Auxiliary liver transplantation with flow-regulated portal vein arterialization offers a successful therapeutic option in acute hepatic failure – investigations in heterotopic auxiliary rat liver transplantation

Heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was proposed in acute hepatic failure (AHF). However, clinical results of PVA are controversial because of lacking standardized flow-regulation. In rats, we examined HALT with flow-regulated PVA in AHF. Group A: HALT with flow-regulated PVA and 85% resection of the native liver to induce AHF [acute experiments (n = 8), killing after 7 days (n = 8) and after 6 weeks (n = 11)]. Group B: 85% liver-resection (n = 10). The average blood-flow in the arterialized portal vein in HALT achieved normal values (1.7 +/- 0.4 ml/min/g liver-weight). After reperfusion, the diameters of the sinusoids (6.4 +/- 0.6 microm), the postsinusoidal venules (31.1 +/- 3.3 microm) and the intersinusoidal distance (17.9+/-0.7 microm) also achieved normal values. The functional sinusoidal density amounted to 335 +/- 48/cm. The 6-week survival was nine of 11 with excellent liver function (Quick's value: 110% +/- 7.8%). The hepatobiliary radioisotope scanning with (99mTc) ethyl hepatic iminodiacetic acid (EHIDA) showed no significant differences between the native livers and grafts. The hepatocellular morphology was regular, apart from low-grade necroses in two grafts. The grafts' sinusoidal endothelial cells did not show any morphological changes. In group B, however, all rats died from AHF within 6 days. HALT with flow-regulated PVA achieved good results regarding microcirculation, morphology and function and can reliably bridge AHF.     

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.     

Competition between native liver and graft in auxiliary liver transplantation in a rat model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were 相似文献   

Improved technique of heterotopic auxiliary rat liver transplantation with portal vein arterialization

BACKGROUND AND AIMS: In acute, potentially reversible hepatic failure, auxiliary liver transplantation is a promising alternative approach. Using the auxiliary partial orthotopic liver transplantation (APOLT) method--the orthotopic implantation of auxiliary segments--most of the technical problems (lack of space for the additional liver mass, the portal vein reconstruction, and the venous outflow) are avoided, but extensive resections of the native liver and the graft are necessary. Erhard described the heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA). Initial clinical results demonstrated that an adequate liver function can be achieved using this technique. We developed and improved a technique of HALT with flow-regulated PVA in the rat to perform further investigations. The aim of this paper is to explain in detail this improved experimental surgical technique. MATERIALS AND METHODS: Liver transplantations were performed in 122 male Lewis rats: After a right nephrectomy, the liver graft, which was reduced to about 30% of the original size, was implanted into the right upper quadrant of the recipient's abdomen. The infrahepatic caval vein was anastomosed end-to-side. The donor's portal vein was completely arterialized to the recipient's right renal artery in stent technique. Using a stent with an internal diameter of 0.3 mm, the flow in the arterialized portal vein was regulated to achieve physiologic parameters. The celiac trunk of the graft was anastomosed to the recipient's aorta, end-to-side. The bile duct was implanted into the duodenum. RESULTS: After improvements of the surgical technique, we achieved a perioperative survival of 90% and a 6-week survival of 80% in the last 112 transplantations. CONCLUSION: We developed a standardized and improved technique, which can be used for experiments of regeneration and inter-liver competition in auxiliary liver transplantation. Furthermore, this technique is suitable for the investigation of the influence of portal vein arterialization and portal hyperperfusion on liver microcirculation, function, and morphology.     

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).     

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

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

Portal vein reconstruction in pediatric liver transplantation from living donors.

