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. 2015 Aug 28;10(8):e0136941.
doi: 10.1371/journal.pone.0136941. eCollection 2015.

Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis

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Free PMC article

Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis

J Casey Olson et al. PLoS One. .
Free PMC article

Abstract

Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have future use as a platform to evaluate treatment effectiveness.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study overview.
Timing of surgery, CT scans, and respiratory mechanics testing relative to post-natal age of rabbits are indicated.
Fig 2
Fig 2. Tethering surgery.
Tethering ribs 3–9 comprising the right hemithorax: (A) longitudinal incision exposing ribs; (B) ribs constricted with blue vessel loop; (C) polyester suture tied off to maintain constriction of right hemithorax, vessel loop removed.
Fig 3
Fig 3. CT image reconstructions.
Reconstructions are from 28 week post-natal age demonstrating deformity of thorax and lungs of a representative (A) Normal, (B) Moderate, and (C) Severe rabbit. The inferior surface of the lungs is colored orange.
Fig 4
Fig 4. Deformity.
(A) Maximal overall spine deformity, θM, in each group at all time points and (B) TRA in each group for all time points are shown. Bonferroni statistical significance is indicated: *p<0.05; **p<0.01; ***p<0.001.
Fig 5
Fig 5. Progression of Deformity.
Linear regression comparing spine deformity at 6 weeks to 28 weeks post-natal age is shown.
Fig 6
Fig 6. Lung mass.
(A) Left and (B) right lungs mass at each time point is shown. Statistical significance is indicated: **p<0.01, ***p<0.001.
Fig 7
Fig 7. Respiratory elastance.
Dynamic elastance versus spine deformity, θM. Normal rabbits are indicated by circles, Moderate deformity by triangles, and Severe deformity by diamonds.
Fig 8
Fig 8. Local specific volume.
Comparison of image registration results between Normal (top row), Moderate (center) and Severe (bottom) rabbits. Column (A): coronal slice with the registration displacement map, magnitude and direction of displacements are indicated by yellow vectors. Column (B): axial slice with derived sVol map, hot colors indicate greater expansion and green neutral. Column (C): Comparison of regional sVol, posterior to anterior, between Normal, Severe, and Moderate rabbits at each phase of inspiration. Error bars show SD.
Fig 9
Fig 9. Radial alveolar count.
Alveolar histology of a representative (A) Normal and (B) Severe rabbit showing the radial alveolar count. A line is drawn from the center of the respiratory bronchiole perpendicular to the nearest interlobular septa, each saccule bisected by this line is counted.

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References

    1. Dimeglio A, Bonnel F. Le rachis en croissance Paris Berlin: Springer; 1990.
    1. Campbell RM Jr, Smith MD. Thoracic insufficiency syndrome and exotic scoliosis. J Bone Joint Surg Am. 2007;89 Suppl 1:108–22. Epub 2007/02/03. 10.2106/JBJS.F.00270 . - DOI - PubMed
    1. Dunnill MS. Postnatal growth of the lung. Thorax. 1962;17(4):329–33.
    1. Narayanan M, Owers-Bradley J, Beardsmore CS, Mada M, Ball I, Garipov R, et al. Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance. Am J Respir Crit Care Med. 2012;185(2):186–91. Epub 2011/11/11. 10.1164/rccm.201107-1348OC - DOI - PMC - PubMed
    1. Herring MJ, Putney LF, Wyatt G, Finkbeiner WE, Hyde DM. Growth of alveoli during postnatal development in humans based on stereological estimation. American journal of physiology Lung cellular and molecular physiology. 2014;307(4):L338–44. 10.1152/ajplung.00094.2014 - DOI - PMC - PubMed

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