Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Autor:	Hermans BP; Department of Cardio-Thoracic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Li WWL; Department of Cardio-Thoracic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Roozen EA; Department of General Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van Dort DIM; Department of Cardio-Thoracic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Vos S; Department of Pathology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van der Heide SM; Department of Cardio-Thoracic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van der Heijden EHFM; Department of Pulmonology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Ten Broek RPG; Department of General Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., van Goor H; Department of General Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Verhagen AFTM; Department of Cardio-Thoracic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of thoracic disease [J Thorac Dis] 2023 Sep 28; Vol. 15 (9), pp. 4703-4716. Date of Electronic Publication: 2023 Aug 30.
DOI:	10.21037/jtd-23-180
Abstrakt:	Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo , extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo . Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo , lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-180/coif). EAR is an employee of GATT Technologies B.V. and HvG was a scientific advisor for GATT Technologies B.V. until 31 December 2021, but not in relation to lung sealing technology. BPH received funding and study materials through the institution for conduction of the study from GATT Technologies B.V. The other authors have no conflicts of interest to declare. (2023 Journal of Thoracic Disease. All rights reserved.)
Databáze:	MEDLINE
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