Perspectives in organ preservation

Maintaining organ viability after donation until transplantation is critically important for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in every day clinical practice. Although simple and effective, it is questionable whether this method is able to prevent deterioration of organ quality in the present era with increasing numbers of organs retrieved from older, more marginal, and even non-heart-beating donors. This review describes principles involved in effective preservation and focuses on some basic components and methods of abdominal organ preservation in clinical and experimental transplantation. Concepts and developments to reduce ischemia related injury are discussed, including hypothermic machine perfusion. Despite the fact that hypothermic machine perfusion might be superior to static cold storage preservation, organs are still exposed to hypothermia induced damage. Therefore, recently some groups have pointed at the beneficial effects of normothermic machine perfusion as a new perspective in organ preservation and transplantation

Deterioration of Endothelial and Smooth Muscle Cell Function in DCD Kidneys After Static Cold Storage in IGL-1 or UW

Background. Kidneys obtained from donors after cardiac death are damaged by the combination of warm and cold ischemia. Although the parenchymal damage of these kidneys is well studied, little is known about the functional effects of warm and cold ischemia on the renal vascular bed. We compared kidney preservation using the new extracellular-type cold storage solution from Institut Georges Lopez (IGL-1) with the University of Wisconsin solution (UW) and focused on vasomotor functions. Methods. The influence of warm and cold ischemia on vasomotor functions was studied in an isolated perfused kidney model. Six groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0, 15, and 30 min followed by 0 or 24 h cold storage preservation in IGL-1 or UW at 4 degrees C. Endothelial dependent vasodilation was studied using acetylcholine, smooth muscle cell (SMC) constriction was assessed using phenylephrine, and finally endothelial independent relaxation was tested using papaverine-sulfate. Results. SMCs were significantly affected by cold ischemia showing a 50%. reduction of phenylephrine mediated constriction after preservation. Additional warm ischemia did not affect SMCs. After UW preservation endothelial dependent vasodilation was only significantly reduced when the combination of warm and cold ischemia was present. IGL-1 preserved kidneys showed a reduction in endothelial dependent vasodilation after isolated warm ischemia. Both preservation solutions rendered equal results after 24 h preservation. Conclusion. Vasomotor functions are negatively influenced by the combination of warm and cold ischemia. Both IGL-1 and UW performed equally in preserving vasomotor functions. The interesting finding of the rapid decline of SMC function might point at the first step toward intimal hyperplasia as seen in late transplant dysfunction. (C) 2009 Elsevier Inc. All rights reserved

Acute isovolemic hemodilution triggers proinflammatory and procoagulatory endothelial activation in vital organs: Role of erythrocyte aggregation

Objectives: The essential role of erythrocytes as oxygen carriers is historically well established, but their function to aggregate and the consequences on the microcirculation is under debate. The pathogenic potential of low erythrocyte aggregation could be important for patients undergoing on-pump cardipopulmonary bypass. These patients are severely hemodiluted due to preoperative isovolemic hemodilution (IHD), circuit priming, and large fluid infusions perioperatively. Considering the vascular endothelium sensitivity to variations in blood rheology, the authors hypothesize that low erythrocyte aggregation will be responsible for activation of vascular endothelium during acute IHD. Methods: Acute IHD (30 mL/kg exchange transfusion with colloid solutions) was induced in an "aggregating species(pigs, n = 15). The hypoxic oxidative stress (plasma malondialdehyde, ex vivo oxygen radicals production in heart, lung, kidney, liver, and ileum tissue biopsies), erythrocyte aggregation (LORCA), and endothelial activation (real-time quantitative RT-PCR on von Willebrand factor (vWF), E- and P-selectins, endothelial nitric oxide synthase gene-expression in tissue biopsies) were investigated. Results: The production of superoxide and hydroxyl radicals, measured as H2O2 generation, was similar at all times in sham-operated and hemodiluted animals, proving a maintained oxygen delivery to tissues. Acute IHD was followed by a dramatic drop in erythrocyte aggregation and immediate prothrombotic (significant vWF mRNA upregulation in heart, lungs, kidney, liver, ileum) and proinflammatory (significant E- and P-selectins mRNA upregulation in lungs and ileum) endothelial activation. Low erythrocyte aggregation was significantly correlated with increased mRNA-expression of vWF (heart, liver, ileum) and P-selectin (lungs, ileum, and heart). Conclusions: These results suggest that low erythrocyte aggregation might trigger endothelium-dependent thrombogenic and proinflammatory response during acute isovolemic hemodilution

Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death

P>The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart-beating deceased ECDs - defined according to the United Network of Organ Sharing definition - were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362)

Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

BACKGROUND Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. METHODS In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function ( requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. RESULTS Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine- perfusion group versus 89 in the cold- storage group ( adjusted odds ratio, 0.57; P = 0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure ( hazard ratio, 0.52; P = 0.03). One- year allograft survival was superior in the machine- perfusion group ( 94% vs. 90%, P = 0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. CONCLUSIONS Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)