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Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1825-1833

Effects of Inter-alpha -inhibitor in Experimental Endotoxic Shock and Disseminated Intravascular Coagulation

MERCÉ JOURDAIN, ODILE CARRETTE, ANTOINE TOURNOYS, FRANÇOIS FOURRIER, CHARLOTTE MIZON, JACQUES MANGALABOYI, JENNY GOUDEMAND, JACQUES MIZON, and CLAUDE CHOPIN

Equipe recommandée 150. DRED, Equipe associée 1052, DRED, Equipe d'accueil 1044. DRED, Université de Lille II, and Service de Réanimation Polyvalente, Hôpital Roger Salengro, Lille, France

We investigated the effects of human inter-alpha -inhibitor (Ialpha I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) Ialpha I group receiving 30 mg/kg Ialpha I over 30 min, (3) LPS group receiving 5 µg · kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + Ialpha I group receiving 30 min after endotoxin 30 mg/kg/30 min Ialpha 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 Ialpha I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the Ialpha I group, plasma Ialpha I levels reached 447 ± 23 mg/L just after injection and 287 ± 39 mg/L at 300 min. Ialpha I half-life was 7.3 ± 1.9 h. In the LPS + Ialpha I group, Ialpha I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of Ialpha 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, Ialpha I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.




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