The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.
y Both the authors contributed equally.We compared cold static with acellular normothermic ex vivo liver perfusion (NEVLP) as a novel preservation technique in a pig model of DCD liver injury. DCD livers (60 min warm ischemia) were cold stored for 4 h, or treated with 4 h cold storage plus 8 h NEVLP. First, the livers were reperfused with diluted blood as a model of transplantation. Liver injury was determined by ALT, oxygen extraction, histology, bile content analysis and hepatic artery (HA) angiography. Second, AST levels and bile production were assessed after DCD liver transplantation. Cold stored versus NEVLP grafts had higher ALT levels (350 AE 125 vs. 55 AE 35 U/L; p < 0.0001), decreased oxygen extraction (250 AE 65 mmHg vs. 410 AE 58 mmHg, p < 0.01) and increased hepatocyte necrosis (45% vs. 10%, p ¼ 0.01). Levels of bilirubin, phospholipids and bile salts were fivefold decreased, while LDH was sixfold higher in cold stored versus NEVLP grafts. HA perfusion was decreased (twofold), and bile duct necrosis was increased (100% vs. 5%, p < 0.0001) in cold stored versus NEVLP livers. Following transplantation, mean serum AST level was higher in the cold stored versus NEVLP group (1809 AE 205 U/L vs. 524 AE 187 U/L, p < 0.05), with similar bile production (2.5 AE 1.2 cc/h vs.2.8 AE 1.4 cc/h; p ¼ 0.2). NEVLP improved HA perfusion and decreased markers of liver duct injury in DCD grafts.
An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33 C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n 5 5 for each group). Liver grafts were stored for 10 hours at 4 C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P 5 0.13). No difference was observed between SNEVLP-and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 3 10 24 6 2.6 3 10 24 cells/lm 2 ) but not in CS-treated livers (3.7 3 10 24 6 1.3 3 10 24 cells/lm 2 , P 5 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 6 10 versus 60 6 18 lmol/L, P 5 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P 5 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation.
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