Effect of the Combination of Anticoagulant and Thromboxane Synthetase Inhibitor (Y-20811) or Receptor Blockade (S-1452) on Preventing Thrombotic Cyclic Coronary Flow Reduction in Dogs with Coronary Stenosis.

We examined the hypothesis that combined actions of anticoagulant (heparin) and Y-20811, thromboxane A2 synthetase inhibitor (TXSI), or S-1452, receptor blockade (TXRB), can provide better antithrombotic protection than TXSI or TXRB alone. In 20 of 33 dogs instrumented, placement of a critical stenosis at a focus of coronary vascular injury initiated a reproducible cyclic coronary flow reduction (CCFR). TXSI (1 mg/kg, IV) perfectly inhibited CCFR in 6 of 10 dogs (60%), and was associated with a significant decrease in 11-dehydro-TXB2 (85 +/- 8% of control; p < 0.05) and an increase in 6-keto-PGF1 alpha (155 +/- 38%; p < 0.05) in coronary sinus blood samples. In the remaining 4 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. On the other hand, TXRB (1 mg/kg, IV) perfectly inhibited CCFR in 7 of 10 dogs (70%), and was accompanied by a significant increase in 6-keto-PGF1 alpha (214 +/- 65%; p < 0.05) and unchanged TXB2 level. In the remaining 3 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. Thus, the combination of anticoagulant and TXSI or TXRB were more effective than TXSI or TXRB alone in abolishing thrombotic CCFR, suggesting that the combination might be effective for treating patients with impending myocardial infarction.