Background
Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support
and recovery that could expand the pool of donor lungs suitable for transplantation.
The objective of this study was to establish and validate a standardized, reproducible,
and broadly applicable technique for performing xenogeneic XC to support and recover
injured human donor lungs ex vivo.
Methods
Human donor lungs (n = 9) declined for transplantation were procured, cannulated, and subjected to 24
hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated
with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus)
and complement-depleting cobra venom factor. Standard lung-protective perfusion and
ventilation strategies, including periodic lung recruitment maneuvers, were used throughout
xenogeneic XC. Every 6 hours, ex vivo donor lung function (gas exchange, compliance,
airway pressures, pulmonary vascular dynamics, lung weight) was evaluated. At the
experimental endpoint, comprehensive assessments of the lungs were performed by bronchoscopy,
histology, and electron microscopy. Student's t-test and 1-way analysis of variance with Dunnett's post-hoc test was performed, and
p < 0.05 was considered significant.
Results
After 24 hours of xenogeneic XC, gas exchange (PaO2/FiO2) increased by 158% (endpoint:
364 ± 142 mm Hg; p = 0.06), and dynamic compliance increased by 127% (endpoint: 46 ± 20 ml/cmH2O; p = 0.04). Airway pressures, pulmonary vascular pressures, and lung weight remained
stable (p > 0.05) and within normal ranges. Over 24 hours of xenogeneic XC, gross and microscopic
lung architecture were preserved: airway bronchoscopy and parenchymal histomorphology
appeared normal, with intact blood–gas barrier.
Conclusions
Xenogeneic cross-circulation is a robust method for ex vivo support, evaluation, and
improvement of injured human donor lungs declined for transplantation.
Keywords
Abbreviations:
CVF (cobra venom factor), EVLP (ex vivo lung perfusion), IJV (internal jugular vein), PA (pulmonary artery), PV (pulmonary vein), TPG (transpulmonary pressure gradient), XC (cross-circulation)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 14, 2022
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© 2022 International Society for Heart and Lung Transplantation. All rights reserved.
