Olson J Casey, Takahashi Ayuko, Glotzbecker Michael P, Snyder Brian D
Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America; Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America.
PLoS One. 2015 Aug 28;10(8):e0136941. doi: 10.1371/journal.pone.0136941. eCollection 2015.
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.
与同等严重程度的青少年脊柱和胸壁畸形相比,脊柱和胸壁的早发性畸形(发病年龄小于8岁)与成年期发病率增加有关。据推测,在肺泡化后期对胸廓生长的抑制会导致肺生长和胸廓功能的不可逆丧失;然而,这种疾病从发病到成年的自然病程尚未得到很好的描述。在本研究中,我们建立了早发性脊柱侧凸的兔模型,以确定胸廓畸形对呼吸结构和功能发育的影响程度。通过手术右侧单根肋骨束缚术,在10只新西兰幼兔(3周龄)中诱导早发性脊柱侧凸伴肋骨融合。通过纵向屏气计算机断层扫描成像跟踪脊柱畸形的进展、功能残气量、肺总量和肺质量,直至骨骼成熟(28周龄)。此外,在成熟时计算用力肺活量和区域比容作为功能测量指标,并进行组织形态计量学分析,以放射状肺泡计数作为腺泡复杂性的指标。将肋骨束缚兔的数据与年龄匹配的健康对照兔(N = 8)进行比较。结果显示,单侧肋骨束缚导致脊柱畸形逐渐发展,曲率范围为30°至120°,其严重程度与肺生长和功能结果密切相关。在成熟时,畸形大于中位数(55°)的兔子体重下降(89%),右肺(59%)和左肺(86%)质量下降,右肺(74%)和左肺(69%)放射状肺泡计数下降,右肺在肺总量时的体积(60%)和用力肺活量(75%)下降。儿童脊柱畸形的早期治疗可能预防成年期的肺部并发症,这些结果为根据胸廓结构预测肺发育提供了依据。该模型未来也可能用作评估治疗效果的平台。