Effects of exogenous surfactant on the non‐heart‐beating donor lung graft in experimental lung transplantation – a stereological study |
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Authors: | Navid Madershahian Christian Mühlfeld Konrad Frank Parwis Rahmanian Thorsten Wahlers Thorsten Wittwer Matthias Ochs |
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Affiliation: | 1. Department of Cardiothoracic Surgery, University Hospital Cologne, , Cologne, Germany;2. Institute of Functional and Applied Anatomy, Hannover Medical School, , Hannover, Germany;3. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, , Germany;4. REBIRTH Center of Excellence, , Hannover, Germany;5. Department of Cardiology, Pneumology, Angiology and Intensive Care Medicine, Heart Center, University Hospital of Cologne, , Germany;6. Center of Molecular Medicine, University of Cologne, , Cologne, Germany |
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Abstract: | The use of non‐heart‐beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non‐SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design‐based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham‐operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non‐SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron‐chovascular connective tissue. Regarding intra‐alveolar oedema, no statistically significant difference could be found between SF and non‐SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart‐beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are limiting factors that need to be addressed in NHBD. |
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Keywords: | I/R injury non‐heart‐beating donor lung graft pig model stereology surfactant |
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