thromboxane-a2 and Angina-Pectoris--Variant

Topics: Angina Pectoris, Variant; Catecholamines; Coronary Circulation; Coronary Disease; Coronary Vasospasm; Humans; Myocardial Infarction; Oxygen; Oxygen Consumption; Thromboxane A2

Topics: Angina Pectoris, Variant; Coronary Circulation; Epoprostenol; Homeostasis; Humans; Muscle Tonus; Muscle, Smooth, Vascular; Platelet Aggregation; Prostaglandins; Thromboxane A2; Thromboxane B2; Thromboxanes

Topics: Angina Pectoris, Variant; Animals; Cardiac Catheterization; Coronary Vasospasm; Dogs; Epoprostenol; Ergonovine; Humans; Myocardial Infarction; Nitroglycerin; Platelet Aggregation; Receptors, Adrenergic, alpha; Thromboxane A2

Topics: Angina Pectoris; Angina Pectoris, Variant; Coronary Disease; Coronary Vasospasm; Humans; Prostanoic Acids; Stress, Physiological; Thromboxane A2; Vasoconstriction; Vasodilation

Topics: Angina Pectoris; Angina Pectoris, Variant; Blood Platelets; Coronary Disease; Death, Sudden; Diet; Epoprostenol; Humans; Muscle, Smooth, Vascular; Myocardial Infarction; Platelet Aggregation; Risk; Smoking; Thromboxane A2

To test the hypothesis that intracoronary concentrations of thromboxane (Tx)A2 could influence the response to cold pressor test (CPT) in variant angina, great cardiac vein blood flow (by thermodilution) and the concentration of TxB2 (the stable metabolite of TxA2) in the great cardiac vein and aorta were measured under control conditions and during CPT in 14 patients with angina at rest associated with transient ST-segment elevation in the anterior leads. In seven patients pretreated with aspirin (intravenous administration of 3.6 mg/kg lysine salt of acetylsalicylic acid, corresponding to 2 mg/kg aspirin), TxB2 baseline concentrations were lower in both the great cardiac vein (47 +/- 19 vs 176 +/- 88 pg/ml; p less than 0.005) and the aorta (45 +/- 16 vs 109 +/- 56 pg/ml, p less than 0.02) than in seven patients who were not taking cyclooxygenase inhibitors. In the two groups, great cardiac vein flow and anterior region coronary resistance were similar under control conditions. During CPT anterior region coronary resistance increased in patients pretreated with aspirin (from 1.97 +/- 0.99 to 2.22 +/- 1.11 mm Hg/ml/min; p less than 0.02) and in patients without aspirin pretreatment (from 1.94 +/- 0.43 to 2.06 +/- 0.34 mm Hg/ml/min; p less than 0.05), and the difference between the two groups was not statistically significant. Therefore the vasoconstrictor response of coronary vessels to CPT in variant angina is not influenced by the intracoronary TxB2 concentrations and is not modified by aspirin pretreatment.

Topics: Adult; Angina Pectoris, Variant; Angiography; Aorta; Aspirin; Blood Pressure; Cold Temperature; Coronary Circulation; Hemodynamics; Humans; Male; Middle Aged; Osmolar Concentration; Thromboxane A2; Thromboxane B2; Vasoconstriction

Thromboxane A2 (TxA2), an arachidonic acid metabolite causing vasoconstriction and platelet aggregation, is a putative mediator of coronary-artery vasospasm. To determine whether platelet-released TxA2 causes coronary arterial vasospasm, we measured plasma thromboxane B2 (TxB2, the inactive hydration product of TxA2) in the radial-artery and coronary-sinus blood of seven patients and performed therapeutic trials of antiplatelet agents in nine. Although coronary-sinus TxB2 levels rose from the base line approximately fivefold with spontaneous ischemia, samples drawn early in ischemia showed no rise over base-line values. Although a 150 mg dose of aspirin reduced urinary dinor-TxB2 levels by over 75 per cent, it had no effect on the course of the chronic recurrent form of angina pectoris due to vasospasm ("vasotonic angina"). Similarly, indomethacin had no effect on the frequency or duration of ischemia. TxA2 is unlikely to cause vasotonic angina, but it may be released during coronary vasospasm.

