Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation – a randomized clinical trial

Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.     

Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation

Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n = 19) versus CPAr (group 2; n = 21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P = .83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P < .001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P = .0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P = .29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P = .78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P = .01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.     

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults

The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics. A consecutive series (1994-2000) of 167 adult primary OLT were analysed. Ninety-six patients had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim). One-, 3- and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p = ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p = ns). Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups. The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB-ES group there seems to be no advantage for any of the revascularization protocols.     

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.     

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.     

Sequence of reperfusion influences ischemia/reperfusion injury and primary graft function following porcine liver transplantation.

The impact of 3 different reperfusion sequences following orthotopic liver transplantation (OLT) in pigs were evaluated. The reperfusion technique commonly performed is primary portal in order to shorten warm ischemic times (WITs). Experimental and clinical data, usually comparing 2 out of 3 possible reperfusion sequences, provide controversial results. OLT was performed in 24 pigs randomized into 3 groups: primary arterial (A), simultaneous (SIM), and primary portal (P) reperfusion. Hemodynamics were continuously monitored and reperfusion injury and primary graft function were assessed by standard serum parameters, histopathological findings, immunohistochemistry for heme oxygenase 1 (HO-1), and heat shock protein 70 (HSP 70). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (gammaGT) following reperfusion were significantly increased for group A when compared to groups SIM and P. Hemodynamics showed significant differences after reperfusion compared to physiological data; differences in group comparisons were not significant. The bile production/100 g liver/hr was significantly higher for group SIM (1.15 mL) compared to group P (0.66 mL) and group A (0.62 mL). Histology and immunohistochemistry significantly correlated with functional results and outcome. Histological score was best for group SIM and worst for group A. HSP 70, being visualized mainly in the hepatocytes, showed higher expression for groups SIM and P. Inversely, HO-1, found in perisinusoidal cells, showed highest expression after primary arterial reperfusion. In conclusion, although associated with a 10-minute longer warm ischemic time, simultaneous reperfusion causes the least reperfusion injury with superior primary transplant function. Primary arterial reperfusion showed the worst overall outcome and highest degree of HO-1 expression.     

Successful minimally invasive management of late portal vein thrombosis after splenectomy due to splenic artery steal syndrome following liver transplantation: a case report

Portal vein thrombosis (PVT) after liver transplantation (OLT), which occurs in 1% to 2.7% of cases, can compromise patient and graft survival. Percutaneous transhepatic portal vein angioplasty offers an option to treat PVT, diminishing surgically related morbidity and the need for retransplantation. We describe a case of late PVT after OLT, which was successfully treated by a minimally invasive percutaneous transhepatic approach using both mechanical fragmentation and pharmacologic lysis of the thrombus followed by anticoagulation. The patient has had a good clinical course with normal graft function and patent portal blood flow at 6-month follow-up. This case report confirms the possibility of successful recanalization of the portal vein in a patient with late PVT after liver transplantation. Sustained anticoagulation/antiaggregation therapy for at least 6 months after the procedure is advisable.     

Portocaval shunt throughout anhepatic phase in orthotopic liver transplantation for cirrhotic patients

The aim of this study was to assess whether the use of a temporary portocaval shunt (PCS) with inferior vena caval (IVC) preservation during orthotopic liver transplant procedures (OLT) in cirrhotic patients had any advantage. This work evaluated a group of cirrhotic patients who underwent liver-transplant between 1999 and 2006 with a temporary portocaval anastomosis and IVC preservation (PC group, n = 356) versus an historical group (no-PC group, n = 45) with only IVC preservation. We excluded cases of fulminant hepatitis, retransplants, portal vein thrombosis, or prior surgical portosystemic shunts. In both groups, graft reperfusion was achieved by simultaneous arterial and venous revascularization. Donor, recipient, and surgical characteristics were similar in both groups. The PCS group displayed significantly higher portovenous flow (PVF) than the no-PCS group (773 ± 402 mL/min vs 555 ± 379 mL/min, P = .004). We studied two subgroups: high PVF subgroup A (>800 mL/min; mean 1099 ± 261 mL/min) and a low PVF subgroup B (<800 mL/min; mean 433 ± 423 mL/min). In the high flow group (subgroup A) with PCS, a smaller number of blood units were required and better renal function was exhibited at the third postoperatory day. In contrast, no differences were observed among subgroup B between patients with or without PCS. The use of PCS with IVC preservation during the OLT enhanced the hemodynamic recipient status requiring a smaller number of blood units and displaying better renal function.     

