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Background: Brief normothermic machine perfusion is increasingly used to assess and recondition grafts before transplant. During normothermic machine perfusion, metabolic activity is typically maintained using red blood cell (RBC)-based solutions. However, the utilization of RBCs creates important logistical constraints. This study explored the feasibility of human kidney normothermic perfusion using William's E-based perfusate with no additional oxygen carrier., Methods: Sixteen human kidneys declined for transplant were perfused with a perfusion solution containing packed RBCs or William's E medium only for 6 h using a pressure-controlled system. The temperature was set at 37 °C. Renal artery resistance, oxygen extraction, metabolic activity, energy metabolism, and histological features were evaluated., Results: Baseline donor demographics were similar in both groups. Throughout perfusion, kidneys perfused with William's E exhibited improved renal flow ( P  = 0.041) but similar arterial resistance. Lactic acid levels remained higher in kidneys perfused with RBCs during the first 3 h of perfusion but were similar thereafter ( P  = 0.95 at 6 h). Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding oxygen consumption ( P  = 0.41) and reconstitution of ATP tissue concentration ( P  = 0.55). Similarly, nicotinamide adenine dinucleotide levels were preserved during perfusion. There was no evidence of histological damage caused by either perfusate., Conclusions: In human kidneys, William's E medium provides a logistically convenient, off-the-shelf alternative to packed RBCs for up to 6 h of normothermic machine perfusion., Competing Interests: K.U. and H.Y. have provisional patent applications relevant to this study. K.U. serves on the Scientific Advisory Board for Sylvatica Biotech Inc, a company focused on developing high subzero organ preservation technology. All competing interests are managed by the Mass General Brigham in accordance with their conflict of interest policies., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

There continues to be a significant shortage of donor livers for transplantation. One impediment is the discard rate of fatty, or steatotic, livers because of their poor post-transplant function. Steatotic livers are prone to significant ischemia-reperfusion injury (IRI) and data regarding how best to improve the quality of steatotic livers is lacking. Herein, we use normothermic (37°C) machine perfusion in combination with metabolic and lipidomic profiling to elucidate deficiencies in metabolic pathways in steatotic livers, and to inform strategies for improving their function. During perfusion, energy cofactors increased in steatotic livers to a similar extent as non-steatotic livers, but there were significant deficits in anti-oxidant capacity, efficient energy utilization, and lipid metabolism. Steatotic livers appeared to oxidize fatty acids at a higher rate but favored ketone body production rather than energy regeneration via the tricyclic acid cycle. As a result, lactate clearance was slower and transaminase levels were higher in steatotic livers. Lipidomic profiling revealed ω-3 polyunsaturated fatty acids increased in non-steatotic livers to a greater extent than in steatotic livers. The novel use of metabolic and lipidomic profiling during ex situ normothermic machine perfusion has the potential to guide the resuscitation and rehabilitation of steatotic livers for transplantation., Competing Interests: Dr. Uygun is inventor on pending patents relevant to this study (WO/2011/002926; WO/2011/35223) and has a provisional patent application relevant to this study (MGH 22743). Dr. Uygun has a financial interest in Organ Solutions, a company focused on developing organ preservation technology. Dr. Uygun’s interests are managed by the MGH and Partners HealthCare in accordance with their conflict of interest policies. The hemoglobin-based oxygen carrier, Hemopure was kindly provided by HbO2 Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Ex situ machine perfusion is a promising technology to help improve organ viability prior to transplantation. However, preclinical studies using discarded human livers to evaluate therapeutic interventions and optimize perfusion conditions are limited by significant graft heterogeneity. In order to improve the efficacy and reproducibility of future studies, a split-liver perfusion model was developed to allow simultaneous perfusion of left and right lobes, allowing one lobe to serve as a control for the other. Eleven discarded livers were surgically split, and both lobes perfused simultaneously on separate perfusion devices for 3 h at subnormothermic temperatures. Lobar perfusion parameters were also compared with whole livers undergoing perfusion. Similar to whole-liver perfusions, each lobe in the split-liver model exhibited a progressive decrease in arterial resistance and lactate levels throughout perfusion, which were not significantly different between right and left lobes. Split liver lobes also demonstrated comparable energy charge ratios. Ex situ split-liver perfusion is a novel experimental model that allows each graft to act as its own control. This model is particularly well suited for preclinical studies by avoiding the need for large numbers of enrolled livers necessary due to the heterogenous nature of discarded human liver research.

Normothermic machine perfusion presents a novel platform for pretransplant assessment and reconditioning of kidney grafts. Maintaining the metabolic activity of a preserved graft at physiologic levels requires an adequate oxygen supply, typically delivered by crystalloid solutions supplemented with red blood cells. In this study, we explored the feasibility of using a synthetic hemoglobin-based oxygen carrier (HBOC) in human kidney normothermic perfusion. Fourteen discarded human kidneys were perfused for 6 hours at a mean temperature of 37°C using a pressure-controlled system. Kidneys were perfused with a perfusion solution supplemented with either HBOC (n = 7) or packed red blood cells (PRBC) (n = 7) to increase oxygen-carrying capacity. Renal artery resistance, oxygen extraction, metabolic activity, energy stores, and histological features were evaluated. Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding vascular flow (P = .66), oxygen consumption (P = .88), and reconstitution of tissue adenosine triphosphate (P = .057). Lactic acid levels were significantly higher in kidneys perfused with PRBC (P = .007). Histological findings were comparable between groups, and there was no evidence of histological damage caused by the HBOC. This feasibility experiment demonstrates that a HBOC solution can offer a logistically more convenient off-the-shelf alternative to PRBC in normothermic machine perfusion of human kidneys., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Although percutaneous transluminal coronary angioplasty is successful in more than 90% of patients after acute coronary occlusion, overall mortality remains approximately 10% with higher subgroup mortality (i.e., occlusion of the left anterior descending coronary artery, multivessel disease, age older than 70 years, cardiogenic shock) and early recovery of regional wall motion is marginal. This multicenter report shows that controlled surgical reperfusion in patients with acute coronary occlusion reduces overall and subgroup mortality and restores substantial early contractility. In a survey from six institutions, 156 consecutive patients with acute coronary occlusion documented by angiography underwent surgical revascularization with controlled reperfusion using amino acid-enriched blood cardioplegic solution on total vented bypass. Ventricular wall motion was studied by echocardiography or multiple gated acquisition scan on postoperative days 5 to 7 and scored independently (0 = normal, 1 = mild hypokinesia, 2 = severe hypokinesia, 3 = akinesia, 4 = dyskinesia). Results are compared with results in 1203 patients with acute coronary occlusion treated by angioplasty in five reported medical series. Surgically treated patients were revascularized at longer ischemic intervals (6.3 versus 3.9 hours, p < 0.05) and had a greater incidence of left anterior descending occlusion (61% versus 43%, p < 0.05), multivessel disease (42% versus 22%, p < 0.05), and cardiogenic shock (41% versus 10%, p < 0.05), with 12 patients undergoing cardiopulmonary resuscitation en route to the operating room. Surgical results were superior in all categories, with overall mortality reduced from 8.7% after angioplasty to 3.9% after coronary bypass (p < 0.05). All surgical deaths occurred in patients with preoperative cardiogenic shock. Regional wall motion recovered significantly (score < 2) in 131 of 150 (87%) surgically treated patients with an average score of 0.9 +/- 0.8 (normal to mild hypokinesia) despite longer ischemic times.