Human ex-vivo lung mechanics differ under positive- and negative-pressure ventilation

Clinical and mechanical studies reveal key differences between positive- and negative-pressure ventilation, yet their equivalencyPlease check if the authors and their affiliation are presented and indicated correctly. remains a topic of debate. This debate is perpetuated by contradictory reports from a variety of small- and large-scale animal models. While the usage of animal models has been transformative with incomparable advantages for advancing research efforts, they partially limit the translatability of findings to clinical settings and the accurate assessment of ventilation mode dependencies. For the first time, we inflate ten ex-vivo donated cadaveric human lungs with both positive- and negative-pressure to evaluate mechanistic differences between these ventilation modes and subsequently analyzed the obtained pressure-volume curves using our custom electromechanical ventilator. We report end-inspiratory metrics with disparate end-expiratory and plateau pressures, dynamic compliances, resistance, and viscoelastic metrics between ventilation modes. These rare human lung findings are partly consistent with past animal studies, which reported matched peak pressure-volume behaviors with differing inflation compliances between positive- and negative-pressure ventilation. Differing deflation compliance and end-expiration pressures have not been demonstrated under animal models, highlighting the need for human organ testing. Results suggest distinct recruitment patterns between ventilation modes, providing mechanical insights linked to reports of better oxygenation in negative-pressure ventilation and potential contributors to ventilator-induced lung injury in positive-pressure ventilation.