Panel A depicts the evolution of venous admixture (Qs/Qt) in anesthetized beagles subject to high tidal volume mechanical ventilation after intrabronchial administration of bacterial LPS (2–4 mg/kg, black squares, n=9) or intrabronchial LPS plus intravenous S1P one hour later (85 μg/kg, gray circles, n=9). Beagles receiving S1P demonstrated significant reductions in shunt formation beginning 5.5 hours after LPS instillation compared to those receiving LPS alone. Panel B depicts the time-dependent accumulation of protein in the BAL fluid of anesthetized beagles subject to high tidal volume mechanical ventilation after intrabronchial administration of bacterial LPS (2–4 mg/kg, black bars, n=9) or intrabronchial LPS plus intravenous S1P one hour later (85 μg/kg, gray bars, n=9). Mean ± SEM, *p≤0.05 LPS compared to LPS+S1P, † p≤0.05 compared to 90 min, ‡p<0.05 compared to baseline, ††p<0.05 compared to baseline, 3, and 5 hr. Qs/Qt is significantly elevated relative to baseline for all t ≥30 min.