Use of modified Custodiol-N as perfusion solution in ex vivo lung perfusion.

Ex vivo Lung Perfusion (EVLP) is a promising tool to increase the donor pool for lung transplantation. Custodiol-N solution was originally designed for organ preservation during cold static preservation (CSP) and was successfully used for machine perfusion in kidneys. It was the aim of this study to compare the lung functional outcomes after 4 hours of EVLP using modified Custodiol-N or STEEN SolutionTM as perfusion solution. In a porcine DCD model, lungs were perfused either with STEEN SolutionTM (Standard SS, n=8) or modified Custodiol-N with added 1.1 g/l glucose monohydrate and 50 g/l dextran 40 (CD, n=8). For a third group 7 g/l albumin was supplemented to modified Custodiol-N (CDA, n=8). During four hours of EVLP pulmonary gas exchange and activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) in perfusate were recorded. Lungs that underwent EVLP with modified Custodiol-N showed significantly higher oxygen capacity (ΔpO2 averaged over four hours of EVLP: SS: 236.28 ± 47.26 mmHg, CD: 402.79 ± 30.33 mmHg, CDA: 414.86 ± 9.77 mmHg) than lungs perfused with STEEN SolutionTM. The addition of albumin did not have a significant effect on lung function but these lungs showed lower wet/dry ratio. In a porcine DCD model of 9 hours CSP followed by four hours of EVLP the use of modified Custodiol-N as perfusion solution was feasible and associated with higher oxygen capacity than STEEN SolutionTM. The addition of albumin seems to further stabilize lung function.

Olbertz C ，Pizanis N ，Bäumker H ，Kalka K ，Aigner C ，Rauen U ，Nolte I ，Kamler M ，Koch A ... -  《American Journal of Translational Research》

Custodiol-MP for ex vivo lung perfusion - A comparison in a porcine model of donation after circulatory determination of death.

Kalka K ，Keldenich Z ，Carstens H ，Walter B ，Rauen U ，Ruhparwar A ，Weymann A ，Kamler M ，Reiner G ，Koch A ... -  《-》

Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities. Following cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays. Within 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1β increased significantly (P < 0.05) in all experimental groups. The CD solution contained lower concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, and IL-18 (P < 0.05) compared with those of the Steen solution. The concentration levels of all experimental groups have correlated negatively with the oxygenation capacity values (P < 0.05). Protein concentration levels did not reach statistical significance for I-EVLP vs. D-EVLP and CD vs. CDA solutions. In a porcine cardiac arrest model, a longer period of CSP prior to EVLP did not result in an enhanced protein secretion into perfusates. The CD solution reduced the cytokine/chemokine secretion most probably by iron chelators and/or by the protecting effects of dextran. Supplementing with albumin did not further reduce the cytokine/chemokine secretion into perfusates. These findings may help in optimizing the preservation procedure of the lungs, thereby increasing the donor pool of organs.

Radomsky L ，Koch A ，Olbertz C ，Liu Y ，Beushausen K ，Keil J ，Rauen U ，Falk CS ，Kühne JF ，Kamler M ... -  《Frontiers in Cardiovascular Medicine》

Effects of immediate versus delayed ex-vivo lung perfusion in a porcine cardiac arrest donation model.

Olbertz C ，Pizanis N ，Bäumker H ，Becker S ，Aigner C ，Rauen U ，Nolte I ，Kamler M ，Koch A ... -  《-》

Porcine slaughterhouse lungs for ex vivo lung perfusion - a pilot project.

Ex vivo lung perfusion (EVLP) is an emerging technique for evaluation and eventual reconditioning of donor lungs. Before clinical use experiments with laboratory animals are standard. It was the aim of this study to compare lungs evaluated with EVLP from laboratory animals with slaughterhouse lungs and to investigate the potential use of a slaughterhouse lung model for ex vivo lung perfusion as an alternative for the use of laboratory animals. In a porcine model of Donation after Circulatory Determination of Death (DCDD) 16 lungs were obtained either from regular slaughterhouse animals (SL n = 8) or from laboratory animals in organ procurements (SS n = 8). Lungs were flushed and stored cold for four hours in Perfadex Plus™ and subsequently perfused ex vivo with Steen Solution™ for up to four hours. During 4 hours of EVLP lung functional parameters and activities of lactate, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) in the perfusate were recorded hourly. Histological samples were taken and evaluated fur Lung Injury. Lungs showed no significant difference in oxygen capacity in between groups (∆ PO2 averaged over 4 hours: SL 293 ± 187 mmHg SS 247 ± 199 mmHg). LDH concentration was significantly higher in slaughterhouse lungs (SL 438,5 ± 139,8 U/l, SS 258,42 ± 108,4 U/l P ≤ 0,01). We conclude that the use of slaughterhouse lungs for EVLP was feasible with no significant disadvantages compared to standard organ procurement lungs regarding lung functional outcomes. With the use of slaughterhouse lungs animal experiments in EVLP research could be successfully reduced.

Kalka K ，Keldenich Z ，Carstens H ，Hilken G ，Olbertz C ，Pizanis N ，Kamler M ，Reiner G ，Koch A ... -  《American Journal of Translational Research》