Experimental Coronary Artery Thrombosis in the Absence of Thromboxane A2 Synthesis

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Abstract
The actions of the thromboxane synthetase inhibitor, U-63557A. wore evaluated in vivo in anesthetized open-chest dogs by inducing left circumflex coronary artery (LCCA) thrombosis with low amperage electrical stimulation (100 μA for 6 h) of the intimal surface of the vessel, and ex vivo by assessing platelet aggregation and TXB2 production. U-63557A, 10 mg/kg × 5 mg/kg/h i. v., reduced ex vivo platelet aggregation in response to arachidonic acid (0.65 mM) by 93 + 2% (p < 0.05. ± SEM), whereas the concurrent formation of TXB2 was decreased by 78 + 8% (p < 0.05). TXB2 concentration also was reduced significantly in vivo as measured from coronary sinus blood samples; however. 6-keto-PGF concentration was unchanged from predrug values. Despite the significant inhibiton of platelet aggregation and TXB2 production, thrombus mass was not reduced: control, 32.0 + 5.9 mg (n 7): U-63557A. 30.8 × 12.0 mg (n 5, p NS). These results suggest that U-63557A effectively inhibits TXA2 synthetase. but lacks antithrombotic activity in our experimental model. Therefore, substances other than TXA2 may be capable of mediating occlusive coronary artery thrombosis.