Abstract
BACKGROUND: Current clinical ex vivo lung perfusion (EVLP) perfuses the pulmonary arteries (PA) but not the bronchial arteries (BA) that normally supply the upper airway. We hypothesized that the PA alone do not fully perfuse this region during EVLP, which could lead to hypoxic injury in the central airways, especially with extended preservation. In this study, we demonstrate a method for dual-route EVLP (D-EVLP) that perfuses both the PA and BA to improve lung preservation. METHODS: Lungs were procured from 30- to 40-kg female pigs and perfused for up to 3 hours. Standard single-route control EVLP (C-EVLP) was compared to a D-EVLP approach consisting of PA inflow along with oxygenated BA inflow via cannulation through a segment of the thoracic aorta to achieve bronchoesophageal artery circulation. RESULTS: Airway perfusion by BA flow was confirmed by injecting methylene blue. The mean total perfusion flows of D-EVLP and C-EVLP were 915 ± 60.2 mL/minute and 645 ± 46.5 mL/minute at 3 hours, respectively. Lower vascular resistance also was observed with D-EVLP (mean, 878 ± 109 dynes∗second/cm(5) vs 1689 ± 194 dynes∗second/cm(5)). The PaO(2)/fraction of inspired oxygen ratio (mean, 589 ± 28 for D-EVLP, 587 ± 20 for C-EVLP) and dynamic compliance (30.8 ± 3.0 mL/cmH(2)O for D-EVLP, 30.3 ± 6.3 mL/cmH(2)O for C-EVLP) were comparable after 3 hours of preservation. In central and distal airways, hypoxia-inducible factor 1α, a marker of hypoxia measured by immunohistochemistry, was lower in D-EVLP compared to C-EVLP. CONCLUSIONS: The present study demonstrates the D-EVLP is feasible in a large-animal model and provides evidence that it may reduce airway ischemia compared to standard EVLP. Further investigation is warranted to determine the extent to which D-EVLP elicits superior graft preservation during extended perfusion and, ultimately, post-transplantation outcomes.