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Computational physiological modeling for lung-specific ventilation and perfusion management in <i>ex vivo</i> lung perfusion.


ABSTRACT:

Introduction

Ex vivo lung perfusion (EVLP) relies on standardized ventilation and perfusion protocols to evaluate and preserve donor lungs before transplantation. Yet, these protocols overlook graft-specific physiology, leading to variable dead-space ventilation, intrapulmonary shunting, and increased lung injury.

Methods

We developed and validated a computational physiological model (CPM) of lungs on EVLP. The CPM integrates established principles of lung mechanics, gas exchange, and perfusion with clinical input data. It provides mechanistic insight into ex vivo lung physiology and quantifies intrinsic properties such as alveolar dead space and intrapulmonary shunting. Model validation combined in silico experiments to verify physiological coherence with calibration against clinical EVLP data to evaluate predictive performance.

Results

Simulation results closely aligned with clinical measurements of left atrial partial oxygen pressure (root mean squared error (RMSE) of 6.4 mmHg). Sensitivity analysis and uncertainty quantification further elucidated key determinants of oxygen and carbon dioxide dynamics, including the inspired oxygen fraction, intrapulmonary shunt, dead space, and perfusate flow.

Discussion

This CPM enhances understanding of ex vivo lung physiology, which may lead to less injurious EVLP management and support safe, extended-duration EVLP.

SUBMITTER: Imholz D 

PROVIDER: S-EPMC12909158 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

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Publications

Computational physiological modeling for lung-specific ventilation and perfusion management in &lt;i&gt;ex vivo&lt;/i&gt; lung perfusion.

Imholz Daan D   Braithwaite Sue A SA   Blankman Paul P   Oppersma Eline E   de Jongh Frans H C FHC   de Heer Linda M LM   Luijk Bart B   Buhre Wolfgang F F A WFFA   Donker Dirk W DW   van Loon Lex M LM  

Frontiers in physiology 20260203


<h4>Introduction</h4><i>Ex vivo</i> lung perfusion (EVLP) relies on standardized ventilation and perfusion protocols to evaluate and preserve donor lungs before transplantation. Yet, these protocols overlook graft-specific physiology, leading to variable dead-space ventilation, intrapulmonary shunting, and increased lung injury.<h4>Methods</h4>We developed and validated a computational physiological model (CPM) of lungs on EVLP. The CPM integrates established principles of lung mechanics, gas ex  ...[more]

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