This proof-of-concept study explores the feasibility and effectiveness of ex vivo lung perfusion (EVLP) in an orthostatic position, using an innovative adjustable dome designed to improve the preservation of lungs intended for transplantation. The research, conducted by a team led by Prof. Massimo Boffini at the University of Turin, addresses a crucial issue in the field of lung transplantation: optimizing organ preservation to increase the availability and quality of lung transplants.
The adjustable PerLungs® dome represents a significant innovation in the field of EVLP. This technology allows changing the position of the graft from 0° to 90° during the procedure, mimicking the physiological position of the lungs in a standing subject. The dome is equipped with a mobile support base that can be manually tilted, with a hook in the proximal part of the tiltable plate that serves to anchor the lungs at the carina, keeping them suspended when in an orthostatic position. The length of the hook can be adjusted according to the size of the graft, offering flexibility for different organ dimensions.
The study used an adult pig model, with a heart-lung block harvested and subjected to 4 hours of static cold preservation, simulating a donation after cardiac death (DCD) scenario. The EVLP procedure was conducted for 4 hours, with progressive positioning towards the orthostatic position during the first hour of perfusion.
The EVLP protocol used in this study was based on the Toronto protocol, with gradual warming and progressive increase in vascular flow. The target perfusion flow was gradually reached in one hour. At 10 minutes from the start, the flow was increased to 20% of the calculated theoretical flow and the temperature set to 30°C. The flow was then progressively increased to 30%, 50%, 80%, and finally 100% of the target, respectively every 10 minutes, and ventilation was initiated when the temperature reached 32°C.
Compared to standard EVLP techniques that maintain the lungs in a supine position, this new orthostatic approach aims to overcome problems of non-homogeneous perfusion. Standard techniques can lead to hyperperfusion of the lower dependent regions and hypoperfusion of the non-dependent regions, potentially causing an asymmetric distribution of ventilation-perfusion. The orthostatic approach seeks to improve this distribution, reducing capillary shear stress and pulmonary edema accumulation.
This technique could have significant implications for the use of lungs from DCD donors. Lungs from these donors are often considered marginal and can particularly benefit from advanced preservation techniques. Orthostatic EVLP aims to improve the quality of these organs, increasing the number of lungs suitable for transplantation from this donor source.
The study results highlighted several positive aspects. A remarkable stability of gas exchange was observed, with the ΔPaO2 (difference between pre and post PaO2) remaining above 300 mmHg for 4 hours, reaching an average value of 366 ± 30 mmHg. This data is particularly significant as it demonstrates the system’s ability to maintain optimal lung function for an extended period.
Analysis of parameters during the inclination phases showed significant improvement. Static compliance progressively increased from 75 to 84 cm H2O/ml. The ΔPaO2/FiO2 recorded a notable increase in the first orthostatic phase (from 297 to 389 mmHg), remaining elevated in subsequent phases. These data support the effectiveness of the orthostatic approach in improving lung function during EVLP.
In parallel, the study revealed a marked stability of respiratory mechanics. The peak and plateau airway pressures, as well as dynamic and static compliance, remained constant throughout the procedure. These parameters are indicative of good preservation of lung structure and functionality during the orthostatic EVLP process.
Macroscopic evaluation provided further evidence of this technique’s effectiveness. The lungs maintained a stable appearance throughout the procedure, showing no evident signs of lobar congestion or atelectasis. Of particular interest was the observation of improved expansion of the dorsal areas of the graft, simulating the physiological movement of the lungs in a standing subject.
Histological analysis further confirmated the macroscopic and physiological results. Microscopic examination of lung tissues revealed no edema or congestion in the analyzed samples. Granulocyte infiltration was sporadic in the pulmonary interstitium and absent in the alveoli, indicating a minimal inflammatory response. Moreover, the absence of hemorrhages or micro-thrombosis suggests that the technique did not cause significant vascular damage.
The evaluation methods used in this study included not only physiological and histological parameters but also a detailed macroscopic assessment of color changes and lung expansion during perfusion, providing a comprehensive view of organ functionality and quality.
These results, considered together, suggest that the orthostatic approach during EVLP is feasible and potentially advantageous for preserving lungs intended for transplantation. The stability of physiological parameters, combined with the absence of significant histological damage, indicates that this innovative technique could improve the quality of organs available for transplantation.
The introduction of the adjustable PerLungs® dome represents a significant step forward in the field of EVLP. By addressing the issue of graft position during the procedure, this technology could improve the effectiveness of ex vivo perfusion, contributing to increasing the availability of organs suitable for transplantation.
This study opens new perspectives in the field of organ preservation for lung transplantation. The orthostatic approach during EVLP, made possible by the adjustable PerLungs® dome, could represent a significant advancement in the management of donated lungs. By improving the quality of organs available for transplantation, this technology could contribute to increasing the number of feasible lung transplants and improving patient outcomes.
The potential future applications of this technology are vast. In addition to improving organ preservation, it could allow for a more accurate assessment of marginal lungs, potentially expanding the donor pool. Furthermore, in combination with other methods, it could pave the way for new ex vivo treatment strategies to recondition organs initially unsuitable for transplantation.