TY - JOUR
TI - Administration of human protein C improves survival in an experimental model of sepsis
AU - Messaris, E.
AU - Betrosian, A.P.
AU - Memos, N.
AU - Chatzigianni, E.
AU - Boutsikou, M.
AU - Economou, V.
AU - Dontas, I.
AU - Theodossiades, G.
AU - Konstadoulakis, M.M.
AU - Douzinas, E.E.
JO - Pediatric Critical Care Medicine
PY - 2010
VL - 38
TODO - 1
SP - 209-216
PB - Lippincott Williams and Wilkins
SN - 1529-7535
TODO - 10.1097/CCM.0b013e3181b4a972
TODO - alpha 1 antitrypsin;  interleukin 6;  placebo;  protein C;  tumor necrosis factor;  cytokine;  protein C, animal experiment;  animal model;  animal tissue;  apoptosis;  article;  brain tissue;  cecum;  colon;  controlled study;  cytokine production;  heart;  kidney parenchyma;  ligation;  lung parenchyma;  male;  nonhuman;  organ injury;  priority journal;  protein blood level;  puncture;  rat;  sepsis;  stomach;  survival;  animal;  blood;  cecum;  chi square distribution;  comparative study;  disease model;  enzyme linked immunosorbent assay;  flow cytometry;  human;  immunohistochemistry;  Kaplan Meier method;  mortality;  nick end labeling;  nonparametric test;  pathology;  probability;  randomization;  survival rate;  Wistar rat, Animals;  Cecum;  Chi-Square Distribution;  Cytokines;  Disease Models, Animal;  Enzyme-Linked Immunosorbent Assay;  Flow Cytometry;  Humans;  Immunohistochemistry;  In Situ Nick-End Labeling;  Kaplan-Meiers Estimate;  Ligation;  Male;  Probability;  Protein C;  Random Allocation;  Rats;  Rats, Wistar;  Sepsis;  Statistics, Nonparametric;  Survival Rate
TODO - OBJECTIVE: Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. DESIGN: Animal study. SETTING: University laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. MEASUREMENTS AND MAIN RESULTS: PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p =.001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p =.009, p =.004, and p =.008, respectively) and to late septic CLP and normal rats (p =.005 and p =.007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p =.008 and p =.016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p =.001). Apoptosis was reduced in brain (10% vs. 77.8%, p <.001), stomach (66.7% vs. 100%, p <.002) and intestine (33.3% vs. 85.2%, p <.001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p =.033). CONCLUSIONS: Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs. Copyright © 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
ER -