2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic-acid and Coronary-Vasospasm

To clarify the role of thromboxane A2 (TXA2) in evoking coronary spasm, we compared coronary arterial spasticity induced by ergonovine maleate (EM) with coronary sinus thromboxane B2 (TXB2: a stable catabolite of TXA2) in 34 patients with documented variant angina and 11 patients with chest pain syndrome (CPS). We also examined the effect of OKY-1581 (8 mg/kg, i.v.), a TXA2 synthetase inhibitor, on the coronary arterial spasticity of these patients. When blood samples were taken from coronary sinus just before EM test, all patients with variant angina exhibiting markedly augmented TXB2 levels (424 +/- 138 pg/ml), had positive EM test results, while CPS exhibiting lower TXB2 levels (223 +/- 38 pg/ml), had negative EM test. We found that the amounts of EM needed to induce coronary spasm were inversely correlated with TXB2 levels in coronary sinus. In 7 out of these 8 patients, OKY-1581 was found to attenuate the increased spasticity with reduction of coronary sinus TXB2 levels. In 3 patients, an EM rechallenge at symptomatically quiescent stage resulted in negative test with augmented TXB2 levels being markedly decreased. These findings indicate that increased TXA2 in circulating plasma is closely correlated with the hypersensitivity of coronary arteries to EM in patients with variant angina, suggesting a possible role of augmented TXA2 production in the enhancement of coronary vascular spasticity.

Topics: Adult; Aged; Angina Pectoris, Variant; Coronary Circulation; Coronary Vasospasm; Ergonovine; Female; Humans; Male; Methacrylates; Middle Aged; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase