Retrograde oxygen persufflation preservation of human livers: A pilot study

Abstract

Retrograde oxygen persufflation as a supplement of cold storage during the preservation period has the potential to better utilize ischemically damaged marginal livers in the experimental setting. Retrograde oxygen persufflation was applied in selected livers to demonstrate feasibility in the clinical setting and to investigate potential beneficial effects. Between 4/04 and 3/05 5 marginal otherwise discarded livers with warm ischemic damages from deceased donors (age 52 ) were accepted for transplantation. All organs were distantly procured and shipped to our center. Immediately after arrival, filtered humidified gaseous oxygen was given via the hepatic veins for at least 60 minutes with a pressure up to 18 mm mercury. Liver biopsies were analyzed for ATP content before and after persufflation. All patients (age 55 [46 -66]) survived without retransplantation, had good initial function and are alive and well after minimum follow-up of two years. Bleeding from pinpricks stopped spontaneously after 5-10 minutes after reperfusion but was prolonged in one patient with severe coagulopathy until correction. One patient developed arterial thrombosis at postop day 0. He fully recovered after thrombectomy. Another patient developed subcapsular hematoma, which was removed at postop day 10. On routine postoperative biopsies vascular structures appeared undamaged. ATP levels in pre-reperfusion biopsies revealed a more than twofold increase of ATP content compared to biopsies before persufflation. Retrograde oxygen persufflation preservation is feasible and save in the clinical setting, improves early aerobic metabolism and therefore potentially improves primary organ function after liver transplantation. Organ shortage is the main problem in liver transplantation leading to a high mortality rate on the waiting list. Possible mechanisms to alleviate this difficulty include extension of living donations, split liver transplantation, and, increasingly, the use of marginal organs. 1 The outcome of the use of potentially critical marginal organs could be enhanced by the improvement of preservation and revitalization techniques applied during the cold ischemia time period.Experimental studies investigating the effect of hypothermic liver perfusion pump systems with oxygenation reveal promising results. 2,3 However, these perfusion system machines are expensive, technically complex, and not yet fully developed for clinical application. 4 Machine perfusion, although analyzed in experimental studies up to now, does not have a clinical impact on the preservation of livers.In several ex vivo studies and recently in an in vivo study, we demonstrated successful extension of ischemic tolerance of porcine livers by cold preservation including postconditioning with gaseous oxygen [retrograde oxygen persufflation (ROP)]. 5,6 Also, the detrimental effects of 60 minutes of warm ischemia for kidneys were completely reversible with ROP. 7 On the basis of our experimental results, we applied ROP in Abbreviations: ALAT, alanine aminotransferase;...

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

“…For kidney preservation, VSOP was first described by Talbert et al [15] in 1961, and has since then demonstrated the capability of extending the allowable warm and cold ischemia times as well as better maintenance of organ viability when compared to CS and MP [8,11,16]. In the past decades, the feasibility of the clinical application of VSOP was demonstrated in a kidney and a liver preservation feasibility study [17,18]. …”

A Novel Organ Preservation for Small Partial Liver Transplantations in Rats: Venous Systemic Oxygen Persufflation With Nitric Oxide Gas

“…In experimental studies (2,3); VSOP reduced apoptosis; and improved graft viability by increasing tissue adenosine triphosphate (ATP) concentration, vascular endothelial function and ultrastructure in several models. In a clinical pilot study for deceased-DLT, Treckmann et al (14) reported that the VSOP during cold storage increased ATP more than twofold and, thus, improved early aerobic metabolism; therefore, the VSOP could potentially improve primary organ function after liver transplantation.…”

Potential approaches to improve the outcomes of donation after cardiac death liver grafts

“…Liver grafts underwent R-PSF at 18 mmHg at least one hour before transplantation. Evaluation of the histological biopsies taken before and after R-PSF showed that ATP level was enhanced by 2-5 times after R-PSF treatment, and all the patients survived during the two years of observation period with good graft function panel [16] .…”

“…They first established the model on rodent liver and continued with large animals (pig) and were able to demonstrate the benefits of PSF by improving the quality of liver grafts [15] . They also showed the feasibility of this method by publishing the outcome of five patients transplanted with persufflated livers [16] . The livers underwent WIT between 20-60 min and they were rejected by all the other transplant centers for transplant.…”