Protein C preserves microcirculation in a model of neonatal septic shock

Abstract

Objectives

Sepsis remains a disease with a high mortality in neonates. Microcirculatory impairment plays a pivotal role in the development of multiorgan failure in septic newborns. The hemodynamic effects of recombinant activated protein C (rhAPC) were tested in an animal model of neonatal septic shock focusing on intestinal microcirculation.

Materials and methods

Endotoxic shock was triggered by intravenous application of Escherichia coli lipopolysaccarides in newborn piglets. Thereafter, five animals received a continuous infusion of 24 μg/kg/h rhAPC, and five received vehicle for control. Over the course of three hours, intestinal microcirculation was assessed by intravital microscopy every 30 min. Macrocirculation and blood counts were monitored simultaneously.

Results

After a short hypotensive period in all animals, the arterial blood pressure returned to baseline in the rhAPC-treated piglets, whereas the hypotension became increasingly severe in the controls. By 90 min, mean blood pressure in the controls was significantly lower than in the treatment group. Similar observations were made regaring microcirculation. After an early impairment in all study animals, functional capillary density and intestinal microcirculatory red blood cell velocity and red blood cell flow recovered in the rhAPC group, but deteriorated further in the control piglets.

Conclusion

Recombinant activated protein C protects macro- and microcirculation from endotoxic shock.

Keywords:

• protein C
• neonatal septic shock
• microcirculation
• intravital microscopy

Acknowledgments

We would like to thank Prof Philip Berger and Elizabeth Skuza for their help in data analysis and review of the manuscript. Dr Alex Veldman is a member of the Baxter Advisory Board and as such receives an honorarium. All other authors declare that there are no financial or other conflicts of interest. This study was not supported by any industrial grant.