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

Abstract

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.

Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock

“…180 min and T ? 300 min, respectively, and decreased steadily from 45 (20) to 18 (13) ml/min/m 2 in controls (p = 0.030). There were no significant differences between groups for any other hemodynamics variables, except for systemic vascular resistance (SVR) (p = 0.017).…”

“…An esophageal temperature probe allowed continuous monitoring of body temperature, which was kept at 38°C by use of heat lamps suspended above the operating table. Heart rate and systemic and pulmonary arterial pressures were continuously monitored (7758B cardiac monitor; Hewlett Packard, Palo Alto, CA, USA) as well as cardiac output and SvO 2 (Vigilance monitor; Baxter Edwards, Irvine, CA, USA) [20].…”

“…Briefly, after a 30-min period of stabilization (T -30 min), animals received 30-min intravenous infusion of 150 lg/kg/ min Escherichia coli lipopolysaccharide (LPS, serotype 055:B5; Sigma Chemical Co., St. Louis, MO, USA), diluted in 50 ml sterile isotonic saline [20]. Thirty minutes after the end of LPS infusion (T ?…”

Inter-α-Trypsin Inhibitor Attenuates Complement Activation and Complement-Induced Lung Injury

“…Among septic patients, IaI levels were also inversely correlated with physiologic scores and mortality. IaI given prophylactically or therapeutically in animal models of sepsis significantly improved survival (7)(8)(9), but the mechanism of action remains elusive.…”

Protein C and acute inflammation: a clinical and biological perspective

“…In severe sepsis caused by bacteria, fungus, or virus, dysregulation of the hemostatic system may lead to DIC associated with microvascular thrombosis, tissue hypoperfusion, multiorgan failure, and death (45). In animal models of severe sepsis, this characteristic sequence usually causes a procoagulant and antifibrinolytic state within a few hours after onset of the disease (52). In humans, the progression to a full DIC may be rapid or slow depending on the bacterial virulence and the patient's underlying condition.…”