Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits.
To evaluate the effects of activated protein C therapy in a rabbit model of meningococcal endotoxin-induced shock, we performed a prospective, blinded, placebo-controlled animal trial. Forty New Zealand White rabbits were challenged with intravenous meningococcal endotoxin (lipooligosaccharide) 100 microg/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 microg/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus. After endotoxin challenge, activated protein C treated animals were administered a continuous infusion of activated protein C 160 microg/kg/h and saline-treated animals were administered an equal volume infusion of saline. Both activated protein C treated and saline control animals demonstrated evidence of shock after endotoxin challenge; mean arterial pressure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline. In activated protein C treated animals, mean plasma activated protein C activity was 5.69 microg/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C activity was not detected in controls. Mean prothrombin and activated partial thromboplastin times were significantly (p < or = .01) prolonged compared with saline-treated controls. Other hematologic and chemical measurements did not differ between groups. Fifteen of 20 (75%) animals treated with activated protein C concentrate survived to 24 h, while 9 of 20 (45%) control animals survived to 24 h (p = .05). Those animals treated with activated protein C had improved survival, which corroborates the findings of early clinical studies in which replacement of protein C improved outcome.
Roback
M G
MG
Department of Medicine, Children's Hospital, Denver, Colorado 80218, USA.
Stack
A M
AM
Thompson
C
C
Brugnara
C
C
Schwarz
H P
HP
Saladino
R A
RA
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D005340:Fibrinogen / Q000032:analysis / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D007958:Leukocyte Count / Q000187:drug effects; D008589:Meningococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010976:Platelet Count / Q000187:drug effects; D011486:Protein C / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D011817:Rabbits; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013534:Survival; D013927:Thrombosis / Q000517:prevention & control
D004731:Endotoxins; D006454:Hemoglobins; D011486:Protein C; D011516:Prothrombin; D005340:Fibrinogen