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 mi n, (3) LPS group receiving 5 mu g.kg/min Escherichia coli endotoxin ov er 30 min, and (4) LPS + I alpha I group receiving 30 min after endoto xin 30 mg/kg/30 min I alpha I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-a ntithrombin complexes, antithrombin III activity, plasminogen activato r 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 LPS + I alpha I group, I alpha I plasma levels decreased more rapidly , reaching 260 mg/L at 300 min. Compared with the LPS group, administr ation of I alpha I normalized the mean arterial pressure and cardiac i ndex, 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 plasminoge n activator inhibitor type 1 levels were observed. There was no signif icant difference in plasma tumor necrosis factor-alpha levels. We conc luded that in this hypodynamic model of endotoxin shock, I alpha I adm inistration resulted in a marked improvement in the hemodynamic, oxyge nation, and coagulation parameters.