Protein C preserves microcirculation in a model of neonatal septic shock.
OBJECTIVE
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.


METHODS
Endotoxic shock was triggered by intravenous application of Escherichia coli lipopolysaccarides in newborn piglets. Thereafter, five animals received a continuous infusion of 24 microg/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.


CONCLUSIONS
Recombinant activated protein C protects macro- and microcirculation from endotoxic shock.
Department of Pediatrics, Hospital of the J W Goethe University, Frankfurt, Germany. doris.fischer@kgu.de
Doris
D
Fischer
Marcel F
MF
Nold
Claudia A
CA
Nold-Petry
Antonio
A
Furlan
Alex
A
Veldman
D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D007422:Intestines / Q000098:blood supply*; D008070:Lipopolysaccharides; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video; D011486:Protein C / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013997:Time Factors
D008070:Lipopolysaccharides; D011486:Protein C; D011994:Recombinant Proteins; C440499:lipopolysaccharide, Escherichia coli O111 B4