OBJECTIVE: The authors analyze the surgical pattern and the underlying rationale for the use of different types of portal vein reconstruction in 110 pediatric patients who underwent partial liver transplantation from living parental donors. SUMMARY BACKGROUND DATA: In partial liver transplantation, standard end-to-end portal vein anastomosis is often difficult because of either size mismatch between the graft and the recipient portal vein or impaired vein quality of the recipient. Alternative surgical anastomosis techniques are necessary. METHODS: In 110 patients age 3 months to 17 years, four different types of portal vein reconstruction were performed. The portal vein of the liver graft was anastomosed end to end (type I); to the branch patch of the left and right portal vein of the recipient (type II); to the confluence of the recipient superior mesenteric vein and the splenic vein (type III); and to a vein graft interposed between the confluence and the liver graft (type IV). Reconstruction patterns were evaluated by their frequency of use among different age groups of recipients, postoperative portal vein blood flow, and postoperative complication rate. RESULTS: The portal vein of the liver graft was anastomosed by reconstruction type I in 32%, II in 24%, III in 14%, and IV 29% of the cases. In children <1 year of age, type I could be performed in only 17% of the cases, whereas 37% received type IV reconstruction. Postoperative Doppler ultrasound (mL/min/100 g liver) showed significantly (p < 0.05) lower portal blood flow after type II (76.6 +/- 8.4) versus type I (110 +/- 14.3), type III (88 +/- 18), and type IV (105 +/- 19.5). Portal vein thrombosis occurred in two cases after type II and in one case after type IV anastomosis. Portal stenosis was encountered in one case after type I reconstruction. Pathologic changes of the recipient native portal vein were found in 27 of 35 investigated cases. CONCLUSION: In living related partial liver transplantation, portal vein anastomosis to the confluence with or without the use of vein grafts is the optimal alternative to end-to-end reconstruction, especially in small children.     

Utilization of Activated Carbon Hemoperfusion to Assist Recovery of Ischemically Damaged Canine Liver Allografts

The sensitivity of liver allografts to even minimal periods of ischemia currently limits the duration of hepatic preservation prior to liver transplantation. This study evaluates the role of activated carbon hemoperfusion (ACH) for assisting the recovery of canine livers ischemically damaged by a 20-min occlusion of the portal vein and hepatic artery prior to organ harvesting. Animals in Group I (n = 5) receiving damaged liver allografts without ACH survived a mean (+/- SD) of 18.0 +/- 13.5 h. One ACH treatment given to recipients immediately after liver transplantation in Group II (n = 5) resulted in improved survival to a mean of 3.8 +/- 2.16 days (p less than 0.05). The best survival was obtained after three ACH treatments in Group III (n = 6) on days 0, 1, and 2 (26.6 +/- 27.1 days) (p less than 0.05). These results indicate that ACH may be helpful in assisting the recovery of ischemically damaged liver allografts after transplantation.     

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

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

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

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

Reconstruction of middle hepatic vein in living donor liver transplantation with modified right lobe graft: a single center experience

Although a right liver graft without the middle hepatic vein (MHV) can cause congestion in the anterior segment, the reconstruction of MHV tributaries and the complex procedure remain controversial. Between November 2006 and October 2007, right liver transplantation without the MHV was performed in 31 cases. A retrospective analysis was conducted on clinical data and two groups were formed: with MHV reconstruction (Group I, n  = 16) and without MHV reconstruction (Group II, n  = 15). We analyzed the serum liver function markers at 3 weeks postoperatively and evaluated vascular flow in the graft and interpositional vein daily by Doppler ultrasonography during the hospital stay and monthly follow-up after discharge. One patient (6.7%) died of liver congestion and acute hepatic rejection on the postoperative day 10 in Group II. Congestion was observed in another three cases (20%) of Group II and one case (6.25%) of Group I. The levels of alanine transferase and aspartate transferase in Group II was higher than those in Group I in the first week after transplantation, albeit not significantly. In Group I, most of the interpositional vein grafts were the recipient's portal veins. Venoplasty in the graft was performed in three cases. All the interpositional veins and tectonic outflow orifices were detected to be patent by ultrasonography within 14 days after transplantation. The reconstruction of the MHV tributaries is necessary in the right liver graft without MHV according to our policy and better criteria for MHV reconstruction should be established. The recipient's portal vein is an optimal choice for the interpositional vein and hepatic venoplasty in living donor liver transplantation can simplify the operation and ensure excellent venous drainage.     

An experimental study on the pathophysiology of stenosis and occlusion in portal vein reconstruction in resection of cancer of the hepatic hilus

An experimental study using mature mongrel dogs was performed to clarify the pathophysiology of stenosis and occlusion of portal vein reconstruction accompanied with hepatectomy. All the animals underwent partial (53%) hepatectomy. They were arbitrarily divided into three groups: Non-stenosis Group I with hepatectomy only, Stenosis Group II with partial '70%) stenosis of the portal vein, and Occlusion Group III with ligation of the portal vein. All cases of Group III died within about 122 minutes. The blood flow and pressure of the portal vein, portography, ICG Rmax and the residual liver weight were serially examined until the fourth week following the operation in Group I and Group II. Two principal results were derived: 1) In Group I, portal circulation was sufficiently restored and the residual liver showed adequate regeneration. 2) In Group II, hepatofugal collateral vessels developed. However, the portal pressure remained significantly high (p less than 0.002) and, the portal blood flow and liver tissue blood flow were markedly reduced (p less than 0.001) for 1 week after operation. The residual liver weight and liver function (ICG Rmax) were significantly decreased even in the fourth week. Recently, portal vein resection accompanied with hepatectomy has been accepted as a procedure for advanced carcinoma of the hepatic hilus. This study suggests that stenosis or occlusion of the portal vein should be avoided in the procedure.     

