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

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.

Expansion Thoracoplasty in Rabbit Model

“…Study time points are outlined in Figure 1. Control data from 10 Disease rabbits with untreated rib fusion with scoliosis and 8 Normal rabbits was previously published 21 .…”

“…Rib tethering was performed on Disease control, Early treatment, and Late treatment rabbits at 3 weeks of age. This was previously described in detail 21 .…”

“…Rabbits were positioned prone and 2 scans acquired during respiratory breath-holds of 0 and 25 cm H 2 O pressure, these scans are representative of functional residual capacity (FRC) and total lung capacity (TLC) respectively. Maximal spine deformity angle (θ M ), thoracic rotation angle (TRA), left and right lung aerated volume at FRC and TLC, left and right lung mass, and fractional tissue volume (FTV) were measured as previously described 21 . For ET rabbits, the length of the distraction between hooks was also measured from CT.…”

“…Previously, our group developed a rabbit model of TIS from surgically induced rib fusion producing an associated scoliosis in which extent of detriment to respiratory growth and function at maturity was highly predictable based on severity of the induced spine curve 21 . The objective currently is to use this disease model as a testing platform to evaluate respiratory development after one particular growth sparing treatment; expansion thoracoplasty (ET) distraction.…”

Clinical Issues for Pediatric Pulmonologists Managing Children With Thoracic Insufficiency Syndrome

“…It is unknown if the diaphragm muscle fibers per se are atrophied or adapt to chronic mechanical loads. In animal models of EOS produced early in life, the diaphragms in adulthood have reduced cross-sectional surface area ( 24 ).…”