Role of donor hemodynamic trajectory in determining graft survival in liver transplantation from donation after circulatory death donors.

Donation after circulatory death (DCD) donors show heterogeneous hemodynamic trajectories following withdrawal of life support. Impact of hemodynamics in DCD liver transplant is unclear, and objective measures of graft viability would ease transplant surgeon decision making and inform safe expansion of the donor organ pool. This retrospective study tested whether hemodynamic trajectories were associated with transplant outcomes in DCD liver transplantation (n = 87). Using longitudinal clustering statistical techniques, we phenotyped DCD donors based on hemodynamic trajectory for both mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2 ) following withdrawal of life support. Donors were categorized into 3 clusters: those who gradually decline after withdrawal of life support (cluster 1), those who maintain stable hemodynamics followed by rapid decline (cluster 2), and those who decline rapidly (cluster 3). Clustering outputs were used to compare characteristics and transplant outcomes. Cox proportional hazards modeling revealed hepatocellular carcinoma (hazard ratio [HR] = 2.53; P = 0.047), cold ischemia time (HR = 1.50 per hour; P = 0.027), and MAP cluster 1 were associated with increased risk of graft loss (HR = 3.13; P = 0.021), but not SpO2 cluster (P = 0.172) or donor warm ischemia time (DWIT; P = 0.154). Despite longer DWIT, MAP and SpO2 clusters 2 showed similar graft survival to MAP and SpO2 clusters 3, respectively. In conclusion, despite heterogeneity in hemodynamic trajectories, DCD donors can be categorized into 3 clinically meaningful subgroups that help predict graft prognosis. Further studies should confirm the utility of liver grafts from cluster 2. Liver Transplantation 22 1469-1481 2016 AASLD.

Split liver transplantation in adults.

Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

Impact of donor age in liver transplantation from donation after circulatory death donors: A decade of experience at Cleveland Clinic.

The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation.

A Structured Educational Curriculum Including Online Training Positively Impacts American Board of Surgery In-Training Examination Scores.

OBJECTIVE: To assess the effect of a structured postgraduate year 1 educational curriculum, including online surgical training, on American Board of Surgery In-Training Examination (ABSITE) scores. DESIGN: This was a retrospective cohort study. SETTING: The study was performed in an academic surgical residency program in a tertiary care hospital, Cleveland Clinic Foundation, Cleveland, Ohio. PARTICIPANTS: The participants were 140 surgical postgraduate year 1 residents from 2000 to 2009. Interns from 2000 to 2004 were grouped together and completed a self-directed learning curriculum. Interns from 2005 to 2009 participated in a structured educational curriculum that included lectures and the use of an online program. Lectures were based on the American College of Surgeons curriculum. The online program consisted of 8 to 12 hours of assigned tutorials and quizzes that corresponded to the lectures and 3 multiple-choice (MC) examinations. RESULTS: Use of a structured educational curriculum led to improved ABSITE scores (66 ± 9%) compared with that of those who had no curriculum (55 ± 10%, p < 0.001). Several variables positively correlated with the ABSITE score: United States Medical Licensing Examination step 1 score (p < 0.001), monthly quiz scores (p = 0.003), average MC examination scores (p = 0.005), lecture attendance (p = 0.02), and time spent online (p = 0.04). Multivariable analysis demonstrated that the step 1 United States Medical Licensing Examination score, time spent online, and MC examination score are predictive of total the ABSITE score. When ABSITE subscores (basic science and clinical science) were compared, the online curriculum had a greater effect on basic science subscores, whereas lectures had a greater effect on clinical science subscores. CONCLUSIONS: Providing surgery residents a structured curriculum with lectures and an online component positively impacts ABSITE scores.

Oxygen consumption predicts outcome in porcine partial liver grafts.

