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Development of Rabbit Model for Thoracic Insufficiency Syndrome: Clinical Implications for Treatment
Start Date: 2/26/2016Start Time: 4:00 PM
End Date: 2/26/2016End Time: 5:30 PM
Event Description
BIOMED Seminar

Title:
Development of Rabbit Model for Thoracic Insufficiency Syndrome: Clinical Implications for Treatment

Speaker:
Brian D. Snyder, MD, PhD
Professor of Orthopaedic Surgery
Harvard Medical School
Research Professor, Department of Bioengineering
Boston University
Director, Cerebral Palsy Clinic
Boston Children's Hospital

Details:
Anomalies affecting the growth and development of the spine and/or ribs in growing children severely impact respiratory function, however the relationship between respiratory function and structural deformities of the thorax during growth is not well understood. The objective of this study was to create an animal model that develops severe thoracic deformity early in life so as to evaluate the resulting influence on the growth, structure and function of the spine, thorax and lungs. Therefore we tethered the right rib cage of 3.5-week old rabbits to provoke progressive constriction of the thorax during skeletal growth to limit the space available for the lung to grow, distort the spine and diaphragm, and alter chest wall compliance.

We tested the hypotheses: 1) structural deformities that limit the growth of the spine and thorax during development of the lung, spine and rib cage provoke mechanical inhibition of respiration and induce postnatal pulmonary hypoplasia sufficient to degrade respiratory function at skeletal maturity; 2) the extent of deformity of the spine and thorax during growth predicts respiratory function at skeletal maturity; 3) reversal of thoracic constriction by expansion thoracoplasty will improve growth of the spine, rib cage, and lung in proportion to the growth potential remaining for these structures.

To accomplish our aims, computed tomography (CT)
imaging of the thorax was performed at regular intervals
throughout growth until maturity to monitor progressive
deformity of the spine and rib cage and measure aerated lung volumes at known inspiratory pressures. From reconstructed 3D CT images of the entire thorax, the functional residual capacity (FRC), total lung capacity (TLC), and elastance of the lung and thorax were determined. By comparing static changes in thoracic anatomy and dynamic changes in respiratory mechanics measured in rabbits with a tethered hemithorax vs. normal control rabbits, we demonstrated that deformities of the spine and thorax acquired at an early age mechanically inhibited lung growth and restricted respiratory function, supporting our first hypothesis. Additionally we demonstrated that the extent of spinal deformity present during growth (at 6 weeks of age) predicted the extent of thoracic deformity and degradation in respiratory function at adulthood (28 weeks), supporting our second hypothesis.

These results lend credence to the clinical concept that early treatment of spinal deformity in children will prevent pulmonary complications in adulthood. To our knowledge this is the first animal model created to simulate early onset thoracic deformity for the purpose of serially evaluating pulmonary growth and function.

For more info, please visit drexel.edu/biomed.

WATCH WEBCAST

Biosketch:
Brian D. Snyder, MD, PhD, is Professor of Orthopaedic Surgery, Harvard Medical School and Research Professor of Bioengineering at Boston University, Department of Bioengineering.  An attending orthopaedic surgeon at Boston Children’s Hospital, he directs the Cerebral Palsy program; his clinical practice focuses on congenital and acquired deformities about the hip and spine related to neuromuscular conditions as well as pediatric trauma. As a clinician-scientist funded by NIH, DoD and OREF, his translational research focuses on improving the practice of orthopaedic surgery by applying engineering principles to solve clinical problems. Using principles of structural engineering to analyze computed tomographic images of skeletal metastases, he developed a non-invasive method to accurately predict pathological fractures in cancer patients, thereby providing a mechanical assay of bone health that is now being used to optimize orthopaedic treatment in clinical trials. In recognition for this work, Dr. Snyder received a Kappa Delta Award from the American Academy of Orthopaedic Surgeons.

Dr. Snyder also developed an animal model for Thoracic Insufficiency Syndrome, a disease where congenital deformity of the spine and thorax suppress lung growth in children. This model has been used to parametrically evaluate and compare emerging treatment protocols for this fatal syndrome. The Scoliosis Research Society acknowledged this work with the Russell Hibbs Award. Additionally his group derived a novel dual ultrasound system to non-invasively measure real time cervical spine kinematics and intervertebral disc deformation during extreme activities as well as developed novel contrast agents for computed tomography and MRI imaging to evaluate the in-vivo biochemical and biomechanical properties of hyaline cartilage in synovial joints affected by traumatic or osteoarthritis. In recognition for training students and physicians in applied biomechanics and translational research, he was awarded the A. Clifford Barger Excellence in Mentoring Award from Harvard Medical School.
Contact Information:
Name: Ken Barbee
Phone: 215-895-1335
Email: barbee@drexel.edu
Dr. Brian D. Snyder
Location:
Papadakis Integrated Sciences Building (PISB), Room 120, located on the northeast corner of 33rd and Chestnut Streets.
Audience:
  • Undergraduate Students
  • Graduate Students
  • Faculty
  • Staff
  • Special Features:
  • Online Access

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