Effects of inter-α-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation

• Published in: American journal of respiratory and critical care medicine 1997-12, Vol.156 (6), p.1825-1833
• Main Authors: JOURDAIN, M, CARRETTE, O, TOURNOYS, A, FOURRIER, F, MIZON, C, MANGALABOYI, J, GOUDEMAND, J, MIZON, J, CHOPIN, C
• Format: Article
• Language: English
• Subjects: Alpha-Globulins - therapeutic use; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antithrombin III - analysis; Biological and medical sciences; Blood Cell Count; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - complications; Disseminated Intravascular Coagulation - physiopathology; Disseminated Intravascular Coagulation - therapy; Emergency and intensive care: infection, septic shock; Escherichia coli; Female; Fibrinogen - analysis; Hemodynamics; Intensive care medicine; Lactic Acid - blood; Lipopolysaccharides; Medical sciences; Oxygen - blood; Peptide Hydrolases - analysis; Plasminogen Activator Inhibitor 1 - analysis; Prothrombin Time; Serine Proteinase Inhibitors - therapeutic use; Shock, Septic - blood; Shock, Septic - complications; Shock, Septic - physiopathology; Shock, Septic - therapy; Swine; Tissue Plasminogen Activator - analysis; Tumor Necrosis Factor-alpha - analysis; von Willebrand Factor - analysis
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.156.6.9611100

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.