Beneficial mechanisms of action of a prostacyclin enhancing agent in splanchnic artery occlusion shock.
Defibrotide stimulates PGI2 production and exerts significant antithrombotic, fibrinolytic and plasminogen-activating activities. We studied its effects in splanchnic artery occlusion (SAO) shock in rats. Anesthetized rats subjected to total occlusion of the celiac and superior mesenteric arteries for 40 minutes developed a severe shock state following reperfusion usually resulting in death 90-120 minutes after releasing the clamps. Defibrotide 910 mg/kg +25 mg/kg/h) treated SAO shock rats maintained higher post-reperfusion mean arterial blood pressure compared to those receiving only the vehicle (0.9% NaCl). SAO shock rats treated with defibrotide exhibited lower plasma activities of the lysosomal protease cathepsin D (p less than 0.05 from vehicle) and myocardial depressant factor (p less than 0.02 from vehicle) as well as the plasma accumulation of free amino-nitrogen compounds (p less than 0.05 from vehicle). All SAO shock rats treated with defibrotide survived the entire 120 post-release period compared with only a 42% survival rate for rats receiving only the vehicle (p less than 0.02). These results suggest a remarkable protective effect of defibrotide in SAO shock.
Aoki
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N
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Siegfried
M
M
Tsao
P
P
Lento
P
P
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy*; D009201:Myocardial Depressant Factor / Q000097:blood; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000188:drug therapy* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects*
D005343:Fibrinolytic Agents; D009201:Myocardial Depressant Factor; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D002402:Cathepsin D