体外静脉转流原位肝移植一例

目的 采用肝脏移植治疗直硬化的原发性肝癌。方法 在动物实验的基础上,供肝发取,４℃ＵＷ液灌注和保存。手术采用体外静脉转流肝脏移植技术。结果 手术历时１２小时,无肝期１００分钟术中血流动力学平稳,术后肾功能正常。结论肝移植治疗肝硬化肝癌本外静脉转汉是十分重要的。     

小型猪非转流原位肝移植的围手术期处理

目的:探讨中国小型猪非转流条件下原位肝移植的围手术期特点，以建立成熟、稳定的移植模型。方法:通过预实验组8例次和实验组18例次非转流条件下中国小型版纳猪原位肝脏移植术，观察围手术期血流动力学及重要代谢指标的变化，改进围手术期处理措施，总结围手术期处理特点。结果:预实验组8例次均在术后当天死亡。实验组18例次无术中死亡，术后7d存活率为88.9%。实验组平均手术时间（179.6±14.3）min，平均无肝期（27.3±3.4）min。无肝期血流动力学及生化代谢波动明显。术后当天麻醉清醒，术后约3～5h开始自行排尿，术后第3天正常进食。结论:手术中无肝期时间的缩短及血流动力学的相对稳定是非转流条件下猪原位肝移植成功的关键。     

Perioperative cytokines during orthotopic liver transplantation without venovenous bypass

Since most of studies investigating cytokine levels during human orthotopic liver transplantation used venovenous bypass (VVB), it may be difficult to distinguish between the increase in proinflammatory mediators induced by VVB, by ischemia-reperfusion injury or by splanchnic venous congestion in the anhepatic phase. The goal of this investigation was to assess the levels of interleukin-6 (IL-6) and soluble interleukin-2 receptors (sIL-2r) during OLT procedures routinely performed without VVB. PATIENTS AND METHODS: Twenty-one consecutive patients underwent OLT with cross clamping of the inferior caval vein without VVB. Soluble IL-2r concentrations were measured by means of luminescence enzyme immunometric assay and IL-6 by means of a sequential immunometric assay. Time points (TP) of sampling were before induction of anesthesia (TP1), after cross-clamping of the inferior vena cava (TP2), 15 minutes after reperfusion (TP3), and 24 hours after the transplant procedure (TP4). RESULTS: Soluble IL-2r increased significantly 24 hours after transplantation (P =.02) compared to TP1, TP2, and TP3. IL-6 increased significantly during the anhepatic period (TP2 vs TP1, P =.003) and again in the reperfusion period (TP2 vs TP3, P =.002). Twenty-four hours after surgery IL-6 declined significantly (TP3 vs TP4, P =.001), but remained significantly higher (P = 0.04) compared to TP1. Furthermore, we examined the relative changes (DeltaTP %) in perioperative levels of cytokines compared with those previously published in studies using VVB. We observed higher values of DeltaTP % of IL-6 in TP2 and TP4 among our group of patient without VVB. The data on sIL-2r were similar, suggesting no major effects of the operative technique on sIL-2r levels. CONCLUSION: The two interleukins showed different perioperative trends. Our data suggest that cross clamping contributes more to cell activation, namely, increased release of IL-6 in the anhepatic phase than the use of VVB. However, no major differences were observed during the reperfusion period. The extent of clinical effect on graft function of higher IL-6 levels in the anhepatic period among recipients not supported with VVB remains to be clarified.     

Orthotopic liver transplantation with selective use of venovenous bypass

: To determine the utility of selective use of venovenous bypass (VVB), an algorithm based upon hemodynamic criteria was instituted at Stanford University Medical Center: the bypass was used if the systolic blood pressure decreased below 100 mm Hg with a trial of caval and portal clamping. : Eleven consecutive patients underwent orthotopic liver transplantation (OLT) with use of VVB on a selective basis; using the hemodynamic exclusion criteria, none required VVB. A group of 20 patients undergoing OLT with VVB served as historical controls. : Overall patient and graft survival were identical in both groups (75%). Avoidance of VVB decreased operative and warm ischemia time and decreased peak transaminase and total bilirubin values, but increased rates of intraoperative blood loss. However, the absolute numbers of blood products administered were not different between groups. : Selective use of VVB for OLT does not incur increased morbidity or mortality. Potential advantages include cost savings with decreased operative and anesthetic time.     

Does adult liver transplantation without venovenous bypass result in renal failure?

Thirty-eight adult orthotopic liver transplant recipients were studied to compare renal hemodynamics and renal function with (17 patients) and without (21 patients) venovenous bypass. Bypass was used when mean arterial blood pressure decreased by greater than 30% or cardiac index decreased by greater than 50%, or both, during a 5-min trial of clamping of the suprahepatic and infrahepatic vena cava and portal vein. Intraoperative measurements were performed 2 h after induction of anesthesia, 10 min before the end of the anhepatic phase, and 2 h after cava unclamping. During the anhepatic stage, renal perfusion pressure decreased significantly in the group with no bypass (79 +/- 20 vs 60 +/- 17 mm Hg, P less than 0.05) (mean +/- SD), whereas it remained unchanged in the group with bypass (77 +/- 14 vs 74 +/- 16 mm Hg, NS); urinary output was not modified in the bypass group, whereas it decreased significantly in the group with no bypass compared with the dissection phase (0.7 +/- 0.6 vs 1.7 +/- 2.0 mL.kg-1.h-1, P less than 0.05). However, during the postreperfusion phase, urinary output was similar in both groups and was more when compared with the dissection phase (P less than 0.05). Serum creatinine level was increased in both groups on the third postoperative day, but no difference occurred between the groups (bypass group 107 +/- 49 mmol/L; nonbypass group 126 +/- 95 mmol/L). No patient required dialysis in either group in the postoperative period. This study suggests that in patients without preoperative renal failure and who tolerate the trial of clamping well, venovenous bypass is not required to maintain postoperative renal function after liver transplantation.