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 vivo and 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.
- Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model – Saito, M. et al. Journal of Thoracic and Cardiovascular Surgery. 2018.
- Inhibition of B cell–dependent lymphoid follicle formation prevents lymphocytic bronchiolitis after lung transplantation – Smirnova, N. F. et al. JCI Insight. 4(3). 2019.
- Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease – Keeler, A. M. et al. Human Gene Therapy, 30(1), pp. 57–68. 2019.
- Effects of Warm Versus Cold Ischemic Donor Lung Preservation on the Underlying Mechanisms of Injuries during Ischemia and Reperfusion – Iskender, I., et al. Transplantation, 102(5), 760–768. 2018.
- Impact of different intratracheal flows during lung decellularization on extracellular matrix composition and mechanics – Bellezzia, M. A., et al. Regenerative Medicine, 13(5), 519–530. 2018.
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.
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