BACKGROUND: High oxygen consumption (OC) in recipients of cadaveric whole liver grafts is associated with a poor prognosis. The aim of this study is to investigate the relationship between intraoperative hepatic OC and graft function and survival in a porcine partial liver graft model. MATERIAL AND METHODS: Experiments followed the Guiding Principles in the Care and Use of Laboratory Animals. Fourteen female pigs, 46-69 kg, received liver allografts of 17%-39% liver volume and were followed for 14 d. We measured donor and recipient body weights, percentage graft weight and expressed it as a percentage of standard liver volume, cold ischemia time, hepatic artery flow (HAF), portal vein flow (PVF), graft volume at sacrifice, serum lactate, prothrombin time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, albumin, total protein, alkaline phosphatase, total bilirubin, and recipient survival. OC was calculated as follows: OC (mL/100 g/min) = ([Hemoglobin {Hb} × 1.34 × SaO2 + 0.003 × PaO2] × HAF + [Hb × 1.34 × SpO2 + 0.003 × PpO2] × PVF - [Hb × 1.34 × SvO2 + 0.003 × PvO2] × [HAF + PVF])/graft weight (100 g), and animals were divided into two groups: low OC group (OC < 2.0 mL/100 g/min) and high OC group (OC ≥ 2.0 mL/100 g/min). RESULTS: In survival analysis, four of seven low OC recipients (57% [n = 7]) survived until the end of the study period compared with one of seven high OC recipients (14% [n = 7]). The low OC group had a significantly higher survival rate than that of the high OC group (P = 0.041). Low OC was associated with higher HAF (mL/100 g/min) after reperfusion compared with that of the high OC group, 29.0 ± 13.8 versus 16.0 ± 11.1 mean ± standard deviation; P = 0.073. Serum alkaline phosphatase and total bilirubin in the low OC group were significantly better than those of the high OC group. Serum lactate was comparable in both groups. Graft weight at the time of sacrifice in the low OC group tended to be higher than that in the high OC group, but not significantly (P = 0.097). CONCLUSIONS: High intraoperative OC is associated with lower HAF, decreased graft function, and decreased survival in the porcine partial liver graft model.

Predicting the discharge status after liver transplantation at a single center: a new approach for a new era.

The aim of this study was to develop a tool for preoperatively predicting the need of a patient to attend an extended care facility after orthotopic liver transplantation (OLT). A multidisciplinary group, which included 2 transplant surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case manager, 1 home health care professional, 1 rehabilitation physician, and 1 statistician, met to identify preoperative factors relevant to discharge planning. The parameters that were examined as potential predictors of the discharge status were as follows: age, sex, language, Karnofsky score, OLT alone (versus a combined procedure), creatinine, bilirubin, international normalized ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical Model for End-Stage Liver Disease score, renal dialysis, location before transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and right ventricular systolic pressure, sex and availability of the primary caregiver, donor risk index, and donor characteristics. Between January 2004 and April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and 47 patients (6%) underwent combined procedures. Five hundred nineteen patients (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%) died early after OLT. A multivariate logistic regression analysis identified the following parameters as significantly influencing the discharge status: a low Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of 2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI, and renal dialysis before OLT. The nomogram was prospectively validated with a population of 126 OLT recipients with a concordance index of 0.813. In conclusion, a new approach to improving the efficiency of hospital care is essential. We believe that this tool will aid in reducing lengths of stay and improving the experience of patients by facilitating early discharge planning.

The role of the A2a receptor agonist, regadenoson, in modulating hepatic artery flow in the porcine small-for-size liver graft.

BACKGROUND: Hepatic artery vasoconstriction plays a major role in the pathophysiology of the small-for-size (SFS) liver graft injury and is reversed by adenosine. The A2a adenosine receptor (AR) has been suggested to be one of the key receptors that modulate hepatic hemodynamic changes. The aim of the study is to define the effects of the A2a AR agonist, regadenoson, in modulating hepatic artery flow (HAF) in SFS liver grafts of a porcine model. METHODS: Seven female recipient pigs (66-70 kg) receiving 20% liver grafts were treated with regadenoson, 0.1 ug/kg/min starting on POD1 (n = 7). Results were compared with those with untreated 20% liver grafts (n= 8). The recipients were observed for 14 d. Hepatic artery flow (HAF) and portal vein flow (PVF) were recorded. Liver biopsies and serum samples were also taken at the designed time points through postoperative day (POD)14. RESULTS: Dose-response curves of regadenoson established 0.1 ug/kg/min as the most effective dose of regadenoson for maintaining an increase in HAF. No adverse effects were seen with regadenoson infusion. HAF immediately increased by up to 2.2-fold after regadenoson infusion. The levels of daily average of HAF and percentage of HAF in total liver blood flow were 34.5% and 41.8%, respectively, higher in the regadenoson group than in the untreated group. Histologic scores of hepatic artery spasm and bile duct necrosis were significantly lower in the regadenoson group than in the untreated group (P = 0.01 and 0.04, respectively). The complication rates of hepatic artery thrombosis and gastrointestinal bleeding were lower in the regadenoson group than in the untreated group (0/7, 0% versus 2/8, 25% and 0/7, 0% versus 2/8 and 25%, respectively). The 14-d survival rates were 4/7 (57.1 %) in regadenoson group compared with 2/8 (25%) in the untreated group. CONCLUSION: Adenosine A2a AR agonist, regadenoson, increases HAF in the recipients of SFS grafts with modest improvements in outcome.

