Dual lactate clearance in the viability assessment of livers donated after circulatory death with ex situ normothermic machine perfusion

Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death. Methods: The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (\u3c2.2 mmol/L at 2 h, n = 5, rapid retrieval without normothermic regional perfusion). Results: We found the pERK1/2 level was substantially higher in the nLC livers than in the sLC livers (n = 5) at 2- and 6-h NMP ( Conclusions: The dual LC in perfusate and bile can be helpful in evaluating the hypoxic injury of hepatocytes and cholangiocytes during the NMP of donation after circulatory death in liver donors

Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model

Background. Over 100 000 patients await renal transplantation and 4000 die per year. Compounding this mismatch between supply and demand is delayed graft function which contributes to short-term and long-term graft failures. Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC-NP) protect kidneys from ischemic renal injury after transient arterial occlusion. Here we hypothesize that perfusion of renal allografts with PFC-NP similarly can protect graft function after an ischemic interval. Methods. After 60 minutes of warm ischemia, male Lewis rats underwent left renal explantation followed by renal perfusion with 5 mL of standard perfusate alone (N = 3) or with 0.3 mL of untargeted PFC-NP (N = 5) or 0.3 mL thrombin-targeted of PFC NP functionalized with phenylalanine-proline-arginine-chloromethylketone (PPACK) (PFC-PPACK), an irreversible thrombin inhibitor (N = 5). Kidneys underwent 6 hours of cold storage, followed by transplantation into recipients and native nephrectomy. Animals were euthanized at 24 hours for tissue collection or at 48 hours for blood and renal tissue collection. A survival experiment was performed using the same protocol with saline control (N = 3), PFC-NP (N = 3) or PFC-PPACK (N = 6). Results. Serum creatinine was improved for the PFC-PPACK groups as compared with control groups (P < 0.04). Kaplan-Meier survival curves also indicated increased longevity (P < 0.05). Blinded histologic scoring revealed markedly attenuated renal damage in the PFC-PPACK group compared to untreated animals (2.75 ± 1.60 versus 0.83 ± 3.89; P = 0.0001) and greater preservation of renal vasculature. Conclusions. These results validate an NP-based approach to improve renal graft function as antithrombin NPs improved allograft function, decreased renal damage, protected vasculature, and improved longevity