TY - JOUR

T1 - Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique

AU - Buttar, Sana N.

AU - Møller-Sørensen, Hasse

AU - Perch, Michael

AU - Kissow, Hannelouise

AU - Lilleør, Thomas N.B.

AU - Petersen, Rene H.

AU - Møller, Christian H.

N1 - Publisher Copyright: Copyright © 2024 Buttar, Møller-Sørensen, Perch, Kissow, Lilleør, Petersen and Møller.

PY - 2024

Y1 - 2024

N2 - The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p <.05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

AB - The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p <.05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

KW - cellular/acellular perfusate

KW - ex vivo lung perfusion

KW - ex vivo lung perfusion duration

KW - ex vivo lung perfusion strategies

KW - open/closed atrium

KW - prolonged ex vivo lung perfusion

U2 - 10.3389/fbioe.2024.1357182

DO - 10.3389/fbioe.2024.1357182

M3 - Journal article

C2 - 38983601

AN - SCOPUS:85197683479

VL - 12

JO - Frontiers in Bioengineering and Biotechnology

JF - Frontiers in Bioengineering and Biotechnology

SN - 2296-4185

M1 - 1357182

ER -