The role of leukocyte depletion in ex vivo evaluation of pulmonary grafts from (non-)heart-beating donors

Abstract

If lungs could be retrieved for transplantation after circulatory arrest, the shortage of donors might be significantly alleviated. An important issue in using lungs from these so-called non-heart-beating donors is the development of a technique to assess their quality prior to transplantation without jeopardizing the life of the recipient. In our laboratory we tested the reliability of an ex vivo model for such an evaluation. We used pig lungs from optimal control animals, in casu heart-beating donors. This model enabled us to preserve and evaluate lungs with perfect function up to 24 hours after death. The intermediate assessment is performed in an isolated circuit where the lungs are being ventilated and reperfused via the pulmonary artery (PA) with autologous and haemodiluted blood. Haemodynamic, aerodynamic and oxygenation parameters are measured at 37.5 degrees C and a maximum PA pressure of 20 mmHg. These data were correlated with premortem values. During this ex vivo evaluation, leukocyte depletion plays an important role since neutrophils have been recognized as critical components in the inflammatory cascade, which is responsible for graft dysfunction soon and long after transplantation.

Results of Clinical Lung Transplant From Uncontrolled Non-Heart-Beating Donors

“…We are monitoring with great interest the experiences from Steen et al 22 and Rega et al [23][24][25] with the ex-vivo reperfusion model, which may be useful not only to assess in a standard reproducible way the functional viability of these grafts but also to improve Figure 1. Duration of primary graft dysfunction, where P25 is the 25th percentile, P50 is the 50th percentile, P75 is the 75th percentile, and P/F is the partial pressure of arterial oxygen (PAO 2 )/fraction of inspired oxygen (FIO 2 ) ratio.…”

IL-1β in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor

“…In our laboratory we also have extensive experience with such an ex vivo reperfusion model in over 200 pig lung experiments. [22][23][24][25] In our opinion, ex vivo assessment is a safe and accurate method to test the quality of the pulmonary graft from the NHBD but it remains a cumbersome, time consuming, and invasive procedure. mAwP, and W/D.…”

“…This does not implicate that our isolated reperfusion model was free of leukocytes and thereby free of a leukocyte-mediated response. 24 To prepare a leukocyte-free reperfusion solution, the whole blood needs to be centrifuged with sufficient gravitational force. The remaining packed cells should be filtered using a leukocyte filter.…”

Do we need to cool the lung graft after ex vivo lung perfusion? A preliminary study

“…EVLP of the double lung block was performed with 1.7 L of a home-made acellular solution as in previous studies [9]. The perfusate was based on Perfadex with 60 g/L albumin added and finalized with heparin 10,000 IU, methylprednisolone 500 mg, and cefazolin 1 g.…”