Aerosol Ventilation for Rapid Cooling of Transplant Donor Lungs

项目总结

PROJECT SUMMARY Over 2,700 lung transplants are performed in the US each year, but a significant shortage of donor lungs means that thousands of people die each year while waiting for a suitable donor organ. Although most donor lungs in the US are currently taken from brain-dead donors, only ~20% of multiorgan brain dead donors provide suitable lungs for transplantation. A significant opportunity for more donor lungs lies with donation after cardiac death (DCD) donors, but only a tiny fraction of DCD donors in the US are used for lung transplantation due to concerns over ischemic damage. Lungs are considered significantly injured from warm ischemia if they are not cooled and oxygenated within 60–90 min of diminished perfusion or oxygenation. In addition, lungs from DCD donors subject to warm ischemia for >60 min prior to procurement have impaired bronchial healing and greater risk of primary graft dysfunction or reperfusion injury. As such, developing a simple and non-invasive method of cooling and oxygenating lungs in potential uncontrolled DCD donors would mitigate the damaging effects of warm ischemia while the donor is prepared for procurement and provide a boundless supply of lung donors from this untapped donor pool. To improve the pool of usable donor lungs, Boundless Science, LLC developed a bi-liquid aerosolized ventilation (BAV) device prototype that cools a lung quickly and efficiently following death. The BAV aerosolizes a mixture of two liquid perfluorocarbons (LP), introduces the atomized droplets into the lungs through a ventilator or mask, collects evaporated LP vapors from the lungs, condenses and oxygenates the vapor, and returns the cooled LP liquid to the lungs via the original aerosolization method. The LP’s enthalpy of vaporization provides rapid cooling while its ability to carry oxygen prevents hypoxic lung damage. This safe, easy-to-use, portable device is ambulatory and can be used in the ICU and the ER to non-invasively cool and oxygenate lungs for transplant well within an hour after death. The objective of this phase 1 proposal is to provide proof of concept that lungs can be efficiently cooled from 37°C to 20°C (to decrease metabolic consumption by the lungs while providing oxygen to the airways) in <30 min using a combination of LPs. To achieve efficient cooling with BAV, we believe that we need to incorporate the following optimized parameters: droplet size and their alveolar dwell time, boiling point of the LP mixture, and heat transfer fluid. This will be achieved using four Specific Aims. Aim 1: Create the optimal droplet size and density to effectively infiltrate alveoli with aerosolized Perfluoropentane. Aim 2: Build and evaluate an exhaled cooling system to recover the vaporized LP. Aim 3: Determine the optimized mixture of LPs and a clinically relevant cooling method such that pig lungs can be cooled by 17°C (to 20°C) in under 30 minutes using optimized BAV parameters. Aim 4: Modify ventilator settings to manipulate the alveolar dwell time of LP droplets. Once proof of concept has been obtained, we will progress to Phase II, where we will refine our prototype device, test it on live animals and test for tissue health, and pursue FDA approval.