TY - JOUR
T1 - Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits
AU - Roback, Mark G.
AU - Stack, Anne M.
AU - Thompson, Claudette
AU - Brugnara, Carlo
AU - Schwarz, H. Peter
AU - Saladino, Richard A.
PY - 1998/2
Y1 - 1998/2
N2 - 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 μg/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 μg/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 μg/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 μg/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 ≤ .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.
AB - 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 μg/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 μg/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 μg/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 μg/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 ≤ .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.
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U2 - 10.1097/00024382-199802000-00011
DO - 10.1097/00024382-199802000-00011
M3 - Article
C2 - 9488260
AN - SCOPUS:0031989122
SN - 1073-2322
VL - 9
SP - 138
EP - 142
JO - Shock
JF - Shock
IS - 2
ER -