Novel Therapy: Extra Corporal Hemoperfusion Regenerated Pulmonary Function and Reduce Primary Graft Dysfunction in an ARDS Pig EVLP and Lung Transplantation Model

Abstract

<h3>Purpose</h3> Despite improvements in lung transplantation (LTx), severe primary graft dysfunction (PGD) remains the leading cause of early mortality. In addition, a major challenge to LTx as a therapy, is the scarcity of donor organ. One major reason for rejecting a lung donor offer is acute lung injury in fear for severe PGD. To increase the number of donor organs, the possibilities of repairing damaged lungs is appealing. Cytokine filtration has shown to have an immunomodulation capacity and might therefore increase the tolerability towards the donor organ. <h3>Methods</h3> In the present study we induce acute respiratory distress syndrome (ARDS) using lipopolysaccharide (LPS) in donor pigs. Lungs where then treated with or without a cytokine filtration system in two steps. The first treatment step occurs during the use of ex vivo lung perfusion (EVLP). The left lung was subsequently transplanted, and treatment step two was initiated using ex vivo hemoperfusion in the recipient. The transplanted lung was thereafter evaluated after a right pneumonectomy to evaluate the impact on PGD at 48 hours. Figure 1) Overview. Figure 2a) Filtration EVLP 2b) Hemoperfusion recipient <h3>Results</h3> All pulmonary grafts had moderate to severe ARDS at the initiation of EVLP. Over the course of EVLP, the treated lungs increased their gas exchange capacity.The treated group required significantly less inotropic support post-transplantation and showed improved hemodynamic stability compared to the control group. During the first day post-transplantation no significant difference could be seen in the gas exchange between the groups. During the second day, however, and especially after the right pneumonectomy, a significant increase in gas exchange could be seen in the treated group compared to the controls. <h3>Conclusion</h3> Hemoperfusion post transplantation using cytokine filtration did regenerate lung function in ARDS injured donor lungs and did significantly reduced PGD.