Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Abstract

Controlled oxygenated rewarming (COR) up to 20°C during ex vivo machine perfusion limits reperfusion-induced tissue injury upon graft implantation. Rewarming up to normothermia might add further benefits and provide better prediction of posttransplantation organ function. The effect of 90 minutes of oxygenated machine perfusion with Aqix RS-I after cold storage combined with gentle rewarming up to 20°C (COR20) or 35°C (COR35) was studied in rat livers and compared with cold storage alone (CS, n = 6, resp). Postpreservation recovery was evaluated upon warm reperfusion using an established in vitro system. COR generally resulted in significantly improved energetic recovery, increased bile flow, less activities alanine aminotransferase (ALT) release, and improved histopathology upon reperfusion as compared to only cold-stored livers, without significant differences between COR20 and COR35.Parameters obtained during COR, especially during COR35, also allowed for prediction of hepatic recovery upon reperfusion. For instance, ulterior bile production upon reperfusion was found closely correlated to bile flow observed already during COR35 (R 2 = 0.91). COR significantly improved liver quality after static cold storage. Elevation of machine perfusion temperature up to 35°C may prove promising to refine ex vivo evaluation of the graft prior to transplantation. K E Y W O R D Scontrolled oxygenated rewarming, liver preservation, machine perfusion, organ reconditioning | INTRODUCTIONOne of the major restrictions in transplantation medicine is the limited number of available donor organs. Due to this imbalance between donor organs and waiting recipients, the criteria of organ selection were extended and grafts of lesser quality became increasingly accepted to be transplanted. 1 The use of these "less-than-optimal" grafts provides new challenges in transplantation research with regard to organ preservation and conditioning. 2 New ex vivo strategies for maintenance and improvement of organ function could prevent storage and reperfusion-induced tissue injury and could therefore result in decreased post-transplantation graft dys-or nonfunction. 3Organ preservation traditionally includes flush-out with appropriate preservation solutions followed by cold storage under hypoxic conditions. 4 Problems associated with this technique are hypoxiainduced apoptotic events as well as activation of pro-inflammatory mediators, which influence post-transplantation organ function and integrity. 5 Previous research evidenced that main destructive effects rather establish during exposure of organs to blood circulation after implantation than during the ischemic cold storage period itself. 6This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Role of erythrocytes in short‐term rewarming kidney perfusion after cold storage

“…For this purpose we used AQIX RS-I, a novel preservation solution with a physiological extracellular composition pattern, comprising a combination of amino acids, metabolic substrates, vitamins and organic buffers. Its specific buffer system allows for a constant pH over a broad range of temperatures from cold to warm and its normal ion milieu could favor cellular re-equilibration by aerobic supplementation (26). In terms of a suitable solution for the reconditioning perfusion, data of this study are in line with a previous report using diluted Steen solution as a perfusate for controlled rewarming of kidney grafts.…”

Cold flush after dynamic liver preservation protects against ischemic changes upon reperfusion - an experimental study

“…In the case of subnormothermic machine perfusion, which has proven comparably effective by several groups [23][24][25], the need for secondary cooling of the previously rewarmed graft becomes even more controversial.…”

First-in-man controlled rewarming and normothermic perfusion with cell-free solution of a kidney prior to transplantation

“…Further slowing down of the rewarming process did not produce superior results in preclinical experiments. 19 However, an extension of the normothermic perfusion period beyond the intended 2 hours might be indicated, in case of irregularities with the patient preparation. The use of a cell-free perfusate facilitates the procedure and furthermore precludes the risk of residual cell material in red blood cell preparation or hemolysis during machine perfusion that could entail adverse effects to the graft.…”