Effects of prostacyclin and taprostene in splanchnic artery occlusion shock.
Prostacyclin (PGI2) and taprostene (CG-4203) were studied in a highly lethal model of splanchnic artery occlusion (SAO) shock in pentobarbital anesthetized rats. Total occlusion of the superior mesenteric and celiac arteries for 40 min resulted in a severe shock state often resulting in a fatal outcome within 2 h following release of the occlusion. PGI2 or taprostene was infused at a rate of 100 ng/kg/min commencing at occlusion of the celiac and superior mesenteric arteries. Taprostene significantly improved survival time and taprostene treated animals maintained post-reperfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving taprostene vehicle (final MABP 96 +/- 3 vs 45 +/- 3.5 mmHg, p less than 0.001, respectively). In addition, taprostene significantly (p less than 0.05) attenuated the rise in hematocrit in SAO shock and the activity of plasma cathepsin D (p less than 0.005 from SAO vehicle). Taprostene also tended to decrease the accumulation of free amino-nitrogen compounds, but not significantly. In contrast, PGI2 neither improved survival time and the maintenance of post-reperfusion MABP, nor attenuated the rise in hematocrit, the plasma accumulation of free amino-nitrogen compounds, or plasma cathepsin D activity. These findings suggest that taprostene may possess greater cytoprotective properties than PGI2.
VanAntwerp
D R
DR
Department of Cardiovascular Pharmacology, Syntex Research, Palo Alto, CA 94304.
Hedley
L R
LR
Spires
D A
DA
Strosberg
A M
AM
Johnson
G
G
Lefer
A M
AM
D000818:Animals; D002402:Cathepsin D / Q000097:blood; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006400:Hematocrit; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries; D008641:Mesenteric Vascular Occlusion / Q000150:complications / Q000188:drug therapy*; D009584:Nitrogen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000188:drug therapy* / Q000209:etiology
C039188:taprostene; D011464:Epoprostenol; D002402:Cathepsin D; D009584:Nitrogen