Elevated catecholamines and hepatic artery vasospasm in porcine small-for-size liver graft.

BACKGROUND: Elevated levels of norepinephrine (NE) have been reported in recipients of small-for-size liver (SFS) grafts in the perioperative period. The aim of the study is to test the hypothesis that although circulating catecholamines are elevated in recipients of SFS grafts, they are not the primary agents responsible for the hepatic artery (HA) vasospasm. METHODS: Female porcine recipients receiving a 20% (n = 10) partial liver graft were compared with a control group, using 60% partial liver transplanted grafts (n = 9). Hepatic blood flow (PVF, HAF) and levels of plasma catecholamines (epinephrine and NE) were measured at designated time points through postoperative day (POD) 7. Phentolamine (PA), an α-adrenergic blocker, was administered at doses of 1 to 112.5 ug/kg/min through an indwelling HA to the recipients of 20% group on POD1 (n = 5). RESULTS: In the 20% group following reperfusion, HA vasospasm was found at 10, 60, and 90 min, and persisted on POD 3 and POD 7. Plasma NE levels increased after reperfusion in 20% and 60% groups and peaked at 6 h with 10- to 13-fold increased levels compared with baseline. In the 20% group, NE levels remained elevated up to POD 7. PA infusion at low (1-10 ug/kg/min) and high (12.5-112.5 ug/kg/min) doses did not reverse the reduced HAF observed in 20% group recipients. CONCLUSION: Elevated serum NE does not appear to be the primary factor mediating HA vasospasm in the porcine SFS graft.

Hepatic blood flow plays an important role in ischemia-reperfusion injury.

Severe ischemia/reperfusion (IR) injury is associated with poor hepatic microperfusion. The aim of this study was to investigate the role of hepatic artery flow (HAF) and portal vein flow (PVF) in IR injury. From January 2004 to June 2008, 566 patients underwent orthotopic liver transplantation (OLT). The data were retrospectively reviewed via the transplant database. Patients with hepatic artery (HA) or portal vein (PV) thrombosis and retransplant patients were excluded. Intraoperative PVF and HAF values and graft weights were measured routinely, and the central venous pressure, mean arterial pressure, cardiac output, and cardiac index were recorded with hepatic blood flow measurements. Complete data were available for 312 primary OLT recipients (215 males and 97 females; mean age = 54 ± 10 years). The patients' follow-up ranged from 215 to 1746 days (705 ± 408 days). IR injury was defined by the aspartate aminotransferase (AST) level on postoperative day (POD) 2, and the patients were divided into 3 groups: (1) mild IR injury [AST < 500 U/L; n = 160 (51%)], (2) moderate IR injury [AST = 500-1000 U/L; n = 85 (27%)], and (3) severe IR injury [AST > 1000 U/L; n = 67 (21%)]. The demographics and pre-OLT variables (the Model for End-Stage Liver Disease score (MELD), platelet counts, PV thrombosis, transjugular intrahepatic portosystemic shunts, and shunts on computed tomography scans) were similar in all groups. The graft survival rate was 99% in group 1, 95.2% in group 2 (P = 0.02), and 92.3% in group 3 (P = 0.016). The patient survival rates were similar in the 3 groups. The cold ischemia time (CIT) was significantly higher in group 3 versus group 1 (P < 0.007). In the statistical analysis, low HAF, PVF, total liver blood flow (TLBF), and augmented HAF values were associated with a greater likelihood of elevated AST levels on POD 2. The strongest univariate predictors of AST were reduced augmented HAF (mL/minute/100 g) values (P < 0.001) and reduced TLBF (mL/minute/100 g) values (P < 0.001). In a covariate analysis with adjustments for CIT and donor variables, the blood flow parameters remained important predictors of graft function. In conclusion, this report demonstrates for the first time that reduced hepatic blood flow is a significant finding in patients with severe hepatic IR injury.

