What does this research mean for the field?

Negative-pressure ventilation reduces regional strain, anisotropic distortion, and hysteresis compared to positive-pressure ventilation in ventilator-induced lung injury, suggesting it may mitigate progressive mechanical damage. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

This research aims to explore the mechanical differences in injury caused by positive-pressure versus negative-pressure ventilation in both healthy and surfactant-depleted lungs.

May 17, 2026Open Access

Injury Mechanics in Surfactant-Depleted and Healthy Rat Lungs: A Multi-scale Consideration of Artificial and Physiological Ventilation

Key Points

This research aims to explore the mechanical differences in injury caused by positive-pressure versus negative-pressure ventilation in both healthy and surfactant-depleted lungs.
Examined three groups of rat lungs: uninjured controls, VILI-Only (high tidal volume with zero positive end-expiratory pressure), and surfactant-depleted VILI lungs.
Utilized a custom-designed electromechanical apparatus and digital image correlation for assessment at organ and tissue levels.
Confirmed microstructural damage through confocal microscopy.
VILI-Only lungs showed a 6% increase in regional strain, with similar static compliance compared to controls.
Surfactant-depleted VILI lungs exhibited greater strain and compliance increases compared to both controls and VILI-Only.
NPV reduced mean strain by 9% and hysteresis by 25% in VILI-Only lungs compared to PPV, while promoting isotropic deformation.

Abstract

Abstract Purpose Ventilator-induced lung injury (VILI) causes regional pulmonary damage and remains a medical challenge. While the clinical standard, positive-pressure ventilation (PPV), has been contrasted with physiological negative-pressure ventilation (NPV), the discrepancy between ventilation modes on VILI remains unstudied. Methods To elucidate possible VILI mechanics from alveolar overdistension and distortion, three groups of rat lungs were examined: uninjured controls, lungs subjected to high tidal volume with zero positive end-expiratory pressure to induce VILI, denoted VILI-Only, and surfactant-depleted VILI lungs. PPV and NPV mechanics were continuously assessed at the organ- and tissue-level with a custom-designed electromechanical apparatus paired to digital image correlation, where confocal microscopy confirmed microstructural damage. Results Compared to controls, VILI-Only increased regional strain by 6% while static compliance remained similar. Surfactant-depleted VILI lungs exhibited greater strain and compliance increases, and both injury groups showed elevated strain anisotropy. In VILI-Only lungs, NPV compared to PPV, reduced mean strain (9%), anisotropic distortion, and hysteresis (25%) relative to PPV, while promoting more isotropic deformation in right lung lobes. In surfactant-depleted VILI lungs, NPV reduced inflation compliance relative to PPV, but did not lessen regional strain. Notably, NPV revealed greater pressure relaxation in VILI-Only, a non-observed effect with PPV. Conclusion Altogether, VILI-Only and surfactant-depleted VILI produced elevated strain and anisotropic deformation, indicating damaging regional inflation. NPV revealed more prominent alterations in lung behavior, including pressure relaxation and strain significances, indicating improved sensitivity to early dysfunction. In VILI-Only lungs, NPV also reduced strain and anisotropy, suggesting physiological breathing may mitigate progressive VILI-induced mechanical damage.

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