Research Recipients

Research Award Details

2015 - Angela S.M. Kuo Memorial Award

The Effect of Risser Body Casts on the Growth and Development of the Spine, Thorax and Lungs Using Immature Rabbit Model

Grant Recipient: Michael Glotzbecker, MD

Co-Investigators: Brian Snyder, MD,PhD

Institution:: Beth Israel Deaconess Med. Ctr., Boston

Presentations & Publications:: Plan for ICEOS, SRS, POSNA 2021 meeting submission

Further Funding:: We received concurrently a grant through CSSG (PSSG) that will allow completion of the project.

Additional Information:: Research findings:
Creating the model proved to be more challenging than expected. We encountered a number of issues creating a model that was safe for the animal subjects. This led to an extended period of trial and error before we could create experimental models. Initially we used a full cast. This proved to be heavy to allow adequate rabbit movement. We created a lighter cast/brace hybrid, but this proved challenging as it did not account for normal rabbit lumbar kyphosis which is required to position the rear legs properly to allow efficient movement. Also even with the lighter cast, this still led to the rabbits occasionally falling over. When doing so, they could not right themselves. Therefore we spent an extended time creating and machining a pulley system that could be connected to cast/brace to keep them upright. Finally, we settled on creating lightweight brace without fiberglass as the final model. This took time to create, as we needed multiple sizes that could be rapidly changed given the rapid rabbit growth rate. Ultimately we overcame these challenges and could institute our protocol and preliminary results follow. We appreciate POSNA and the POSNA research committees patience and extensions as we worked through this model.

A total of six of the 24 prepubertal New Zealand White Rabbits (5-weeks-old) were randomly assigned to one-of-three study arms (power analysis: N=8 per group) over a period of two years (2019-ongoing): cast/brace intervention without spinal deformity (I⁺D^-), cast/brace intervention with spinal deformity (I⁺D⁺), or age-sex matched control without any intervention (I^-D^-). Three rabbits received a straight brace (I⁺D^-) at 6-weeks until cessation of expected growth at 28-weeks, as previously described. The remaining three rabbits did not undergo casting or bracing and served as controls (I^-D^-). Sequentially larger braces were applied at 3-4-week intervals or until the rabbits outgrew the brace.

Pulmonary function was assessed using computed tomography (CT) with three-dimensional lung volume segmentation at 10- and 14 weeks. Unfortunately, the final 28-week CT scan and second group of six rabbits were scheduled but could not be performed due to the COVID-19 pandemic. Each series of CT scans consisted of three sequences: 1) ventilator-assisted ventilation representing normal tidal volume (settings: respiratory rate=15/min with 75_ml), 2) total lung capacity (TLC, breath hold at 25_cm H₂0 or maximal inspiration), and 3) functional residual capacity (FRC, breath hold at 0_cm H₂0 or maximal expiration). Post-mortem histopathologic analysis will be performed at 28-weeks to evaluate bronchopulmonary and alveolar architecture. Groups will be compared using an ANOVA with post-hoc pair-wise comparison of group means.

Preliminary data was available for the first rabbit cohort (N=6) during the creation of this report. Straight-braced rabbits had appropriate weight gain; however, the rate of increase was lower than corresponding control rabbits. Straight braced rabbits had reduced TLC at 10-weeks (mean, 47.1 cm³ vs. 58.4 cm³) and 14-weeks (mean, 52.3 cm³ vs. 60.2 cm³), whereas FRC was increased at 10-weeks (mean, 28.0 cm³vs. 19.0 cm³). At 14-weeks, straight braced rabbits had less FRC compared to control rabbits (mean, 25.8 cm³ vs. 35.2 cm³). Similarly, total lung mass (determined as 18.6% of total lung volume, in grams) was reduced at 10-weeks (mean, 10.8g vs. 13.3g) and 14-weeks (12.0g vs. 13.8g). In the intervention group, CT scans were performed while in-brace and immediately after brace removal. Differences were found for TLC and FRC before and after brace removal: 10-week TLC (39.7 cm³ vs. 47.1 cm³), 14-week TLC (50.0 cm³ vs. 52.3 cm³), 10-week FRC (21.6 cm³ vs. 28.0 cm³), and 14-week FRC (23.6 cm³vs. 25.8 cm³).

Complications included: 1) the pharyngeal anatomy of 10-week old rabbits was too small for the smallest size cuffed endotracheal tube (2.5 mm) which resulted in air leaks and inability to inflate to 25_cm H₂0 for maximal inspiration and evaluation of TLC in some cases; and 2) one rabbit developed a leg wound due to chronic brace irritation which required temporary brace removal.

Our data suggests that management with bracing reduces optimal lung development even in the absence of spinal deformity. However, the COVID-19 pandemic prevented completion of the study. Our final results will determine the true impact of thoracolumbar orthotic treatment in immature rabbits after comparison of histologic lung samples in control rabbits, straight braced rabbits, and rabbits with spinal deformity.