Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Abstract

In order to elucidate the role of endogenous thromboxane A2 in myocardial ischaemia, cats were subjected to 5 h of permanent occlusion of the left anterior descending coronary artery (LAD) and treated with the thromboxane receptor antagonist BM 13.177 (5 mg kg−1 h−1, i.v.). In comparison with vehicle‐treated LAD‐occluded cats, BM 13.177 significantly attenuated the loss of creatine phosphokinase‐specific activity from the ischaemic myocardium and antagonized the ischaemia‐induced rise in the ST‐segment of the electrocardiogram. BM 13.177 at the dose used did not reduce plasma thromboxane levels or ischaemia‐induced platelet aggregate formation but considerably antagonized thromboxane‐dependent platelet secretion ex vivo. The study demonstrates some beneficial effects of selective blockade of thromboxane receptors on biochemical and electrophysiological parameters of acute myocardial ischaemia.

Roles of Prostaglandin I 2 and Thromboxane A 2 in Cardiac Ischemia-Reperfusion Injury

“…29 Conversely, there are controversial reports regarding the cardioprotective effect of TP antagonists. Although beneficial effects of TP antagonists have been reported, 16 an absence of their protective effects on cardiac I/R injury has also been reported. 17 This discrepancy may result from the fact that some TP antagonists cross-act on other prostanoid receptors, such as EP 3 , 30 through which PGE 2 was reported to exert protective effects on cardiac I/R injury.…”

“…14 -16 The beneficial effects of TX synthase inhibitors on cardiac I/R injury were attributed to enhanced generation of PGI 2 derived from increased availability of its precursor, resulting in inhibition of neutrophil adhesion to endothelial cells. 14,15,17 The cardioprotective effects of TP antagonists, however, are variable, according to the reports, 16,17 and therefore, the role of TXA 2 in I/R injury has not been established.…”

Endothelin‐1 inhibits platelet aggregation in vivo: a study with 111indium‐labelled platelets

“…vascular trauma associated with surgery; vascular instrumentation by catheters) resulting in endothelial cell damage, enhanced thromboxane B2 plasma levels, as well as thrombocytopenia which may therefore artificially influence platelet function in vivo (Schror & Thiemermann, 1986).…”

Additive Beneficial Effects of Two Inhibitors of Vasoconstrictor Mediators in Acute Myocardial Ischemia

“…Coronary vasospasm, platelet aggregation, and loss of myocardial cell integrity induced by increased localized production of TxA2 could propagate ischemic damage once myocardial ischemia is initiated. In this regard, thromboxane synthetase inhibitors and thromboxane receptor antagonists have been reported to reduce the ischemic damage to the myocardium after acute coronary artery ligation (12)(13)(14).…”