Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model

Area of Science:

• Organ transplantation
• Ex vivo lung perfusion (EVLP)
• Cellular metabolism

Background:

• Normothermic ex vivo lung perfusion (EVLP) expands donor lung availability by improving marginal lungs.
• EVLP perfusate can accumulate harmful byproducts affecting organ and cell health.
• These byproducts may negatively impact lung transplantation outcomes.

Purpose of the Study:

• To investigate the physiological, metabolic, and genomic responses of lungs during EVLP.
• To evaluate the impact of perfusate modification (fluid replacement, dialysis) on lung physiology and gene expression.
• To assess the safety and efficacy of EVLP management strategies.

Main Methods:

• A 6-hour EVLP procedure was performed on pig lungs.
• Four experimental conditions were tested: no modification, partial fluid replacement, adult dialysis, and pediatric dialysis.
• Physiological parameters, metabolic profiles, and genome-wide gene expression were analyzed.

Main Results:

• Both adult and pediatric dialysis stabilized electrolytes and metabolites while maintaining gas exchange.
• Pediatric dialysis increased IL-10 and IL-6 levels in the perfusate.
• Despite perfusate changes, all EVLP conditions preserved lung gene expression profiles, promoting cell survival, proliferation, and inflammatory responses.

Conclusions:

• Perfusate management via replacement or dialysis does not significantly affect ex vivo lung function or gene expression.
• Accumulated dialyzable cell products during EVLP do not substantially alter lung cell responses.
• These findings support the clinical use of EVLP with current management strategies for lung recovery.