We have investigated the role of
platelet activating factor (PAF) in the pathogenesis of a murine model of
traumatic shock using
CV-6209, a specific antagonist of PAF.
CV-6209, at a dose of 1 mg/kg (i.v.) given after
trauma, significantly improved survival rate at 150 min and overall survival time. Furthermore, the plasma accumulation of the lysosomal
hydrolase,
cathepsin D, and a cardiotoxic
peptide,
myocardial depressant factor (
MDF), were also attenuated by
CV-6209 in
traumatic shock. Combined treatment employing low doses of
CV-6209 [0.2 mg/kg, i.v. and
prostaglandin (PG) E1, 0.8 microgram/kg/min] in this
shock model was also examined.
CV-6209 (0.2 mg/kg) or
PGE1 (0.8 microgram/kg/min) alone at these doses showed only minimal effects on survival, or plasma
cathepsin D or
MDF activities. However, combined treatment with
CV-6209 (0.2 mg/kg, i.v.) and
PGE1 (0.8 microgram/kg/min) significantly improved survival rate at 150 min, overall survival time, and decreased the accumulation of plasma
MDF. These results suggest that PAF may play an important pathophysiologic role in
traumatic shock in rats. Moreover, combination
therapy using a PAF antagonist and
PGE1 may be useful for the treatment of
traumatic shock.