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Arteries; Aspirin; Clinical Trials as Topic; Coronary Circulation; Coronary Vessels; Double-Blind Method; Female; Humans; Indomethacin; Ischemia; Male; Middle Aged; Recurrence; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors; Veins

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

To elucidate the contribution of prostanoids in coronary spasm, plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha at the coronary sinus and ascending aorta in 21 patients with variant angina were measured, as compared with findings in 20 with effort angina and 13 subjects with normal coronaries. In the coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. On the contrary, the data obtained from patients with variant angina were not statistically significant. However, eight patients whose coronary angiogram revealed more than 50% of coronary stenoses had statistically significant high levels of TXB2 and other patients with normal coronaries or less than 50% of narrowing showed almost the same levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in patients with variant angina were very low in both groups with variant angina. These data suggest that high levels of TXB2 observed in patients with atherosclerotic coronaries may be an accelerating factor while low levels of prostacyclin may be an essential factor leading to spasm. HLA analysis of 23 patients with variant angina was performed to search for genetic factors, under the hypothesis that such may contribute to the low levels in prostacyclin. This preliminary study revealed statistically significant high frequencies of Bw52 and B-40 in the patients, as compared with frequencies among 152 normal Japanese. Genetic studies are ongoing in our clinic.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Angina Pectoris, Variant; Coronary Vasospasm; Electrocardiography; Female; Histocompatibility Antigens Class II; HLA Antigens; Humans; Male; Middle Aged; Thromboxane A2; Thromboxane B2; Thromboxanes

Topics: Adult; Aged; Angina Pectoris; Angina Pectoris, Variant; Angina, Unstable; Aorta; Aspirin; Blood Pressure; Coronary Circulation; Coronary Disease; Coronary Vessels; Epoprostenol; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Prostaglandins; Thromboxane A2; Thromboxane B2

Topics: Angina Pectoris; Angina Pectoris, Variant; Animals; Aspirin; Blood Platelets; Coronary Circulation; Dogs; Epoprostenol; Humans; Indomethacin; Platelet Aggregation; Thromboxane A2; Thromboxane B2; Thromboxanes

To examine plasma levels of vasoconstrictive prostanoid (thromboxane A2) in patients with coronary artery disease, amounts of its product, thromboxane B2, in acidic lipid extracts from plasma were determined by a radioimmunoassay. Peripheral venous samples were obtained in 14 normal subjects and 12 patients with coronary artery disease, and simultaneous aortic and coronary sinus blood samples were obtained at rest, during pacing, and after pacing in eight cases who were subjected to atrial pacing stress test. Mean thromboxane B2 levels in peripheral venous blood in 14 normal subjects were found to be 243 +/- 96 pg/ml. Of nine cases with angina pectoris on effort (angiographically documented severe coronary artery stenosis), five exhibited increased thromboxane B2 levels in peripheral plasma. Three cases of a variant form of angina pectoris exhibited pronounced increases in peripheral thromboxane B2 levels. Of eight cases subjected to atrial pacing stress test, three exhibited marked increases in thromboxane B2 levels in coronary sinus effluent at peak pacing, two of which were accompanied by typical anginal pain during the test. These findings suggest that increased thromboxane A2 production may be associated with altered thromboxane metabolism. This may occur because of altered interactions between functions of vascular wall and blood platelets within coronary circulation in patients with coronary artery disease.

Topics: Angina Pectoris; Angina Pectoris, Variant; Cardiac Pacing, Artificial; Coronary Disease; Humans; Male; Radioimmunoassay; Thromboxane A2; Thromboxane B2; Thromboxanes