Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys

Abstract

Background/Aim: The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. Results: During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. Conclusion: VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia-damaged porcine kidneys by VSOP was improved compared to OMP and CS, and was comparable to preservation of non-warm-ischemia-damaged cold-stored kidneys.

Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications

“…Due to the fact that most of the therapeutic interventions were tested during NMP, only limited data are available with in vivo therapeutics in HMP/HOPE [82,85,86]. Optimized perfusion solutions for HMP/HOPE containing amino acids, metabolic substrates, vitamins, and organic buffers have been investigated in kidneys and other organs showing the potential benefits in terms of post-transplant graft function [82,88,89].…”

Machine perfusion for liver transplantation in the era of marginal organs—New kids on the block

“…Current clinical strategies are unable to fulfil the demands presented by the transplantation of so‐called marginal grafts, and the need for optimized preservation techniques that address the underlying impairment of ECD allografts is paramount. In recent years, the main research focus of several groups, including ours, has therefore been the development of improved organ preservation and organ conditioning approaches . Machine perfusion (MP) has been recognized as a promising preservation strategy in the context of OLT using ECD allografts.…”

“…In recent years, the main research focus of several groups, including ours, has therefore been the development of improved organ preservation and organ conditioning approaches. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Machine perfusion (MP) has been recognized as a promising preservation strategy in the context of OLT using ECD allografts. While SCS only prolongs storage time and limits the damage sustained during the period of cold ischaemia, MP even appears to be capable of reversing some of these effects.…”

Hypothermic Oxygenated Machine Perfusion of Extended Criteria Kidney Allografts from Brain Dead Donors: Protocol for a Prospective Pilot Study

“…Dynamic organ preservation approaches, such as machine perfusion, hold promise for improving organ preservation and resuscitation of marginal donor allografts [6-9]. Although tissue oxygen consumption is markedly decreased at 4-10°C, there is still relevant metabolism at this temperature.…”

“…In the preclinical setting, the positive effects of HOPE have recently been demonstrated through a reduction in the incidence of tubular damage, macrophage activation, and functional optimization of cellular energy-status in vitro and in vivo [8,9,11]. There are several hypotheses regarding the underlying mechanisms of HOPE-induced organ protection.…”