Protective effects of thromboxane receptor blockade in splanchnic artery occlusion shock.
Splanchnic artery occlusion (SAO) followed by release of the occlusive clamps produces circulatory shock characterized by an abrupt hypotension, cardiac depression and high lethality. We studied the effects of the thromboxane receptor antagonist, BM-13505, in rats during SAO shock. 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 within 90-120 minutes of release of the occlusion. BM-13505 was started at reperfusion for 10 minutes. SAO shock rats treated with BM-13505 (1 mg/kg) maintained post-reperfusion mean arterial blood pressure (MABP) at significantly higher values compared to those receiving only the vehicle (0.9% NaCl). Treatment with BM-13505 attenuated the plasma activity of the lysosomal protease cathepsin D (p less than 0.05 from vehicle) and the plasma accumulation of free amino-nitrogen compounds (p less than 0.01 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in BM-13505 treated rats than in non-treated rats (p less than 0.01 from vehicle). SAO shock rats treated with BM-13505 also exhibited a higher survival rate than the vehicle group (75% vs. 20%). These results suggest an important role of thromboxane A2 in the pathophysiology of SAO shock.
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
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Aoki
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Lefer
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D004195:Disease Models, Animal; D006400:Hematocrit; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000503:physiopathology*; D009201:Myocardial Depressant Factor / Q000097:blood; D009584:Nitrogen / Q000097:blood; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000503:physiopathology*; D013152:Splanchnic Circulation; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D009201:Myocardial Depressant Factor; D010648:Phenylacetates; D013449:Sulfonamides; D013928:Thromboxane A2; D002402:Cathepsin D; D009584:Nitrogen; C051762:daltroban