Lowering pulmonary vascular resistance improves hemodynamics and fluid responsiveness in a porcine model of LPS-induced shock

Abstract Background Septic pulmonary hypertension disrupts the homeostasis between the left- and right-sided heart, and is associated with poor prognosis. This study assessed whether lowering the pulmonary vascular resistance (PVR) by administrating the prostacyclin analog treprostinil would improve hemodynamics, short - term survival, and fluid resuscitation in endotoxic shock. Methods A preclinical randomized controlled study was conducted. Bama miniature pigs (n = 24; 12 male and 12 female) with lipopolysaccharide (LPS)-induced endotoxic shock were randomized into: four groups in 2 parts (n = 6 per group): part 1 (control group and treprostinil treatment group) and part 2 (fluid resuscitation group and and treprostinil treatment + fluid resuscitation group). The primary outcome measures were cardiac performance and short - term survival, and the secondary outcome measures were mean urine volume, fluid balance volume, and norepinephrine consumption. Results Compared with the control group, the treprostinil treatment group showed significantly reduced PVR, increased cardiac output (CO), right ventricular stroke volume (RVSV), right ventricular ejection fraction (RVEF), short-term survival, and mean urine volume. Compared with the fluid resuscitation group, the treprostinil treatment + fluid resuscitation group exhibited notably reduced PVR, increased CO, RVSV, RVEF, and decreased fluid balance volume, with no statistically significant difference in norepinephrine consumption. Conclusion The high-resistance pulmonary circulation in endotoxic shock acted as an "obstruction" impeding the blood flow from the right to the left side of the heart. Weakening this "obstruction" improved cardiac performance and fluid responsiveness in an experimental endotoxic shock model, suggesting that targeting pulmonary vascular resistance could be a potential adjunctive strategy for managing shock in critically ill patients.