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Updated: May 24, 2026

Normothermic Negative Pressure Ventilation Ex Situ Lung Perfusion: Evaluation of Lung Function and Metabolism
Published on: February 14, 2022
Relative effects of negative versus positive pressure ventilation depend on applied conditions
Doreen Engelberts1, Atul Malhotra, James P Butler
1Program in Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Canada.
Purpose:
Comparisons of negative versus positive pressure ventilation have imperfectly matched the pressure-time profile or the lung volume history, or have incompletely applied in vivo negative pressure to include the complete thoracic wall and abdomen.
Hypothesis:
Negative pressure exerts the same pattern of lung distension as positive pressure when the pressure-time and volume history profiles are identical and the application of negative pressure is over the whole lung.
Methods:
(1) In isolated (ex vivo) and (2) intact (in vivo) mouse lungs (n = 4/group) (sealed chamber enclosing either the whole lung or whole mouse except for external airway opening), identical and inverse-tidal, square-wave pressure-time profiles were obtained with positive and negative pressure ventilation. (3) Following an identical volume history, surfactant-depleted rabbits (n = 7) were randomly assigned to sustained, static equivalent positive versus negative pressures. (4) Surfactant-depleted anesthetized rabbits (n = 10) with identical volume histories were randomized to positive versus negative ventilation with identical pressure-time characteristics.
Results:
Matched positive and negative pressure time profiles in ex vivo and in vivo mice resulted in identical tidal volumes. Identical (negative vs. positive) sustained static pressures resulted in similar PaO(2) and end expiratory lung volumes. Positive and negative ventilation with identical volume histories and pressure time characteristics showed no difference in oxygenation or lung volumes. Historical comparisons suggested better oxygenation with negative pressure when the volume history was not identical.
Conclusions:
These data do not support major biological differences between negative and positive pressure ventilation when waveforms and lung volume history are matched.
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