Effects of inter-alpha-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation.
We investigated the effects of human inter-alpha-inhibitor (I alpha I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) I alpha I group receiving 30 mg/kg I alpha I over 30 min, (3) LPS group receiving 5 micrograms.kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + I alpha I group receiving 30 min after endotoxin 30 mg/kg/30 min I alpha I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-antithrombin complexes, antithrombin III activity, plasminogen activator tissue type, plasminogen activator inhibitor type 1, von Willebrand factor, tumor necrosis factor-alpha, and I alpha I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the I alpha I group, plasma I alpha I levels reached 447 +/- 23 mg/L just after injection and 287 +/- 39 mg/L at 300 min. I alpha I half-life was 7.3 +/- 1.9 h. In the IPS + I alpha I group, I alpha I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of I alpha I normalized the mean arterial pressure and cardiac index, improved the LPS-induced pulmonary hypertension, and resulted in the blunted increase in blood lactate and oxygen extraction ratio. A significant decrease in thrombin-antithrombin complexes and plasminogen activator inhibitor type 1 levels were observed. There was no significant difference in plasma tumor necrosis factor-alpha levels. We concluded that in this hypodynamic model of endotoxin shock, I alpha I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.
Jourdain
M
M
Equipe recommandée 150. DRED, Université de Lille II, France.
Carrette
O
O
Tournoys
A
A
Fourrier
F
F
Mizon
C
C
Mangalaboyi
J
J
Goudemand
J
J
Mizon
J
J
Chopin
C
C
D000510:Alpha-Globulins / Q000627:therapeutic use*; D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001772:Blood Cell Count; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D004926:Escherichia coli; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006439:Hemodynamics; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D010100:Oxygen / Q000097:blood; D010447:Peptide Hydrolases / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011517:Prothrombin Time; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D012772:Shock, Septic / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D000510:Alpha-Globulins; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; D019344:Lactic Acid; C011877:inter-alpha-inhibitor; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D010100:Oxygen