# Ventilation–perfusion effects of negative-pressure ventilation: insights from an experimental rat model

## TL;DR

This study compares negative-pressure ventilation to traditional positive-pressure ventilation in rats, finding that it improves gas exchange and ventilation-perfusion matching.

## Contribution

The study provides new experimental evidence on how negative-pressure ventilation affects ventilation-perfusion matching in healthy lungs.

## Key findings

- NPV improved gas exchange with higher PaO2 and lower PaCO2 compared to PPV.
- NPV reduced ventilation-perfusion inequalities and dead space ventilation compared to PPV.
- Excessive negative end-expiratory pressure during NPV increased intrapulmonary shunting.

## Abstract

Mechanical ventilation typically utilizes positive-pressure ventilation (PPV), which fundamentally differs from physiological pressure conditions. In contrast, negative-pressure ventilation (NPV) more closely mimics physiological pressure conditions; however, its impact on ventilation–perfusion matching remains unclear. Therefore, we compared PPV and NPV in terms of their effects on ventilation–perfusion matching and determined the consequences of increasing end-expiratory pressure (EEP).

Anesthetized rats (n = 9) were ventilated using PPV at a positive EEP of 0, 3, 6, and 9 cmH2O. NPV was initiated by placing the rats in a sealed chamber and generating cyclic negative-pressure changes around the body while maintaining identical EEP and tidal volumes. At each EEP level, the arterial partial pressures of oxygen (PaO2) and CO2 (PaCO2) were measured from blood samples. Phase 2 (S2V) and 3 slopes (S3V), Fowler’s anatomical dead space fraction (VDF), and physiological dead space fractions according to Bohr (VDB) and Enghoff (VDE) were determined by volumetric capnography.

Higher PaO2 and lower PaCO2 were observed during NPV compared with PPV. The lower S2V and S3V values were associated with reduced VDF and VDB during NPV, whereas VDE including alveolar compartments with intrapulmonary shunt was higher. Elevating positive EEP during PPV increased S2V, S3V, and VDB, whereas the same lung expansion with NPV had a smaller effect.

The results indicate that compared with PPV, NPV enhances gas exchange and ventilation–perfusion matching in healthy lungs. Although NPV causes fewer ventilation–perfusion inequalities and reduced dead space ventilation, its efficacy may be limited by increased intrapulmonary shunting during excessive negative end-expiratory pressure levels. These results provide mechanistic support for the physiological benefits of subatmospheric ventilation and may provide a basis for further studies on the refinement of noninvasive and lung-protective ventilation strategies in clinical settings with impaired ventilation–perfusion matching, such as acute respiratory failure, postoperative care, and ventilator weaning.