Organ Transplant & Regeneration
The prevalence of lung transplants has increased over the past 30 years as it has become a practical option for numerous lung diseases, doubling over the past decade. One of the main limiting factors to lung transplants is the viability of the transplanted lung, with only 15% of donor lungs being harvested in contrast to hearts harvested at 30% and livers and kidneys at 80%.
Harvested lungs are susceptible to trauma in death and during transport and handling, with high incidences of infection, pneumonia and ventilator-induced lung injury (VILI) once implanted. These sensitivities necessitate better screening of the lungs in vivoand ex vivo and careful monitoring following a successful transplant.
ADVANCED LUNG FUNCTION MEASUREMENTS.
The flexiVent provides many tools to implement and test novel ventilation and conditioning patterns for the transplanted lungs. By providing computer-controlled piston ventilation, the system can vary the parameters of the ventilation to mitigate VILI and test therapeutic transplant ventilation patterns. Additional maneuvers including Deep Inflation allow the lung to be inflated to physiological total lung capacity (TLC – 30 cmH2O) to improve air flow and reverse airway closure.
Detailed respiratory mechanics measurements can be used to gauge the improvement from donor lung implant, track the progression of the recovery using longitudinal studies, measure the inflammation and stiffness changes and further partition these outcomes between the central and lower airways.
- The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation. – Weber et al. Sci Transl Med., 6(252):252ra124, 2014.
- Protective role of T-bet and Th1 cytokines in pulmonary graft-versus-host disease and peribronchiolar fibrosis. – Gowdy et al. Am J Respir Cell Mol Biol., 46(2):249, 2012.
- An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes. – Cardoso et al. J Bras Pneumol., 37(5):589, 2011.
LONGITUDINAL MEASUREMENTS IN CONSCIOUS SUBJECTS.
Once the host has received a lung transplant or cell graft, changes in ventilatory mechanics can reflect the recovery period. The ability to repeatedly follow conscious models, provides valuable insight into the overall improvement of the host and detection of rejection or common associated pulmonary disorders. Changes in the breathing pattern and ventilatory outcomes can correlate with acute host rejection, a primary risk factor for morbidity and mortality.
- Both hemopoietic and resident cells are required for MyD88-dependent pulmonary inflammatory response to inhaled endotoxin. – Noulin et al. J Immunol., 175:6861, 2005.
- BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation. – Medoff et al. J Exp Med. 202(1):97, 2005.