Anti-shock properties of the prostacyclin analog, iloprost, in traumatic shock.
The effects of iloprost, a synthetic carbacyclin derivative of prostacyclin (PGI2) was studied in a standardized model of traumatic shock. Pentobarbital anesthetized rats (35 mg/kg) subjected to Noble-Collip drum trauma were characterized by a 84 +/- 10 minute survival time, a 16-fold increase in plasma cathepsin D activity, and a 5-fold increase in plasma myocardial depressant factor (MDF) activity. Iloprost significantly attenuated the accumulation of MDF activity in the plasma (69 +/- 14 vs. 20 +/- 6 U/ml) vehicle vs. drug (p less than 0.01), respectively, and significantly prolonged survival time to 243 +/- 36 minutes (p less than 0.01). Plasma cathepsin D activity was also significantly attenuated (12 +/- 1.8 vs. 6.2 +/- 2.1 U/ml), vehicle vs. drug, respectively (p less than 0.02). Iloprost exhibited significant anti-proteolytic activity in pancreatic homogenates. Iloprost appears to exert a membrane stabilizing effect decreasing plasma cathepsin D activity and attenuating MDF production, probably secondarily to its anti-proteolytic effect and its maintenance of the splanchnic circulation. Iloprost may therefore prove to be a useful therapeutic agent in acute ischemic disorders including traumatic shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology / Q000627:therapeutic use*; D016285:Iloprost; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012774:Shock, Traumatic / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*
D009201:Myocardial Depressant Factor; D011464:Epoprostenol; D002402:Cathepsin D; D016285:Iloprost