Expansion Thoracoplasty in Rabbit Model: Effect of Timing on Preserving Pulmonary Growth and Correcting Spine Deformity

Abstract

Study design: In a treatment-control animal study expansion thoracoplasty (ET) was performed in a juvenile rabbit model of thoracic insufficiency syndrome (TIS) and benefits to thoracic development and respiratory function quantified. Rabbits treated early versus late were compared to age-matched normal and disease control rabbits through to skeletal maturity.

Objective: Evaluate (1) how ET changes the natural TIS disease trajectory and (2) how timing of ET affects changes in spine growth, lung growth, and respiratory mechanics.

Summary of background data: Pulmonary growth potential is thought to diminish with age; thus, early therapeutic intervention may increase pulmonary growth in children with TIS. However, no direct empirical evidence exists to support this treatment paradigm.

Methods: Convex left scoliosis and resultant TIS was induced in 3-week-old rabbits via surgical rib tethering. We compare the efficacy of ET performed at 7 weeks and expanded at 11 weeks (early, n = 7) versus only at 11 weeks of age (late, n = 7) in preserving lung growth and respiratory function relative to normal (n = 8) and disease (n = 10) rabbits. Sequential computed tomography images and pulmonary function testing was performed to quantify spine curvature, lung growth, and respiratory volumes. At 28 weeks of age chest wall elastance was measured in vivo then acinar complexity analyzed histologically via radial alveolar counts.

Results: ET performed early or late altered the predicted trajectory of spine deformity, pulmonary growth inhibition, and respiratory dysfunction seen in disease rabbits. Growth was not significantly different between early and late rabbits and post-treatment gains remained below those of age-matched normal rabbits. Chest wall elastance was impaired by ET and more so in early rabbits, there were no differences in pulmonary elastance.

Conclusion: ET interrupted the natural progression of deformity and pulmonary hypoplasia associated with spine curvature in disease rabbits. However, growth benefits are only seen in cases of the most severe initial deformity and must be balanced against the further impairment to chest wall function associated with repetitive surgery.

Level of evidence: N/A.

Figure 1. Study Overview

Timing of surgeries, CT scans, and pulmonary function testing relative to postnatal age in each group.

Figure 2. Expansion Thoracoplasty Surgery

(A) Exposure of right rib mass; (B) Anterior to posterior fluoroscopy identifying apex of deformity; (C) Thoracostomy with distraction of interposed PEEK device.

Figure 3. CT Reconstructions

Posterior projections of spine, lungs and PEEK device (yellow) comparing Disease control (left) and Early treatment (right) rabbits at 28 weeks of age.

Figure 4. Progression of Spine Deformity

Maximal spine curvature (left) and thoracic rotation (right) at maturity in relation to severity of juvenile spine curvature (θ_M,6wk) for each experimental group. Linear regression is displayed for each group; treatment group means are shown by dashed lines and Disease group mean and 95% prediction bounds by unbroken lines. See online supplement Figure S2 for Disease group data points. Tx = treatment.

Figure 5. Lung mass

Total, left, and right lung mass at maturity for all experimental rabbits in relation to severity of juvenile spine curvature, correlation values are indicated. Average Normal values are indicated by the dotted horizontal line. Linear regression is displayed for each group; treatment group means are shown by dashed lines and Disease group mean and 95% prediction bounds by unbroken lines. See online supplement Figure S3 for Disease group data points. Tx = treatment.

Figure 6. Lung RAC

Total, left, and right lung RAC at maturity for all experimental rabbits in relation to severity of juvenile spine curvature, correlation values are indicated. Average Normal values are indicated by the dotted horizontal line. Linear regression is displayed for each group; treatment group means are shown by dashed lines and Disease group mean and 95% prediction bounds by unbroken lines. See online supplement Figure S4 for Disease group data points. Tx = treatment.

Figure 7. Respiratory Elastance

Progression of respiratory elastance (left) and Partitioned elastance at 28 weeks of age (right) for Normal and treated rabbits. Significant differences are indicated with p-values: *p<0.05, **p<0.01, ***p<0.001.