Protective effects of CG-4203, a novel stable prostacyclin analog, in traumatic shock.

Abstract

We studied the effects of CG-4203, a novel stable prostacyclin analog, in a severe model of traumatic shock in rats. Traumatic shock was produced by Noble Collip drum trauma and was characterized by marked hypotension, a 4- to 5-fold increase in plasma cathepsin D and myocardial depressant factor activities, and survival time of 95 +/- 15 minutes. Treatment with CG-4203 (100 ng/kg/min) significantly prolonged survival time to 194 +/- 20 min (p less than 0.002). Traumatized rats treated with CG-4203 exhibited significantly lower plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05). Furthermore, the plasma accumulation of myocardial depressant factor (MDF) activity was also significantly blunted in traumatized CG-4203 treated rats when compared with traumatized rats receiving only the vehicle (p less than 0.01). Our results suggest that a combination of membrane stabilizing and anti-proteolytic effects and inhibition of platelet aggregation may mediate the protective effects of CG-4203 in traumatic shock.

• Authors: H Bitterman, G L Stahl, A M Lefer
• Journal: Prostaglandins (Prostaglandins) Vol. 35 Issue 1 Pg. 41-50 (Jan 1988) ISSN: 0090-6980 [Print] United States
• PMID: 3287456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Myocardial Depressant Factor
• taprostene
• Epoprostenol
• Cathepsin D

Topics

• Animals
• Blood Pressure (drug effects)
• Cathepsin D (blood)
• Disease Models, Animal
• Epoprostenol (therapeutic use)
• Lysosomes (enzymology)
• Male
• Myocardial Depressant Factor (blood)
• Rats
• Rats, Inbred Strains
• Reference Values
• Shock, Hemorrhagic (drug therapy)