Protective effects of CG-4203, a novel stable prostacyclin analog, in traumatic shock.
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.
Bitterman
H
H
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Stahl
G L
GL
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D009201:Myocardial Depressant Factor; C039188:taprostene; D011464:Epoprostenol; D002402:Cathepsin D