Mechanisms of action of PGE1 in hemorrhagic shock in rats.
We studied the effects of prostaglandin E1 (PGE1) in a severe model of hemorrhagic shock in rats. PGE1 was administered as a continuous IV infusion of either 0.1 microgram/kg/min or 1.0 microgram/kg/min starting 30 minutes after the onset of bleeding and continuing until one hour after reinfusion. Hemorrhaged rats treated with PGE1 (1 microgram/kg/min) maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving only the vehicle (ie, 0.9% NaCl) (final MABP 84 +/- 3 vs 57 +/- 4 mm Hg, P less than .01). PGE1 at 1 microgram/kg/min also attenuated the increase in plasma activities of cathepsin D (P less than .01), and at both doses blunted the plasma accumulation of free amino-nitrogen compounds (P less than .02 at 0.1 microgram/kg/min and P less than .01 at 1.0 microgram/kg/min). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in rats treated with PGE1 (1 microgram/kg/min) than in rats receiving the vehicle (35 +/- 4 U/mL vs 74 +/- 12 U/mL, P less than .01). Rats receiving PGE1 (1.0 microgram/kg/min) also exhibited a significantly increased survival rate (P less than .01) and post-reinfusion survival time (P less than .01) compared with rats receiving only the vehicle. Our data suggest that antiproteolytic and membrane-stabilizing actions of PGE1 are important and may contribute to its beneficial effects in hemorrhagic shock. Other mechanisms (eg, inhibition of platelet aggregation and vasodilation) may also be involved.
Bitterman
H
H
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Stahl
G L
GL
Terashita
Z
Z
Lefer
A M
AM
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D002854:Chromatography, Paper; D004353:Drug Evaluation, Preclinical; D007262:Infusions, Intravenous; D008297:Male; D009584:Nitrogen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D002402:Cathepsin D; D000527:Alprostadil; D009584:Nitrogen