LOWERING PULMONARY VASCULAR RESISTANCE IMPROVES HEMODYNAMICS AND FLUID RESPONSIVENESS IN A PORCINE MODEL OF LPS-INDUCED SHOCK.

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 administering 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 LPS-induced endotoxic shock were randomized into four groups in two parts (n = 6 per group): part 1 (control group and treprostinil treatment group) and part 2 (fluid resuscitation group 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, right ventricular stroke volume, 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 cardiac output, right ventricular stroke volume, right ventricular ejection fraction, 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 PVR could be a potential adjunctive strategy for managing shock in critically ill patients.