Outcome of extra-anatomic vascular reconstruction in orthotopic liver transplantation

BACKGROUND: Portal venous and hepatic arterial reconstruction are critical to successful outcomes in orthotopic liver transplantation (OLT). With portal vein thrombosis or inadequate hepatic arterial inflow, extra-anatomic vascular reconstruction is required. However, the clinical outcomes following extra-anatomic vascular reconstruction are largely unknown. METHODS: To determine the outcomes associated with extra-anatomic vascular reconstruction, we performed a retrospective review of 205 OLT recipients transplanted between 1995 and 2000. RESULTS: Extra-anatomic portal venous inflow was based upon the recipient superior mesenteric vein using donor iliac vein graft in a retrogastric position (n = 12). Extra-anatomic arterial inflow was based on recipient infrarenal aorta using donor iliac artery graft through the transverse mesocolon (n = 25). OLT with routine anatomic vascular construction served as control (n = 168). Extra-anatomic vascular reconstruction was not associated with increased morbidity, mortality, operating room time, length of stay, or thrombosis. CONCLUSION: We conclude that extra-anatomic vascular conduits are associated with excellent long-term outcomes and provide acceptable alternatives for vascular reconstruction in OLT.     

Association between anatomopathologic graft disorders during reperfusion and vena cava sIL-2r in orthotopic liver transplantation

Graft ischemia-reperfusion injury during orthotopic liver transplantation (OLT) is associated with anatomic and pathologic disorders in the graft, which may cause initial dysfunction. The object of this paper was to evaluate sIL-2r as an indicator of liver damage during graft reperfusion.MATERIAL AND METHODS: Blood samples were drawn from 20 consecutive patients who required OLT secondary to chronic end-stage insufficiency various sites (portal vein, vena cava, pulmonary artery) and during different surgical phases. Following centrifugation and storage at -70 degrees C, sIL-2r was quantitated by chemiluminescence (Immulite, EURO/DPC). In addition biopsies were graded from 0 to III according to the anatomic and pathologic findings. Base excess and ammonia were measured to evaluate the function of the new liver. STATISTICAL ANALYSES: Parameter associations were explored using Spearman's Rho and Kendall's Tau-b methods. RESULTS: There was a correlation between the degree of graft preservation and sIL-2R both during vena cava reperfusion (r=.0591, P=.05) and for the initial 2 hours after reperfusion (r=0.61, P=.062). CONCLUSION: sIL-2r levels drawn from the vena cava after graft reperfusion are associated with its degree of injury.     

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.     

间充质干细胞移植对大鼠移植肝脏缺血再灌注损伤的影响

目的 研究骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植促进大鼠减体积肝移植术后肝脏缺血再灌注损伤修复及再生的作用.方法 本研究①取同龄健康Wistar大鼠骨髓进行BMSCs体外培养,用第3代细胞制备悬液.②建立同龄健康Wistar大鼠50%减体积肝移植模型,分为实验组(BMSCs经门静脉植入)和对照组(生理盐水经门静脉注射)观察大鼠术后生存状态,术后不同时间留取血清和肝组织标本,采用免疫组化、流式细胞等方法进行检测.结果 成功体外分离培养BMSCs和建立50%减体积肝移植模型;大鼠肝移植术后2 h,自由活动和饮水.实验组丙二醛(MDA)、超氧化物歧化酶(SOD)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)不同时间点与相应的对照组相比差异有统计学意义(均P＜0.05).实验组细胞周期:术后第2、3天时肝组织的G0/G1期细胞比例显著低于对照组(分别F=22.061,44.572,均P＜0.01).增殖细胞核抗原(PCNA)阳性细胞数增高,术后第2、3和7天时比较,差异有统计学意义(分别F=30.716,28.281,8.975,均P＜0.05).结论 移植肝局部植入BMSCs后,可以促进大鼠肝细胞增殖和加快减体积肝移植术后缺血再灌注损伤的修复.     

