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The use of hypothermic machine perfusion (HMP) has recently been used to show an improvement in both standard and extended criteria donor liver grafts but creating a more dynamic preservation environment that can be supplemented with a variety of additives to aid in cold temperature metabolism and vasodilatation. Increasing the benefits of HMP, we explore the use of α-tocopherol in reducing inflammatory markers and apoptotic pathways to reduce the incidence of preservation injury. We explored the use of a donation after cardiac death (DCD) rodent model to test the additive benefits of α-tocopherol in HMP. The addition of α-tocopherol reduced the level of alanine aminotransferase (ALT) over the course of reperfusion as well, reduced the levels of inflammatory cytokines within a 90 minute reperfusion biopsy. Further benefit was seen with α-tocopherol through the reduction of the level of caspase 3/7 in the circulation, shown to be a result of the reduction of the levels of Cytochrome C mRNA. Liver perfusion with Vasosol® and HMP could benefit further from the addition of α-tocopherol to existing formulations of Vasosol®., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT)., Methods: We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5., Results: The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score., Conclusion: Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx)., Methods: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP., Results: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP., Outcomes: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months)., Conclusions: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.

Introduction: Cold storage (CS) is the standard preservation technique for liver transplantation (LTx). Hypothermic machine perfusion (HMP) is an alternative preservation technique that provides a continuous supply of substrates and removes waste products. HMP improves early graft function in kidney transplantation, especially for marginal organs: To our knowledge there have been no reports HMP in human LTx. The aim of this study was to develop a reproducible technique for liver HMP prior to initiating a clinical trial., Methods: For the discard protocol, between May 2001 and March 2002, 10 nontransplantable human livers were obtained. We designed a model of atraumatic, centrifugal HMP of the portal vein (PV) and hepatic artery (HA) via donor vascular conduit. Livers were perfused at 3 degrees C to 5 degrees C with Vasosol solution for 5 to 10 hours using a modified Medtronic Portable Bypass System. Perfusion variables (temp, flow, pressure) where recorded every 30 minutes. During the study, we also validated our techniques in an animal model. For the animal protocol; six swine were used as liver donors and randomized to 12 hours of CS in UW (n = 3) or 12 hours of HMP using Vasosol solution (n = 3). LTx was performed in six swine. Animals survived until postoperative day 5., Results: For the discard protocol, mean HMP time was 6.7 +/- 1.8 hours. Target flow was 0.7 mL/g liver/min. PV and HA pressure ranged from 3 to 5 and 12 to 18 mm Hg, respectively. All grafts were maintained at 3 degrees C to 5 degrees C during HMP. For the animal protocol, all recipients had good liver function and survived to postoperative day 5. AST and TBili were similar between CS and HMP., Conclusions: Our method of liver HMP appears to be a safe and reliable method to preserve livers. A clinical trial is now underway to evaluate this technique in human LTx.

Introduction: Novel preservation techniques may diminish ischemia/reperfusion (I/R) injury. Our preservation laboratory has modified Belzer MPS for machine perfusion (MP) with prostaglandin E1 (PGE 1), nitroglycerin (NTG), and polyethylene glycol-superoxide dismutase (PEG-SOD) to attenuate I/R injury. We reviewed our recent experience using this novel formulation (NF) compared with standard perfusates., Results: Between January 1998 and March 2000, 1060 consecutive kidneys were preserved in our laboratory. One hundred forty-eight kidneys (14%) were discarded. Fifty-eight percent of kidneys during this time period underwent MP (n = 532). En bloc kidney pairs were randomly assigned to pulsatile MP using Waters RM3 or MOX-100 perfusion systems using 1 of 3 perfusates; NF (NF; n = 119), Belzer MPS (MPS; n = 201), or Belzer II albumin gluconate (ALB; n = 212) Significant improvements in delayed graft function (DGF) rate were seen with NF versus other perfusates (8% vs 14% vs 19%, respectively; P =.03). At 6 months, graft survival was significantly improved with NF compared with MPS and ALB (96% vs 90% vs 87%, respectively; P =.03). NF also produced a significantly higher percentage of recipients with a serum creatinine level < or = 1.5 mg/dL., Conclusions: Novel modifications of standard MP perfusate improved outcomes after renal transplantation. Preservation-based interventions targeted to ameliorate I/R injury can improve outcomes and may allow expansion of the donor pool., (Copyright 2004 Elsevier Inc.)