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

Abstract

Objective: Ex-vivo lung perfusion is a promising tool to evaluate and recondition marginal donor lungs usually after a cold static preservation. The concept of continuous organ perfusion is supposed to reduce ischemic damage; however, the optimal perfusion protocol has not been established yet. The aim of this study was to compare immediate ex-vivo lung perfusion (I-EVLP) to delayed ex-vivo lung perfusion (D-EVLP) after a certain cold static preservation period on lung function in a large animal model. Methods: In a porcine model, lungs were procured after circulatory death and 60 min of no-touch warm ischemia. Lungs were preserved with single-flush cold low potassium dextran solution and prepared either for I-EVLP (n = 8) or stored cold for 9 h with subsequent D-EVLP (n = 8). Functional outcomes and morphology were compared during 4 h of ex-vivo lung perfusion, using STEEN SolutionTM as perfusion solution. Results: Pulmonary functional data, perfusate activities of lactate dehydrogenase, alkaline phosphatase, and products of lipid peroxidation did not differ significantly. There was a trend toward lower wet–dry ratio (I-EVLP: 13.4 ± 2.9; D-EVLP: 9.1 ± 2.5) and higher ΔpO2 in D-EVLP group (I-EVLP: 209 ± 51.6 mmHg; D-EVLP: 236.3 ± 47.3 mmHg). Conclusion: In this donation-after-circulatory-death model, 9 h of cold static preservation followed by ex-vivo lung perfusion results in comparable pulmonary function to I-EVLP as indicated by oxygenation capacities and wet–dry ratio. Our findings indicate that prolonged cold static preservation prior to ex-vivo lung perfusion is as safe and effective as I-EVLP in the procurement of donor lungs.

Endothelin-Converting Enzyme 1 and Vascular Endothelial Growth Factor as Potential Biomarkers during Ex Vivo Lung Perfusion with Prolonged Hypothermic Lung-Sparing

“…The evaluation of I-EVLP and D-EVLP groups was similar; even though I-EVLP presented a rise in the wet-dry weight ratio and lightly augmented histological findings, and oxygenation capacity (partial oxygen pressure at FiO 2 of 100%) in both groups was maintained at above-expected values for EVLP lungs [22,23]. Our data matched other studies that found that lungs with D-EVLP maintain pulmonary function in a significant way [12] and showed in a porcine model that EVLP with prior cold static preservation for nine hours is as safe and effective as I-EVLP of donor's lungs procurement [13].…”

“…Compliance of lung tissue was comparable in both groups, but a trend to higher Cstat and Cdyn in the I-EVLP group was observed. The slight compliance decrease in D-EVLP may be due to longer hypothermia, which would slow the process of reaching the same lung elasticity as in the I-EVLP group [13]. The PIP remained at the same level in both groups during EVLP, with higher values in D-EVLP; however, in porcine models, PIP is higher compared to human lungs [13], and although there was a significant difference between groups, the Δ peak-plateau was not greater than 5 cm H 2 O. Airway and vascular pressures remained stable for 4 h. All other measured lung functional parameters, in both groups, did not differ.…”

“…Currently, applying the EVLP platform, it has been demonstrated that lung viability can be successfully maintained despite a prolonged period of cold preservation [11][12][13]. This may be especially relevant in situations or places where lung procurement is difficult or far from the transplantation site (a frequent problem in developing countries) so that the graft has to be maintained at hypothermic conditions for prolonged periods.…”

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

“…3 Steen Solution™ is designed as a modified low potassium dextran solution with 70 g/l human serum albumin as major adjuvant. 5,6 Lungs undergoing ischemia present a typical postischemic reperfusion injury (LIRI). 7 Since primary graft dysfunction (PGD) due to LIRI is common in lung transplantations, the development of a safe and reliable technique preventing LIRI would contribute to the improvement of transplanted lungs.…”

“…Hence, the composition of the perfusion solution used for EVLP seems to be crucial for EVLP's success. 2,6,7,10,11 The composition of the perfusion solution directly influences colloid osmotic pressure and antioxidative properties to reduce ROS (reactive oxygen species) formation and prevent the organ from excessive reperfusion injury. 2,11 Recent studies have investigated antioxidative properties of Steen Solution TM and discovered a specific downregulation of NOX 2 activity.…”