Excessive portal flow causes graft nonfunction in small size liver transplantation: an experimental study in pigs

We investigated the effects of portocaval shunt (PCS) on excessive portal flow in producing sinusoidal microcirculatory injury in small-for-size liver transplants in pigs. The posterior segment of a whole liver (25%) was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS (n = 11), and group B, graft without PCS (n = 11). The PCS was a side-to-side anastomosis of the portal vein and the inferior vena cava. In group A, eight pigs survived for more than 4 days; all pigs except for one died of graft nonfunction within 24 hours in group B. The portal flow after reperfusion decreased in group A, but increased about three times greater in group B than that before the operation (P < .01). In group B, destruction of the sinusoidal lining and bleeding in the periportal areas were observed after reperfusion, findings that were not recognized in group A. These results suggest that graft nonfunction after small-for-size liver transplantation may be attributable to excessive portal flow producing sinusoidal microcirculatory injury.     

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.     

Liver Transplantation Using University of Wisconsin or Celsior Preserving Solutions in the Portal Vein and Euro-Collins in the Aorta

Introduction

Orthotopic liver transplantation (OLT) is today the gold standard treatment of the end-stage liver disease. Different solutions are used for graft preservation. Our objective was to compare the results of cadaveric donor OLT, preserved with the University of Wisconsin (UW) or Celsior solutions in the portal vein and Euro-Collins in the aorta.

Methods

We evaluated retrospectively 72 OLT recipients, including 36 with UW solution (group UW) and 36 with Celsior (group CS). Donors were perfused in situ with 1000 mL UW or Celsior in the portal vein of and 3000 mL of Euro-Collins in the aortia and on the back table managed with 500 mL UW or Celsior in the portal vein, 250 mL in the hepatic artery, and 250 mL in the biliary duct. We evaluated the following variables: donor characteristics, recipient features, intraoperative details, reperfusion injury, and steatosis via a biopsy after reperfusion. We noted grafts with primary nonfunction (PNF), initial poor function (IPF), rejection episodes, biliary duct complications, hepatic artery complications, re-OLT, and recipient death in the first year after OLT.

Results

The average age was 33.6 years in the UW group versus 41 years in the CS group (P = .048). There was a longer duration of surgery in the UW group (P = .001). The other recipient characteristics, ischemia-reperfusion injury, steatosis, PNF, IPF, rejection, re-OLT, and recipient survival were not different. Stenosis of the biliary duct occured in 3 (8.3%) cases in the UW group and 8 (22.2%) in the CS (P = .19) with hepatic artery thrombosis in 4 (11.1%) CS versus none in the UW group (P = .11).

Conclusion

Cadaveric donor OLT showed similar results with organs preserved with UW or Celsior in the portal vein and Euro-Collins in the aorta.     

The Effect of Recipient-Specific Surgical Issues on Outcome of Liver Transplantation in Biliary Atresia

Biliary atresia (BA), the most common reason for orthotopic liver transplantation (OLT) in children, is often accompanied by unique and challenging anatomical variations. This study examines the effect of surgical-specific issues related to the presence of complex vascular anatomic variants on the outcome of OLT for BA. The study group comprised 944 patients who were enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry and underwent OLT for BA over an 11-year period. 63 (6.7%) patients met the study definition of complex vascular anomalies (CVA). Patient survival, but not graft survival, was significantly lower in the CVA group, (83 vs. 93 % at 1-year post-OLT). The CVA group had a significantly higher incidence of all reoperations, total biliary tract complications, biliary leaks and bowel perforation. The most frequent cause of death was infection, and death from bacterial infection was more common in the CVA group. Pretransplant portal vein thrombosis and a preduodenal portal vein were significant predictors of patient survival but not graft survival. This study demonstrates that surgical and technical factors have an effect on the outcome of BA patients undergoing OLT. However, OLT in these complex patients is technically achievable with an acceptable patient and graft survival.     

Role of UW solution and sodium nitroprusside in reperfusion of liver xenografts from guinea‐pig to rat

