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

Abstract Background 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). Methods Anesthetized rats (n = 9) were ventilated using PPV at a positive EEP of 0, 3, 6, and 9 cmH 2 O. 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 (PaO 2 ) and CO 2 (PaCO 2 ) 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. Results Higher PaO 2 and lower PaCO 2 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. Conclusions 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.