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 mod el of meningococcal endotoxin-induced shock, we performed a prospectiv e, blinded, placebo-controlled animal trial, Forty New Zealand White r abbits were challenged with intravenous meningococcal endotoxin (lipoo ligosaccharide) 100 mu g/kg. Ten minutes before endotoxin challenge, a nimals were administered either activated protein C 1600 mu g/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus, After e ndotoxin challenge, activated protein C treated animals were administe red a continuous infusion of activated protein C 160 mu g/kg/h and sal ine-treated animals were administered an equal volume infusion of sali ne. Both activated protein C treated and saline control animals demons trated evidence of shock after endotoxin challenge: mean arterial pres sure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline. In activated pr otein C treated animals, mean plasma activated protein C activity was 5.69 mu g/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C a ctivity was not detected in controls. Mean prothrombin and activated p artial thromboplastin times were significantly (p less than or equal t o. 01) prolonged compared with saline-treated controls. Other hematolo gic and chemical measurements did not differ between groups. Fifteen o f 20 (75%) animals treated with activated protein C concentrate surviv ed 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 surv ival, which corroborates the findings of early clinical studies in whi ch replacement of protein C improved outcome.