(I-338) Utilization of Thermoelectric Cooling to Achieve Hypothermic Regulation of Donor Organs During Transport

Introduction:: Lung transplantation remains the only definitive treatment for end-stage lung disease, but it remains constrained by a lack of donor organs. One strategy to increase the donor supply is to optimize the utilization of donated lungs, improve post-transplant outcomes, and maximize graft longevity. Organ preservation and transport techniques are increasingly recognized as a key step in this process. The current gold standard for lung preservation and storage involves a cooler and ice (2 to 4 C). However, recent research has demonstrated the risk of cold ischemic injury with this approach which can lead to mitochondrial dysfunction and protein denaturation. Improving the technique to preserve, store, and transport lungs allografts has the potential to improve organ quality, patient outcomes, and prolong the maximum allograft ischemic time.

Here we present a novel solution to maintain lungs at an optimal temperature of 10 C utilizing a thermoelectric cooling unit in a custom enclosure, with integrated temperature controllers and sensors. Our solution utilizes a pump that provides continuous active cooling, has feedback-regulated temperature control, and is designed to be reusable by accommodating the standard three-bag organ technique used during procurement to maintain sterilization.

This new storage device represents an advance in lung preservation, offering a more efficient and effective method for donor lung preservation. Additionally, this method offers substantial cost savings over other commercial perfusion devices and may lead to increased access to transplantation and improved patient outcomes.


Materials and Methods:: Design: Temperature modulation was enabled using a thermoelectric cooler unit (Custom Thermoelectric). A cooling power of 50 watts enabled temperatures 20 degrees Celsius below ambient temperature. To pump water to the enclosure, a peristaltic pump with 3/8" inlets and outlets was utilized.

To control and monitor the temperature inside the enclosure, a custom temperature controller using an Arduino Uno, 10k thermistors, and an LCD display was used. The controller utilizes pulse width modulation (PWM) and proportional-integral-derivative (PID) feedback to maintain a water temperature of 10 degrees Celsius. The enclosure was constructed using 1/8" aluminum for outer housing to optimize durability and minimize weight. The inner housing was made from 1/16" aluminum and Styrofoam . The TEC's and controllers were mounted outside of the box, and an additional enclosure was mounted at the bottom to house the 100 AH battery, and charging unit.

Validation: Swine lung blocks (n=6) were explanted in standard fashion. Lungs were split with one lung stored on ice, and one in thermoelectric cooling unit for a period of 8 hours. For the TEC unit each lung was triple bagged, and a temperature probe was placed in the second bag to maintain sterility. The lungs were completely submerged in water, and the system was allowed to run for an eight-hour period. Data collected during this included continuous organ and ambient temperature, thermography and time-lapse photography, and tissue samples for histopathologic review. Tissue samples were taken immediately following explant, after four hours, and at the conclusion of the experiment.


Results, Conclusions, and Discussions:: Continuous temperature recording with the thermoelectric device revealed excellent maintenance of organ temperature (n=6) at 10 C ± 0.9 degrees. Lungs procured in standard fashion, with cold flush and topical hypothermic cooling, took on average 15.6 min to reach 10 C within our device. Lungs stored on ice in standard fashion were maintained at much lower temperatures (range: 1.2 – 4.5 C). Thermography demonstrated even and consistent surface cooling in lungs stored at 10 C utilizing thermoelectric circulation, whereas lungs stored on ice appeared much more heterogenous temperature distribution with areas in direct contact with ice being much cooler than areas exposed to ambient air.

After 8 hours of preservation tissue integrity and cellular viability was evaluated with detailed histology, and TUNEL and CASPACE staining. Lungs maintained at 10 C demonstrated significantly less cell death pathway activation and had improved architecture with minimal alveolar edema and interstitial thickening.

Additional validation and experimentation are currently underway. These includes blinded pathologic review with validated lung injury scores. Analysis of bronchoalveolar lavage prior to procurement and at the conclusion of preservation to analyze markers of inflammation and metabolism. Lastly, following preservation, lungs will be mounted on ex-vivo perfusion to analyze lung function, gas exchange, and compliance.

In conclusion, our findings suggest that our thermoelectric cooler represents a more efficient and effective method for donor lung preservation, with the potential to improve the quality of donor lungs upon delivery and subsequently improve patient outcomes. Furthermore, our results highlight the importance of utilizing advanced preservation techniques to limit cold ischemic injury, preserve mitochondrial function, maximize cellular viability, and ultimately lead to better outcomes for lung transplant recipients.


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