A model for directed foreign gene delivery to rat liver cells in vivo.

A novel technique for directed delivery of retroviral genes to rat liver cells in vivo is described. Vascular isolation of the liver was achieved in situ and perfusate containing retrovirus expressing the bacterial gene conferring resistance to Hygromycin-B was delivered selectively to the posterior liver lobes. After 15 min, normal blood flow to the liver was restored. The portal venous branch supplying the two anterior liver lobes was ligated either at the same time (Group I, n = 4) or 20 hr prior to perfusion (Group II, n = 4) to stimulate DNA synthesis in the posterior lobes. Controls (Group III, n = 4) were perfused with retrovirus without portal branch ligation. Hepatocyte transduction was assessed 7 days later by isolating the cells and assessing their viability in a selection medium. In Group I and II rats, 9.2 +/- 0.5 and 16.0 +/- 1.0%, respectively, of harvested hepatocytes, expressed the Hygromycin-B gene. In contrast, a significantly smaller number of hepatocytes (2.8 +/- 0.9%, P less than 0.003) expressed the gene in the absence of stimulation of DNA synthesis.     

Auxiliary rat liver transplantation with portal vein arterialization in acute hepatic failure

BACKGROUND: The aim of our work was to study the effect of the portal vein arterialization of an auxiliary liver graft on survival, liver function, and regeneration of the native liver suffering from surgically induced acute liver failure (ALF). METHODS: In Lewis rats (control group: n=10), ALF was induced by resection of about 85% of liver tissue. The auxiliary liver graft (reduced size of 30%) was transplanted into the right upper quadrant of the abdomen (trial group: n=12). The portal vein was arterialized via the renal artery. The infrahepatic vena cava was anastomosed end-to-side, and the bile duct was implanted into the duodenum. RESULTS: Survival rate over a 3-month period was 10/12 in the trial group vs. 2/10 in the controls. In the trial group, the prothrombin time rose up to 38+/-2 sec on day 1 after surgery (control group: 66+/-6 sec); on day 5 after surgery, it returned to values of 30+/-1 sec. On day 1 after surgery, serum albumin fell to 25+/-1 g/L (preoperative value: 32+/-1 g/L). Within 3 weeks, it returned to normal. The hepatobiliary scan on day 7 after surgery showed normal uptake in the liver graft, whereas the uptake of the native liver was distinctly reduced. After 3 months, the transplanted liver had atrophied (0.6% of body weight), the native liver hypertrophied (2.5% of body weight), with a normal total weight for both livers of 3.1% of body weight. CONCLUSIONS: Thus, auxiliary liver transplantation with arterialized portal vein allows maintenance of liver function at the time of ALF and regeneration of the native liver.     

Primary permanent arterialization of the portal vein in liver transplantation

Permanent total arterialization of the portal vein in liver transplantation has been described as a method of providing portal inflow after insufficient thrombectomy due to chronic occlusion of the portal-vein system. A specific problem is the restriction of the arterial inflow and its long-term adaptation after transplantation. We describe here the surgical techniques and clinical course of three patients who underwent portal-vein arterialization for liver transplantation. Two patients had an uneventful course. In one patient, a flow reduction by means of coil embolization of one arterial inflow branch was performed; thereafter, the patient recuperated well. Analysing the microcirculation of an arterialized graft in comparison with liver grafts with normal non-arterialized portal-vein inflow, we observed an increase in inter-sinusoidal distance and a decrease in sinusoidal red blood cell velocity. From a technical point of view, we recommend permanent portal-vein arterialization by an iliac artery graft interposition from the subdiaphragmatic aorta. The inflow to the portal vein can easily be reduced by the banding of the arterial graft interposition.     

Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model

Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/- 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings.     

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

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

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

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

The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat.

This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.