Tuesday August 19, 2008
Does Xigris help in ALI ?

See this interesting work done on sheeps.

Introduction: Acute lung injury (ALI) often complicates severe sepsis. Recombinant human activated protein C (rhAPC) - Xigris, with its anti-coagulant, anti-inflammatory, fibrinolytic and anti-apoptotic effects, reportedly reduces respirator-dependent days and mortality of patients with severe sepsis.

Methods: Two groups of sheep were exposed to Escherichia coli endotoxin (lipopolysaccharide; LPS) 15 ng/kg/min intravenously from 0 to 24 hours;

• one group received only LPS throughout (n = 8) and
• the other group received LPS in combination with rhAPC 24 mug/kg/hr from 4 to 24 hours (n = 9)

In addition,

• one group received rhAPC as above as the only intervention (n = 4) and
• four sham-operated sheep were used for determination of alpha and epsilon-isoforms of protein kinase C (PKC alpha, epsilon) in pulmonary tissue

Results

• Infusion of endotoxin caused lung injury manifested by increments in pulmonary artery pressure, pulmonary micro-occlusion pressure, pulmonary vascular downstream resistance, pulmonary vascular permeability index, extravascular lung water index (EVLWI) and deterioration of oxygenation that were all attenuated by infusion of rhAPC
• Endotoxemia led to changes in inflammation and coagulation, including pulmonary neutrophil accumulation paralleled by increased tumor necrosis factor-alpha and decreased protein C and fibrinogen in animal plasma, that all improved following infusion of rhAPC
• Moreover, rhAPC prevented the translocation of PKC alpha, epsilon from the cytosolic fraction of lung tissue extracts

Conclusions: In awake sheep, rhAPC alleviates endotoxin-induced lung injury, as characterized by improvements of oxygenation, coagulation and inflammation, as well as by reversal of pulmonary hemodynamic - and volumetric changes.

Reference: Click to get article

Recombinant human activated protein C attenuates endotoxin-induced lung injury in awake sheep Critical Care 2008, 12:R104