, Volume 469, Issue 5, pp 1375-1382,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 22 Mar 2011

Expansion Thoracoplasty Affects Lung Growth and Morphology in a Rabbit Model: A Pilot Study

Abstract

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.

Clinical Relevance

Creating an animal model for thoracic insufficiency syndrome should provide insight into the effect of expansion thoracoplasty on lung development otherwise clinically unattainable.

The institution of one or more of the authors (BDS) has received funding from the Scoliosis Research Society, the Chest Wall and Spine Deformity Study Group, Synthes Spine (West Chester, PA), and the National Institutes of Health (Grant Number 1R21AR057880-01).
Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at Beth Israel Deaconess Medical Center and Children’s Hospital.