Splenic artery embolization for the treatment of refractory ascites after liver transplantation.

Refractory ascites (RA) is a challenging complication after orthotopic liver transplantation. Its treatment consists of the removal of the precipitating factors. When the etiology is unknown, supportive treatment can be attempted. In severe cases, transjugular intrahepatic portosystemic shunts, portocaval shunts, and liver retransplantation have been used with marginal results. Recently, splenic artery embolization (SAE) has been described as an effective procedure for reducing portal hyperperfusion in patients undergoing partial or whole liver transplantation. Here we describe our experience with SAE for the treatment of RA. Between June 2004 and June 2010, 6 patients underwent proximal SAE for RA. Intraoperative flow measurements, graft characteristics, embolization portal vein (PV) velocities before and after SAE, and spleen/liver volume ratios were collected and analyzed. The response to treatment was assessed with imaging (ultrasound/computed tomography) and on the basis of clinical outcomes (weight changes, diuretic requirements, and the time to ascites resolution). The PV velocity decreased significantly for each patient after the embolization (median = 66.5 cm/second before SAE and median = 27.5 cm/second after SAE, P < 0.01). All patients experienced a significant postprocedural weight loss (mean = 88.1 ± 28.4 kg before SAE and mean = 75.8 ± 28.4 kg after SAE, P < 0.01) and a dramatic decrease in their diuretic requirements. All but 1 of the patients experienced a complete resolution of ascites after a median time of 49.5 days (range = 12-295 days). No patient presented with postembolization complications. In conclusion, SAE was effective in reducing the PV velocity immediately after the procedure. Clinically, this translated into a dramatic weight loss, a reduction of diuretic use, and a resolution of ascites. SAE appears to be a safe and effective treatment for RA.

Glucose balance of porcine liver allograft is an important predictor of outcome.

BACKGROUND: The role of glucose metabolism in predicting postoperative liver graft function after transplantation is unclear. We investigated the relation between intraoperative glucose balance of the liver allograft and the postoperative graft function and survival in a porcine partial liver transplant model. MATERIALS AND METHODS: Experiments follow Guiding Principles in the Care and Use of Animals. Fourteen female pigs received liver allografts of 17%-39% recipient liver volume. Recipients were classified into two groups based on positive glucose balance: the mean intraoperative blood glucose of the graft outflow was greater than the blood glucose of inflow, negative glucose balance: the mean blood glucose of graft outflow was less than blood glucose of inflow. Perioperative data and survival were studied. RESULTS: In the positive group (n=9) intraoperative hepatic artery flow was significantly higher (P=0.028), and oxygen consumption was lower (P=0.018) than the negative group (n=5). Postoperatively, maximal serum aspartate aminotransferase (AST) (P=0.028), alanine aminotransferase (ALT) (P=0.028), and total bilirubin (P=0.027) of the positive group were significantly lower than the negative group. In survival analysis, the positive group had significantly better survival rate than the negative group (P=0.034). Using Periodic acid-Schiff staining, glycogen content of the allograft in the positive group at 10 min post-reperfusion was significantly decreased in comparison with the baseline value in the normal liver (P=0.005), however not statistically different in the negative group (P=0.175). CONCLUSION: Intraoperative glucose balance can be used as an early predictor of the graft function following transplantation of partial liver allografts.

Is impaired hepatic arterial buffer response a risk factor for biliary anastomotic stricture in liver transplant recipients?

