The effect of the thromboxane receptor antagonist BM 13.177 on experimentally induced coronary artery thrombosis in the pig.
We studied the effect of pretreatment with two doses of the thromboxane antagonist BM 13.177 and its solvent on the development of electrically induced coronary artery thrombosis in pigs. Results were compared with those obtained in animals pretreated with intravenously administered acetylsalicylate and its solvent. The effects of both compounds on the overall cardiovascular performance (heart rate, mean arterial blood pressure, cardiac output, systemic vascular resistance) were minimal. In the animals receiving solvent or acetylsalicylate the time to occlusive coronary thrombosis was 33 +/- 4 and 32 +/- 6 min, respectively. BM 13.177, in a dose of 5 mg.kg-1, did not modify the time to thrombotic occlusion (35 +/- 7 min), but in six of the eight animals that had received 10 mg.kg-1 BM 13.177, there was no occlusion within 120 min. In the acetylsalicylate-treated animals, collagen-induced platelet aggregation and plasma thromboxane B2 declined by 72 and 82%, respectively. The decreases were 46 and 20%, respectively, with the higher dose of BM 13.177. It is concluded that, in this porcine model of coronary artery thrombosis, the thromboxane antagonist BM 13.177 effectively suppressed formation of occlusive thrombi whereas acetylsalicylate was ineffective at a dose that lowered arterial thromboxane levels.
van der Giessen
W J
WJ
Laboratory for Experimental Cardiology (Thoraxcenter), Erasmus University Rotterdam, The Netherlands.
Zijlstra
F J
FJ
Berk
L
L
Verdouw
P D
PD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D000889:Anti-Arrhythmia Agents; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013929:Thromboxane B2; C040624:sulotroban; D001241:Aspirin