Background : The widespread application of lung transplantation (LTx) is still limited by a critical organ shortage. According to current donor criteria, about 70-80% of donor lungs are declined for transplantation, the majority because of edema, contusion, aspiration, or pneumonia. If the quality of these organs could be adequately improved outside the donor, some of these lungs might still become suitable for LTx.
Objective : The purpose of this study was to assess feasibility of isolated reperfusion of human lungs as a first step in the search to condition lungs of inferior quality outside the donor.
Methods : Permission was obtained from our local ethical committee (19-02-2002). All lungs from locoregional donors that had been declined by our as well as other Eurotransplant LTx teams were considered for ex vivo reperfusion. Lungs were harvested in the standard way using an anterograde flush (60 mL/kg) of cold (4°C) Perfadex®, then explanted and further stored in an icebox. After cannulation, lungs were placed in isolated model and gradually ventilated (FiO2=1.0, PEEP=5 cm H20, MV=100 mL/kg) and reperfused up to 2 hours in a closed, pressure-controlled (15 mm Hg) circuit with a mixture (3L) of deoxygenated (PO2=60 mm Hg) ABO-compatible human red blood cells and Steen Solution®. Graft function was assessed by measuring hemodynamic (mPAP, Flow, PVR) as well as aerodynamic parameters (peak and mean AwP) and outflowing PO2.
Results : Over a period of 17 months, 20 paired human lungs have been evaluated in our ex vivo system. Donor characteristics were as follows: mean ± SEM age: 46 ± 4 years; M/F: 14/6; blood group O/A/B/AB: 12/8/0/0; cause of brain death : CVA (n=13), CCT (n=6), tumor (n=1). The organs had been declined for LTx for the following reasons: contusion (n=3), poor gas exchange (n=3) , pneumonia (n=4), donor high age (n=4), emphysema (n=2), edema (n=1), donor malignancy (n=1), and not allocated (n=2). Oxygenation Index (PO2/FiO2) (FiO2=1.0, PEEP=5 cm H2O) measured prior to organ extraction was 311 ± 47 mm Hg. Lungs were reperfused after a cold ischemic interval of 848 ± 58 min. Pulmonary graft parameters during the 2-hour reperfusion period remained stable in all experiments and are presented in Table.
| Reperfusion Time |
30' |
60' |
90' |
120' |
| Flow (L/min) |
1.6 + 0.1 |
1.9 + 1.1 |
2.0 + 0.1 |
1.9 + 0.1 |
| PVR (dynes.sec.cm-5) |
745 + 83 |
686 + 66 |
680 + 79 |
572 + 174 |
| Peak AwP (mm Hg) |
18.9 + 1.4 |
17.8 + 1.1 |
17.5 + 1.0 |
16.2 + 2.0 |
| Mean AwP (mm Hg) |
6.8 + 0.4 |
7.4 + 0.4 |
7.4 + 0.3 |
6.7 + 0.7 |
| PO2/FiO2 (mm Hg) |
428 + 30 |
434 + 31 |
458 + 33 |
413 + 41 |
Conclusions : Ex vivo reperfusion of human lungs is technically feasible and can be performed in a stable manner for at least 2 hours without (further) graft deterioration. This model offers a unique opportunity to study ex vivo conditioning of lungs with inferior quality. It can also be used to assess the function of lungs retrieved from donors after circulatory arrest prior to implantation.
(supported by grants from FWO-Vlaanderen G.3C04.99, G.0093.02 and KUL-Onderzoeksfonds OT/TBA/41, OT/03/55)
(the Steen Solution® was kindly provided by Vitrolife, Gothenburg, Sweden)