Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin.
OBJECTIVE
To assess the effect of a combined antithrombin III and C1-esterase inhibitor treatment on intravascular organ fibrin deposition and cardiorespiratory changes following intravenous Escherichia coli endotoxin (lipopolysaccharide [LPS] 80 microg/kg i.v.) exposure.


METHODS
Prospective, randomized trial.


METHODS
Research laboratory of a university medical center.


METHODS
Anesthetized, instrumented and mechanically ventilated rabbits ([Chbb:CH); n = 40).


METHODS
Endotoxin was given to 30 animals. Ten animals received no inhibitor (endotoxin control group). The other animals were either treated by high-dose (300 units/kg; n = 10) or low-dose (100 units/kg; n = 10) combined antithrombin III and C1-esterase inhibitor administration. Ten rabbits (time control group) were given placebo (sodium chloride 0.9%). Cardiorespiratory variables were assessed at baseline, 120 mins, and 240 mins after endotoxin or placebo administration. Four hours after endotoxin injection, liver, lung, and kidney tissue samples were examined for intravascular fibrin deposition by light microscopy.


RESULTS
Inhibitor treatment significantly decreased clot formation in lungs and livers without, however, demonstrating a clear dose-dependent effect. Combined antithrombin III/C1-esterase treatment attenuated the decrease of mean arterial pressure and cardiac output observed following endotoxin injection. Blood pressure improvement was significantly dependent on dosage administered.


CONCLUSIONS
Combination of antithrombin III and C1-esterase inhibitor treatment during early endotoxin shock decreased organ fibrin deposition and improved cardiovascular stability.
Giebler
R
R
Abteilung für Anästhesiologie und Intensivmedizin, Klinikum der Universität-GH Essen, Germany.
Schmidt
U
U
Koch
S
S
Peters
J
J
Scherer
R
R
D000818:Animals; D000990:Antithrombin III / Q000008:administration & dosage / Q000627:therapeutic use*; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004731:Endotoxins / Q000009:adverse effects; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy*; D005337:Fibrin / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
D000991:Antithrombins; D003174:Complement C1 Inactivator Proteins; D004338:Drug Combinations; D004731:Endotoxins; D000990:Antithrombin III; D005337:Fibrin