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

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.

Expansion thoracoplasty affects lung growth and morphology in a rabbit model: a pilot study.

BACKGROUND: Thoracic insufficiency syndrome represents a novel form of postnatal restrictive respiratory disease occurring in children with early-onset scoliosis and chest wall anomalies. Expansion thoracoplasty improves lung volumes in children with thoracic insufficiency syndrome; however, how it affects lung development is unknown. QUESTIONS/PURPOSES: Using a rabbit model of thoracic insufficiency syndrome, we evaluated the effect of expansion thoracoplasty on the response of biologic mechanisms in the alveolar microstructure. METHODS: Using archived material from a previous experiment, 10 4-week-old New Zealand rabbits were divided into three groups: normal (n = 3), disease (n = 3), and treated (n = 4). Left ribs four to eight were tethered in seven rabbits at age 5 weeks to induce hypoplasia of the left hemithorax (disease). At age 10 weeks, four of these rabbits were treated by expansion thoracoplasty (treated). At age 24 weeks, lungs were excised and processed. Alveolar density and parenchymal airspace were measured on histologic sections. Immunohistochemistry was performed for vascular endothelial growth factor receptor 2 (angiogenesis), KI-67 (cell proliferation), and RAM-11 (macrophages). RESULTS: Alveolar walls were poorly perfused and airspace fraction was larger (emphysematous) in disease rabbits than normal or treated rabbits. Immunohistochemistry provided inconclusive evidence to support the concept that pulmonary hypoplasia is induced by thoracic insufficiency syndrome and controlled by expansion thoracoplasty. CONCLUSIONS: Treatment of thoracic insufficiency syndrome by expansion thoracoplasty may prevent emphysematous changes in the alveolar microstructure, thereby enhancing gas exchange.

Expansion thoracoplasty improves respiratory function in a rabbit model of postnatal pulmonary hypoplasia: a pilot study.

STUDY DESIGN: Using a rabbit model of postnatal pulmonary hypoplasia, we investigated how expansion thoracoplasty affected growth of the spine and lungs. OBJECTIVE: By constricting the hemithorax in a growing rabbit to create postnatal pulmonary hypoplasia, we quantified how expansion thoracoplasty affects lung volume, respiratory function, alveolar morphology, and spine growth. SUMMARY OF BACKGROUND DATA: In children with thoracic insufficiency syndrome, expansion thoracoplasty of the constricted hemithorax improves respiratory function and controls scoliosis. We hypothesize that expansion thoracoplasty of the constricted hemithorax improves pulmonary hypoplasia by allowing the lung to expand, improving respiratory function and stimulating lung growth. METHODS: Postnatal pulmonary hypoplasia and scoliosis were induced in 5-week old rabbits by constricting left ribs 3 to 8. Expansion thoracoplasty through the fused ribs was performed at 10 weeks. These were compared with Disease rabbits allowed to grow with a constricted left hemithorax and Normal rabbits. Spine and thoracic deformity, right and left lung volumes were measured on reconstructed 3-dimensional computed tomography images and functional residual capacity measured by plethysmography. At maturity, lungs were excised and quantitative histology performed to measure alveolar air fraction and surface density. RESULTS: Expansion thoracoplasty of the constricted left hemithorax improved scoliosis but increased left lung volumes only moderately compared with Disease rabbits. For Disease and Thoracoplasty Treated rabbits, a compensatory increase in the volume of the right lung maintained total lung volumes equivalent to Normal. Alveolar air space fraction was greater in Disease rabbits, suggestive of emphysema improved by expansion thoracoplasty. Capillaries adjacent to the alveoli were prominent in Thoracoplasty Treated rabbits. CONCLUSION: Expansion thoracoplasty reduces scoliosis and increases the volume of the constricted hemithorax, but the relative increase in the ipsilateral lung volume is small since compensatory hypertrophy of the contralateral lung also occurred. Expansion thoracoplasty may improve respiratory function by increasing alveolar capillaries and preventing emphysematous changes.

The reciprocal relationship between thoracic and spinal deformity and its effect on pulmonary function in a rabbit model: a pilot study.

STUDY DESIGN: Investigate the association between growth of the spine and thorax under conditions that create symmetric or asymmetric growth disturbances of the spine or thorax in a growing rabbit. OBJECTIVE: Prove growth of the spine and growth of the thorax are directly related. SUMMARY OF BACKGROUND DATA: Understanding the association between growth of the thorax and growth of the spine may explain the occurrence of thoracic insufficiency in patients with congenital scoliosis. METHODS: Symmetric or asymmetric growth disturbances of the spine or thorax were established in 5-week-old rabbits. During growth of the rabbits, structural changes in the spine, thorax, and lung volume were assessed using serial CT scans. Measures of pulmonary function, spine, and thoracic deformity were related to one another across groups. RESULTS: The mean Cobb angle and distortion of the thoracic cage were significantly greater for the unilateral tethered rib group. There were no significant differences in total lung volume among the experimental groups. However, the left/right lung volume ratio was significantly different for the unilateral tethered rib group compared with the control group. CONCLUSIONS: Unilateral deformity of the spine or thorax induces both a scoliosis and thoracic cage deformity with asymmetric lung volumes.