Selective thromboxane A2 synthetase inhibition in vasospastic angina pectoris.

To investigate whether thromboxane A2 is responsible for the initiation of vasospastic angina pectoris, thromboxane B2 levels were measured in the great cardiac vein and the arterial blood of 12 patients with clinically and angiographically proved vasospastic angina and therapeutic trials were performed with selective thromboxane A2 synthetase inhibitor OKY-046, an imidazole derivative. During ergonovine-provoked (11 cases) and spontaneous (1 case) anginal attacks, great cardiac vein thromboxane B2 increased from 121 +/- 27 to 430 +/- 382 pg/ml (p less than 0.05, n = 12), arterial thromboxane B2 increased from 93 +/- 18 to 122 +/- 33 pg/ml (NS, n = 12) and thromboxane B2 production increased from 3.18 +/- 1.88 to 25.16 +/- 22.32 ng/min (p less than 0.05, n = 6). Subsequently, OKY-046, 400 mg/day orally, was administered to 7 of the 12 patients, while a continuous electrocardiogram was recorded on a dual channel Holter monitor during a 3 day placebo period and the 3 day OKY-046 regimen. Although peripheral plasma thromboxane B2 levels decreased significantly from 98 +/- 15 to 12 +/- 8 and 28 +/- 10 pg/ml (1 and 6 hours after ingestion, respectively) (p less than 0.05 for both), 6-keto-prostaglandin F1 alpha production in serum increased significantly from 0.48 +/- 0.22 to 2.3 +/- 0.72 (1 hour) and 1.8 +/- 0.46 ng/ml (6 hours) (p less than 0.05 for both) during OKY-046 administration.(ABSTRACT TRUNCATED AT 250 WORDS)