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. 2023 Oct 18;7(1):e1295.
doi: 10.1002/jsp2.1295. eCollection 2024 Mar.

Ovine model of congenital chest wall and spine deformity: From birth to 3 months follow-up

Affiliations

Ovine model of congenital chest wall and spine deformity: From birth to 3 months follow-up

Jesse Shen et al. JOR Spine. .

Abstract

Background: The evolution and treatment of lung alterations related to congenital spine and chest wall deformities (CWD) are poorly understood. Most animal models of CWD created postnatally were not evaluated for respiratory function. The goal of our study was to evaluate the effects of a CWD induced in utero on lung growth and function in an ovine model.

Methods: A CWD was induced in utero at 70-75 days of gestation in 14 ovine fetuses by resection of the 7th and 8th left ribs. Each non-operated twin fetus was taken as control. Respiratory mechanics was studied postnatally in the first week and at 1, 2, and 3 months. Post-mortem respiratory mechanics and lung histomorphometry were also assessed at 3 months.

Results: Eight out of 14 CWD lambs (57%) and 14 control lambs survived the postnatal period. One severe and five mild deformities were induced. At birth, inspiratory capacity (25 vs. 32 mL/kg in controls), and dynamic (1.4 vs. 1.8 mL/cmH2O/kg), and static (2.0 vs. 2.5 mL/cmH2O/kg) respiratory system compliances were decreased in CWD lambs. Apart from a slight decrease in inspiratory capacity at 1 month of life, no other differences were observed in respiratory mechanics measured in vivo thereafter. Postmortem measurements found a significant decrease in lung compliance-for each lung and for both lungs taken together-in CWD lambs. No differences in lung histology were detected at 3 months in CWD animals compared to controls.

Conclusions: Our study is the first to assess the effects of a prenatally induced CWD on lung development and function from birth to 3 months in an ovine model. Our results show no significant differences in lung histomorphometry at 3 months in CWD lambs compared to controls. Resolution at 1 month of the alterations in respiratory mechanics present at birth may be related to the challenge in inducing severe deformities.

Keywords: deformity; development; growth; in vivo model; pre‐clinical models.

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Conflict of interest statement

Jesse Shen has received traveling fellowship support from the Scoliosis Research Society. Nathalie Samson, Jérôme Lamontagne‐Proulx, Denis Soulet, Yves Tremblay, Charlène Nadeau, Sarah Bouchard, Marc Bazin, Jean‐Paul Praud declare that they have no conflict of interest. Stefan Parent has received royalties from EOS imaging, he is Co‐founder of the company Spinologics Inc., he received consultancy fees from K2M, Medtronic, and DePuy Synthes Spine, he received grants from DePuy Synthes Spine, Canadian Institutes of Health Research, Pediatric Orthopaedic Society of North America, Scoliosis Research Society, Medtronic, EOS imaging, Canadian Foundation for Innovation, Setting Scoliosis Straight Foundation, Natural Sciences and Engineering Council of Canada, Fonds de recherche Québec ‐ Santé, grants and Orthopaedic Research and Education Foundation, he received fellowship support from DePuy Synthes and Medtronic, he is the holder of the Academic Chair in Pediatric Spinal Deformities of CHU Ste‐Justine, he is member of speaker bureau of Orthopaediatrics.

Figures

FIGURE 1
FIGURE 1
Summary of chest wall measurements: spine to sternum (1) and spine to xyphoid (2) lengths, and rib cage width (3).
FIGURE 2
FIGURE 2
Representative scan of a control lamb's lung section used for histomorphometric analysis. Scale bar: 50 μm.
FIGURE 3
FIGURE 3
CT 3D reconstruction of the rib cage of a control lamb compared to a severe deformity lamb. (A) CT scans of control lamb, (B) CT 3D reconstruction of the rib cage of a control lamb, (C) CT scans of a deformity lamb, (D) CT 3D reconstruction of the rib cage of a deformity lamb.
FIGURE 4
FIGURE 4
Histograms of alveolar complexity analysis, measured as the perimeter/area ratio of closed structures. Various regions of the lungs were used for this histomorphometric analysis in control (n = 6) and CWD (n = 8) lambs. L, left; A, anterior; I, inferior; M, middle, P, posterior; R, right; S, superior, T, tracheal.

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