BACKGROUND: Blood flow to the liver is partly maintained by the hepatic arterial buffer response (HABR), which is an intrinsic autoregulatory mechanism. Temporary clamping of the portal vein (PV) results in augmentation in hepatic artery flow (augHAF). Portal hyperperfusion impairs HAF due to the HABR in liver transplantation (LT). The aim of this study is to examine the effect of the HABR on biliary anastomotic stricture (BAS). METHODS: In 234 cadaveric whole LTs, PV flow (PVF), basal HAF, and augHAF were measured intra-operatively after allograft implantation. All recipients with a vascular complication were excluded. Buffer capacity (BC) was calculated as (augHAF - basal HAF)/PVF to quantify the HABR. Recipients were divided into 2 groups based on their BC: low BC (<0.074; n = 117) or high BC (> or =0.074; n = 117). RESULTS: Of the 234 recipients, 23 (9.8%) had early BAS (< or =60 days after LT) and 18 (7.7%) had late BAS (>60 days after LT). The incidence of late BAS and bile leakage was similar between the groups; however, the incidence of early BAS in the low BC group was greater than that in the high BC group (15% vs 5.1%; P = .0168). In the multivariate analysis, low BC (P = .0325) and bile leakage (P = .0002) were found to be independent risk factors affecting early BAS. CONCLUSION: Recipients with low BC who may have impaired HABR are at greater risk of early BAS after LT. Intraoperative measurements of blood flow help predict the risk of BAS.

Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome.

The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100 g/min) were 29 +/- 12 (mean +/- SD) and 74 +/- 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7-14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 +/- 8 ml/100 g/min at 90 min and remained low out to POD 7-14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome.

Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome.

In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; 13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.3 (range 0.6 to 1.4), were transplanted without complications, initially, into 6 relatively healthy 25 to 63-year-old recipients. However, all recipients developed otherwise unexplained jaundice, coagulopathy, and ascites within 5 days after transplantation. Examination of sequential posttransplant biopsies and 3 failed allografts with clinicopathologic correlation was used in an attempt to reconstruct the sequence of events. Early findings included: (1) portal hyperperfusion resulting in portal vein and periportal sinusoidal endothelial denudation and focal hemorrhage into the portal tract connective tissue, which dissected into the periportal hepatic parenchyma when severe; and (2) poor hepatic arterial flow and vasospasm, which in severe cases, led to functional dearterialization, ischemic cholangitis, and parenchymal infarcts. Late sequelae in grafts surviving the initial events included small portal vein branch thrombosis with occasional luminal obliteration or recanalization, nodular regenerative hyperplasia, and biliary strictures. These findings suggest that portal hyperperfusion, venous pathology, and the arterial buffer response importantly contribute to early and late clinical and histopathologic manifestations of the small-for-size syndrome.

Porcine partial liver transplantation: a novel model of the "small-for-size" liver graft.

Increasing shortage of cadaveric grafts demands the utilization of living donor and split liver grafts. The purpose of this study was to 1) define the "small-for-size" graft in a pig liver transplant model 2) evaluate pathological changes associated with small-for-size liver transplantation. Pigs were divided into four groups based on the volume of transplanted liver: (a) control group (n=4), 100% liver volume (LV) (b) group I (n=8), 60% LV (c) group II (n=8), 30% LV (d) group III (n=15), 20% LV. Tacrolimus and methyl prednisone were administered as immunosuppression. Animals were followed for 5 days with daily serum biochemistry, liver biopsies on day 3 and 5 for light microscopy, and tissue levels of thymidine kinase (TK) and ornithine decarboxylase (ODC). Liver grafts were weighed pretransplant and at sacrifice. All the recipients of 100%, 60%, and 30% grafts survived. Transplantation of 20% grafts (group III) resulted in a 47% mortality rate. Group III animals showed significantly prolonged prothrombin times (p<0.05), elevated bilirubin levels (p<0.05), and ascites. The rate of regeneration, as indicated by TK activity and graft weight was inversely proportional to the size of the transplanted graft. The severity of the microvascular injury was inversely proportional to graft size and appeared to be the survival-limiting injury. Frank rupture of the sinusoidal lining, parenchymal hemorrhage, and portal vein injury were prominent in group III animals 1 hour following reperfusion. This study established a reproducible large animal model of partial liver grafting; it defined the small-for-size syndrome in this model and described the associated microvascular injury.