RESTING MYOCARDIAL ISCHEMIA AFTER INTRAVENOUS INFUSION OF BM 13.177, A THROMBOXANE RECEPTOR ANTAGONIST

We conducted a double blind placebo controlled trial of BM 13.177, a thromboxane receptor antagonist, given intravenously in patients (PTS) with stenoses >70 % of the left anterior descending coronary artery and stable exertional angina pectoris (AP). The study had to be stopped after enrollment of 8 PTS, because 2 had developed resting AP after initiation of the study medication. Both proved to belong to the 4 PTS who had received BM 13.177 (12.5 mg/min). While in one PT, AP was mild, transient and associated with only slight decreases in coronary sinus blood flow (CSBF) and myocardial lactate extraction (MLE), in the other, AP was severe and persisted for 30 minutes in spite of antianginal therapy. Severe clinical symptoms in this PT were associated with a marked fall in MLE from +24 to -121 %. Two PTS under BM 13.177 and 4 on placebo underwent supraventricular stimulation. For both groups, no change in clinical symptoms, CSBF or MLE occured in comparison to a former control stimulation without medication. BM 13.177 led to an inhibition of ex vivo platelet aggregation induced by collagen 1 pg/ml (mean reduction in rate of aggregation by 41 %, p< 0.05), while aggregation was not influenced with collagen 5 μg/ml or ADP. This effect of BM on platelets is explained by its thromboxane receptor blocking properties. The induction of resting myocardial ischemia, however, in 2 of 4 PTS with formerly stable exertional AP may have been the result of either a coronary steal mechanism or an intrinsic stimulation of vascular thromboxane receptors, followed by coronary vasoconstriction.