IP Requirement: Medical University of South Carolina IP

Experience Requirement:

– Mechanical Design

– Rapid Prototyping

Lung transplantation is the only durable treatment for end stage lung disease.  Unfortunately, two major issues continue to vex the transplant community – 1) the number of waitlist recipients far outpaces the number of suitable donor offers, leading to significant waitlist mortality, and 2) primary graft dysfunction, which leads increased 90-day and 1-year mortality, and is significant cause of chronic lung allograft dysfunction.  

A recent change to the donor allocation system has resulted in transplant centers traveling farther for donors, with resultant increases in ischemia time.  Traditionally, two options exist for lung recovery – cold static storage after perfusion with a low-potassium, dextran-based preservation solution, or normothermic ex-vivo lung perfusion (EVLP).  The former affords the benefit of low cost and simplicity while the latter may increase the donor pool by allowing perfusion with diuretics and/or antibiotics potentially allowing for use or marginal donors.   Unfortunately, specialized training is required, and the durable goods required for EVLP are expensive.  Additional solutions to donor recovery are needed.  

Recently, studies have shown that storage at 10o Celsius may extend ischemia time and improve the function of statically stored donor lungs.  A secondary benefit – demonstrated in a clinical trial – of extending the cold ischemia time using 10o static storage has been turning lung transplant into an “elective” operation, with decreased rates of primary graft dysfunction at 72 hours. The cellular mechanism has been incompletely explored, however, improved mitochondrial health serves the putative mechanism. We believe the next logical step is the addition of ventilation to the stored lungs.  Our preliminary data in an ex-vivo murine model demonstrates improved pulmonary compliance (fig. 1), decreased lung injury (fig. 2) , increased cellular viability (fig. 3) and further improvements in mitochondrial health (fig. 4) when adding ventilation to cold static storage at 10o Celsius.  These data indicate that cyclic parenchymal stretch may have further protective effects on the stored lung.  

Our specific hypothesis is that cyclic parenchymal stretch (ventilation) is associated with improved function on the cellular level in cold static storage.  This improved function will allow for further increases in cold ischemia time, and decreased rates of primary graft dysfunction after implantation.  A predication of this specific hypothesis is that cyclic parenchymal stretch will improve mitochondrial biogenesis, which in turn will decrease apoptotic signaling. This improved mitochondrial health will result in improved lung function after transplantation.  

We propose the development of a novel storage device that will allow for easy transport of donor lungs, with immediate implementation of 10o Celsius static storage, coupled with ventilation of the lung (e.g. a ventilator cooler).  This device will require no specialized training for recovery surgical teams, and will be capable of storing donor lungs for 24 hours at 10o Celsius.  

The immediate impact of this device will be the ability to increase cold ischemia time and improve transplanted graft function.  This device will be studied in an ex-vivo donor model – namely recovery of non-allocated donor lungs – where we will aim to determine lung compliance, histologic evidence of lung injury, and assess cellular viability and mitochondrial health. We would further plan to use the device in a clinical trial to determine the effect of this storage method on transplanted lung outcomes, with the ultimate goal of developing a tool capable of expanding the donor pool by breaking distance barriers, and thus increase the number of lung transplants performed.