Endothelial integrity as a major factor in cold preservation of lung for transplantation

• Main Author: Hidalgo-Simon, Maria Ana
• Format: Dissertation
• Language: English
• Published: University of London 1996
• Subjects: Donor lungs; Pulmonary physiology

The current shortage of donor lungs for transplantation could be partially solved by increasing the safe cold preservation time for pulmonary tissue. This study was undertaken to investigate the hypothesis that cold preservation leads to damage to the pulmonary endothelium, resulting in loss of the normal permeability barrier and consequent overwhelming oedema. Improvements in lung preservation would follow if normal endothelial cell functions could be maintained. The studies were based on (a) a single lung transplantation model in rats; and (b) w vitro cultures of human endothelial cells (EC). a. Whole lung transplantation was studied using light and electron microscopy, radiology and long-term survival with blood gas analysis of pulmonary physiology. b. In vitro studies were based on morphology and viability measured in cultures of confluent EC exposed to cold ischaemia and warm re-oxygenation. Permeability studies to measure leakage of Evan's blue-conjugated albumin across the monolayer were performed on transwell membranes. The data obtained suggested that fluid extravasation from blood vessels to alveoli due to poorly preserved endothelium is the main cause of organ failure after lung transplantation. The results from EC suggested that morphological changes and monolayer continuity were closely related and could have a determinant role in maintaining vascular permeability. The long term survival studies showed the great capacity of lung tissue to recover from oedema and haemorrhage with little histological damage but some electron microscopic changes 4 weeks after transplantation. When different preservation solutions were tested, these differed in grades of effectiveness in vivo and in vitro. Permeability studies suggested that drugs modulating cAMP levels could be used to prevent permeability rise due to cold ischaemic storage. Preservation of EC morphology and monolayer continuity should be studied in greater depth to improve pulmonary preservation in future.