Guinea-pig livers are poorly reperfused when transplanted into rats. We have observed that, in contrast to that of the rat, the guinea-pig intrahepatic portal vein (PV) has a thick layer of smooth muscle. It is possible that, after perfusion of the liver with ice-cold saline, this could go into spasm, resulting in poor reperfusion. To test this hypothesis, guinea-pig livers were perfused with different solutions stored at varying temperatures and transplanted into LEW rats. To prevent xenograft hyperacute rejection, all xenograft recipients were treated with 80 U/kg cobra venom factor (CVF) i.v. on days –1 and 0. In addition to the percentage reperfusion, PV resistance and recipient survival were also monitored. In group I, liver xenografts perfused with ice-cold saline (4°C) reperfused poorly (20–30%), resulting in the development of portal hypertension (16.5 cmH₂O vs. 12 cmH₂O in naive LEW rats) and shortened mean survival time (11.7 ± 4.2 h). In contrast, group II livers perfused with saline at room temperature (23°C) underwent homogeneous reperfusion (98–100%) with no increase in portal vein resistance, indicating that low temperature was the main trigger for the spasm of the PV. Moreover, recipient survival in this group was significantly prolonged to a mean of 22 ± 2.6 h (P < 0.01). Although UW solution (group III) and the vasodilator sodium nitroprusside (NP) (group IV) when used alone improved the degree of hepatic reperfusion, it was still not optimal. The supplementation, however, of UW solution with NP in group V animals resulted in homogeneous reperfusion (98%) with no portal hypertension and consistent prolonged graft survival of 21.0 ± 1.7 h. Therefore, this study has determined that the riddle of the abnormal reperfusion of guinea-pig liver xenografts by rat blood is non-immune mediated and is due to the spasm of the strong smooth muscle in the PV tree produced by cold perfusates.     

Timing of arterialization in liver transplantation.

OBJECTIVE: This study analyzed the pathophysiologic sequela of different modes of graft reperfusion in liver transplantation. SUMMARY BACKGROUND DATA: The grafted liver may be reperfused either immediately after completion of portal anastomosis followed by delayed arterial reconstruction or simultaneously by portal and arterial blood if all vascular anastomoses are completed during the anhepatic period. METHODS: Delayed arterialization, that is, arterial reperfusion 8 minutes after portal revascularization (n = 12), was compared with simultaneous arterialization (n = 8) using the model of syngeneic orthotopic liver transplantation in male Lewis rats. After cold storage for 24 hours in University of Wisconsin (UW) solution, intravital fluorescence microscopy was employed 30 to 90 minutes after reperfusion to assess hepatic microvascular perfusion, leukocyte accumulation, and phagocytic activity of Kupffer cells. RESULTS: Compared with delayed arterialization, the number of both nonperfused acini and nonperfused sinusoids was reduced after simultaneous reperfusion by 71% (p = 0.008) and 78% (p < 0.001), respectively. Leukocyte accumulation in sinusoids and postsinusoidal venules after simultaneous arterialization decreased by 17% (p = 0.01) and 64% (P < 0.001), respectively. In addition, simultaneous revascularization was able to attenuate Kupffer cell activation, indicated by significantly slower adherence of latex beads injected 80 minutes after reperfusion. Improved hepatocellular excretory function after simultaneous arterialization was demonstrated by increased bile flow during the observation period of 90 minutes after reperfusion (2.24 +/- 0.7 vs. 0.95 +/- 0.4 mL/100 g liver [mean +/- SEM], p < 0.05). CONCLUSIONS: Timing of arterial reperfusion in liver transplantation may be of critical importance in the prevention of various manifestations of reperfusion injury.     

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.     

门静脉血栓形成对肝移植手术相关参数的影响

目的 探讨术前合并门静脉血栓(PVT)对原位肝移植(OLT)受者手术和术后相关参数的影响.方法 回顾性分析2002年2月至2007年2月武警总医院836例成人OLT病人中71例术前合并门静脉血栓(PVT组)和765例无门静脉血栓(对照组)病人的临床资料.比较两组手术时间、无肝期时间、输血量等手术参数以及ICU时间、住院时间、PVT复发、移植物功能、门静脉血流量、围手术期病死率和1、3、5年生存率等术后参数.结果 PVT组手术时间(min)和无肝期时间(min)明显长于对照组(分别为792.47±162.29和516.18±186.30,P<0.01;77.53±24.76和48.55±31.20;P<0.05).两组间术中输血量、平均ICU时间、住院时间没有显著差异(P>0.05).PVT组术后再栓塞率显著高于对照组(分别为9.86%和1.44%,P<0.01).除90 d时PVT组门静脉血流(PVF,cm/s)较高(41.43±17.19和19.85±11.39,P<0.05)外,两组间各随访时段移植物功能和PVF没有显著性差异.PVT组围手术期病死率略高于对照组而1、3、5年生存率稍低于对照组,但是差异均没有显著性.结论 术前PVT可能会增加肝移植手术复杂程度,但并不影响肝移植效果.