The effect of the thromboxane A₂ receptor antagonist SQ 29,548 on the severity of pacing-induced ischemia

Summary

The effect of the thromboxane A₂ (TXA₂)/prostaglandin endoperoxide receptor antagonist, SQ 29,548 on pacing-induced ischemia was determined in anesthetized open-chest dogs. The dogs were subjected to a left anterior descending coronary artery (LAD) stenosis sufficient to result in ischemia as measured by epicardial ST-segment elevation only when the hearts were paced 70–80 beats/min above baseline. After a recovery (nonpacing) period, either 0.2 mg/kg+0.2 mg/kg/hr SQ29,548 or saline was infused i.v. The animals were subjceted to 5 min periods of pacing before and 10, 40 or 70 min after the initiation of drug or saline treatment. Before drug treatment, pacing+LAD stenosis resulted in significant ST-elevation in both groups (11.5±1.1 mV and 12.4±0.6 mV for saline and SQ 29,548 groups, respectively). During drug treatment, SQ 29,548 significantly reduced ST-elevation during pacing+stenosis at 40 and 70 min. At 70 min, ST-elevation was 4.9±1.7 mV for the SQ 29,548 group vs 10.8±1.2 mV for the saline group (p<0.05). In separate experiments 0.2 mg/kg+0.2 mg/kg/hr SQ 29,548 antagonized the activity of a TXA₂ mimetic, U-46,619, for femoral vasoconstriction, causing 100-to-200 fold rightward shifts in dose response relationships. Thus, a dose of SQ 29,548 capable of strong TXA₂-receptor blockade reduced the scverity of ischemia, and this effect was independent of changes in arterial blood pressure and heart rate.