Over 2,700 lung transplants are performed in the US each year, but a significant shortage ofdonor lungs means that thousands of people die each year while waiting for a suitable donororgan. 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 significantopportunity for more donor lungs lies with donation after cardiac death (DCD) donors, but only atiny fraction of DCD donors in the US are used for lung transplantation due to concerns overischemic damage. Lungs are considered significantly injured from warm ischemia if they are notcooled 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 haveimpaired bronchial healing and greater risk of primary graft dysfunction or reperfusion injury. Assuch, developing a simple and non-invasive method of cooling and oxygenating lungs inpotential uncontrolled DCD donors would mitigate the damaging effects of warm ischemia whilethe donor is prepared for procurement and provide a boundless supply of lung donors from thisuntapped donor pool.To improve the pool of usable donor lungs, Boundless Science, LLC developed a bi-liquidaerosolized ventilation (BAV) device prototype that cools a lung quickly and efficiently followingdeath. The BAV aerosolizes a mixture of two liquid perfluorocarbons (LP), introduces theatomized droplets into the lungs through a ventilator or mask, collects evaporated LP vaporsfrom the lungs, condenses and oxygenates the vapor, and returns the cooled LP liquid to thelungs via the original aerosolization method. The LP's enthalpy of vaporization provides rapidcooling 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 andoxygenate 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 efficientlycooled from 37°C to 20°C (to decrease metabolic consumption by the lungs while providingoxygen to the airways) in <30 min using a combination of LPs. To achieve efficient cooling withBAV, we believe that we need to incorporate the following optimized parameters: droplet sizeand their alveolar dwell time, boiling point of the LP mixture, and heat transfer fluid. This will beachieved using four Specific Aims. Aim 1: Create the optimal droplet size and density toeffectively infiltrate alveoli with aerosolized Perfluoropentane. Aim 2: Build and evaluate anexhaled cooling system to recover the vaporized LP. Aim 3: Determine the optimized mixture ofLPs and a clinically relevant cooling method such that pig lungs can be cooled by 17°C (to20°C) in under 30 minutes using optimized BAV parameters. Aim 4: Modify ventilator settings tomanipulate the alveolar dwell time of LP droplets. Once proof of concept has been obtained, wewill progress to Phase II, where we will refine our prototype device, test it on live animals andtest for tissue health, and pursue FDA approval.
Public Health Relevance Statement: PROJECT NARRATIVE
Thousand of patients die each year while waiting for a lung transplant because of a scarcity of suitable donor
lungs, in part because of the challenges associated with the rapid cooling and oxygenation necessary to
prevent transplant-preventing lung injury after the death of a potential donor. To solve this issue, we have
developed a system (termed bi-liquid aerosolized ventilation device) to efficiently and rapidly cool and
oxygenate lungs before any damage occurs, thereby having the potential to significantly increase the pool of
donor lungs. Our portable device is safe, easy-to-use, and 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.
Project Terms:
