Oakley, RB and Tingay, DG and McCall, KE and Perkins, EJ and Saurial, M and Dargaville, PA and Pereira-Fantini, PM, Gestational age influences the early microarchitectural changes in response to mechanical ventilation in the preterm lamb lung, Frontiers in Pediatrics, 7 Article 325. ISSN 2296-2360 (2019) [Refereed Article]
Copyright 2019 Oakley, Tingay, McCall, Perkins, Sourial, Dargaville and Pereira-Fantini. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Method: Lung morphology was compared after 60 min of a standardized ventilation protocol (40 cm H2O sustained inflation and then volume-targeted positive pressure ventilation with positive end-expiratory pressure 8 cm H2O) in lambs at different gestations (119, 124, 128, 133, 140d) representing the spectrum of premature developmental lung states and the term lung. Age-matched controls were compared at 124 and 128d gestation. Automated and manual functions of Image J were used to measure key histological features. Correlation analysis compared morphological and functional outcomes in lambs aged ≤128 and >128d.
Results: In initial studies, unventilated lung was indistinguishable at 124 and 128d. Ventilated lung from lambs aged 124d gestation exhibited increased numbers of detached epithelial cells and lung tissue compared with 128d lambs. Comparing results from saccular to alveolar development (120-140d), lambs aged ≤124d exhibited increased lung tissue, average alveolar area, and increased numbers of detached epithelial cells. Alveolar septal width was increased in lambs aged ≤128d. These findings were mirrored in the measures of gas exchange, lung mechanics, and molecular markers of lung injury. Correlation analysis confirmed the gestation-specific relationships between the histological assessments and functional measures in ventilated lambs at gestation ≤128 vs. >128d.
Conclusion: Image J allowed rapid, quantitative assessment of alveolar morphology, and lung injury in the preterm lamb model. Gestational age-specific patterns of injury in response to delivery of an identical ventilation strategy were identified, with 128d being a transition point for associations between morphological alterations and functional outcomes. These results further support the need to develop individualized respiratory support approaches tailored to both the gestational age of the infant and their underlying injury response.
|Item Type:||Refereed Article|
|Keywords:||preterm, lamb model, mechanical ventilation, lung injury, alveolarization, lung morphology|
|Research Division:||Medical and Health Sciences|
|Research Group:||Paediatrics and Reproductive Medicine|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Respiratory System and Diseases (incl. Asthma)|
|UTAS Author:||Dargaville, PA (Professor Peter Dargaville)|
|Deposited By:||Menzies Institute for Medical Research|
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