Abstract Rationale Septic shock causes profound pulmonary blood flow (PBF) dysregulation, characterized by systemic vasoplegia, impaired hypoxic pulmonary vasoconstriction, perfusion maldistribution, and right ventricular strain. Current animal models primarily focus on ventilator-induced lung injury and often fail to replicate the early pulmonary vascular failure and perfusion abnormalities seen in human sepsis. Objectives To develop a swine model of septic shock that quantitatively reproduces pulmonary vascular dysfunction and ventilation-perfusion (V/Q) uncoupling by integrating continuous mPAP monitoring and regional perfusion mapping with electrical impedance tomography (EIT). Methods Swine received intravenous lipopolysaccharide (LPS) infusion combined with injurious mechanical ventilation. Advanced hemodynamic monitoring included continuous measurement via pulmonary artery and arterial catheters. Regional PBF distribution was assessed using hypertonic saline enhanced EIT at baseline and 7 hours, comparing dependent vs. nondependent lung zones. Results Static lung compliance declined from 33±10 to 19±6 mL/cmH2O within 1 hour, and remained reduced (16-22 mL/cmH2O) through 7 hours. Mean pulmonary artery pressure (mPAP) increased from 19 ± 3 to 32 ± 5 mmHg (+68%), despite systemic vasodilation, indicating rising right ventricular afterload and reduced pulmonary vascular compliance. EIT demonstrated perfusion redistribution away from dependent lung regions (52% to 28%), with concurrent increases in low V/Q and true shunt (12% to 31%). These changes occurred before significant hypoxemia, or overt ventilation-induced injury suggesting ventilation-perfusion matching dysregulation as primary driver of lung injury. Conclusions This large-animal model shows that LPS triggers early pulmonary injury, evidenced by rising mPAP that mirrors the hemodynamic profile of septic shock. Concurrently, static lung compliance declined rapidly, indicating early loss of lung elasticity despite preserved oxygenation. EIT further confirmed perfusion maldistribution and impaired hypoxic pulmonary vasoconstriction, resulting in V/Q uncoupling and redistribution of blood flow toward non-dependent and poorly ventilated lung regions. Together, these data suggest that early phase perfusion-ventilaiton uncoupling might be the first insult in sepsis-associated lung injury, precipitating gas exchange impairment and progression toward lung failure. By capturing this early uncoupling phase, the model provides a translational platform for mechanistic studies and for testing perfusion-targeted and ventilation protective therapies before structural lung injury becomes established. This abstract is funded by: None
Othman et al. (Fri,) studied this question.