1. Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs
- Author
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Jorge Juan Olsina-Kissler, Susana Gómez-Ollés, Cristina Esquinas, Meritxell Boada-Pérez, Amaia Ojanguren, Maite Santamaría, Alba Boldó, Sonia Gatius-Calderó, Carlos Fraile, Berta Sáez-Giménez, Iñigo Ojanguren, Miriam Barrecheguren, Lucia Milla-Collado, and Sara Puy
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Swine ,medicine.medical_treatment ,Ischemia ,Pilot Projects ,Lung injury ,Gastroenterology ,Proinflammatory cytokine ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Apoptosis Marker ,Lung transplantation ,Lung ,Caspase 3 ,business.industry ,Lung Injury ,Organ Preservation ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,030228 respiratory system ,Apoptosis ,Reperfusion Injury ,Cytokines ,business ,Reperfusion injury ,Lung Transplantation - Abstract
Background In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. Methods Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n = 8) were submitted to organ procurement. Lungs were subjected to 6 h (n = 4) or 12 h (n = 4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4 h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30 min after reperfusion, and (iv) 4 h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. Results We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6 h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30 min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30 min after reperfusion. Conclusions We observed that 6 and 12 h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.
- Published
- 2021
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