thromboxane-b2 and Angina-Pectoris--Variant

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

One of the causes of coronary artery spasm in patients with variant angina could be a disturbed interaction between the vasodilating action of endothelial derived relaxing factor and the vasospastic action of neuropeptide Y and thromboxane B2. The aim of this study was a verification of the participation of neuropeptide Y and thromboxane B2 in etiopathogenesis of the coronary artery spasm in patients with variant angina. The survey was made in 38 patients with variant angina and in 18 patients with chronic stable angina pectoris. The control group consisted of 20 healthy persons. Before the hyperventilation test, during which the person under test has been breathing with a frequency of 40/minute through 5 minutes, the Tris (tromethamol) of pH = 10.5 has been given in intravenous infusion lasting for 5 minutes. The neuropeptide Y and thromboxane B2 plasma levels have been determined just before the hyperventilation test, just after the termination of the test and 10 minutes after the termination of the test. Neuropeptide Y and thromboxane B2 plasma levels have been determined with a radioimmunologic method. It has been recorded that during the hyperventilation test in all of the 38 patients with variant angina the clinical and the electrocardiographic symptoms of the coronary artery spasm have appeared--but these have not appeared in patients with chronic stable angina pectoris and in healthy persons. The level of neuropeptide Y in patients with variant angina before the test, just at its end and as well as 10 min. after completing of the hyperventilation test, was significantly higher compared with the level in patients with chronic stable angina pectoris and controls. Contrary to chronic stable angina pectoris patients and controls, in variant angina group the level of neuropeptide Y increased rapidly at the end of the test and further elevation in neuropeptide Y level was observed 10 min. after the test. There was no difference in basal thromboxane B2 levels between angina patients and controls. At the end of hyperventilation test in variant angina group thromboxane B2 level significantly increased and remained on this level until 10 min. after the test. Significant increase of neuropeptide Y and thromboxane B2 plasma levels in variant angina patients during artery coronary spasm induced by hyperventilation test suggests the contribution of these humoral factors to the pathogenesis of vasospastic episodes in angina patients.

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Chronic Disease; Female; Humans; Male; Middle Aged; Neuropeptide Y; Thromboxane B2

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

Topics: Angina Pectoris, Variant; Clinical Trials as Topic; Humans; Thromboxane B2

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)

Topics: Acrylates; Administration, Oral; Adult; Aged; Angina Pectoris, Variant; Aorta; Cardiac Catheterization; Coronary Vessels; Electrocardiography; Humans; Male; Methacrylates; Middle Aged; Thromboxane B2; Thromboxane-A Synthase

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

This study aimed to assess the association between adherence to the Mediterranean diet with serum Nitric oxide, Prostacyclin, and Thromboxane B

Topics: Angina Pectoris, Variant; Case-Control Studies; Diet, Mediterranean; Epoprostenol; Humans; Nitric Oxide; Thromboxane B2; Vegetables

The blood levels of 6-keto-PGE1 alpha and thromboxane B2 were measured in the coronary sinus of 15 males during and just after a spontaneous myocardial ischemic episode. The comparison was made in 30 males with coronary heart disease in the presence of exercise-induced angina in whom coronary sinus blood samples were taken during myocardial ischemia provoked by pacing and 6 males suffering from cardialgias without signs of coronary atherosclerosis. The patients with spontaneous anginal attacks had lower baseline 6-keto-PGE1 alpha (179.0 +/- 47.8 pkg/ml) than those with exercise-induced angina (336.0 +/- 65.7 pkg/ml; p less than 0.1). This difference became greater during ischemia (165.0 +/- 49.0 and 350.0 +/- 69.5 pkg/ml, respectively, p less than 0.05) and just after its elimination (166.0 +/- 48.7 and 413.0 +/- 76.0 pkg/ml, respectively, p less than 0.05). Coronary sinus blood thromboxane B2 levels were not substantially different in the presence or absence of myocardial ischemia. Thus, a decrease in the prostacyclin-forming function of the coronary endothelium plays a definite role in the genesis of spontaneous myocardial ischemic episodes.

Topics: Adult; Alprostadil; Angina Pectoris; Angina Pectoris, Variant; Coronary Vessels; Electrocardiography; Electrocardiography, Ambulatory; Epoprostenol; Exercise Test; Humans; Male; Middle Aged; Thromboxane B2; 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

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris, Variant; Coronary Vasospasm; Humans; Middle Aged; Thromboxane B2

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

Plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha in the blood samples taken at the coronary sinus and ascending aorta from twenty-one Japanese patients with variant angina and twenty with effort angina were measured by radioimmunoassay, the objective being to search for the contribution of prostanoids in coronary spasm. The data were compared with data on thirteen subjects free from coronary artery diseases. In coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. These with variant angina also had high levels, albeit without a statistically significant difference. Eight patients with variant angina and for whom the coronary angiogram showed more than 50% of narrowing had statistically significant high levels of TXB2, and the other thirteen with variant angina and normal coronaries or less than 50% of narrowing had the same plasma levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in both coronary sinus and aortic blood of patients with variant angina were very low, as compared with normal controls. Statistically significant low levels of 6-keto PGF1 alpha were noted in the coronary sinus blood of patients with variant angina with normal coronaries and in the aortic blood of those with variant angina, as compared with data on the normal controls. Neither ergonovine test nor spontaneous attacks in patients with variant angina revealed characteristic changes in levels of TXB2 and 6-keto PGF1 alpha in the coronary sinus. These data suggest that high levels of TXB2 in patients with atherosclerotic coronaries may be one factor leading to spasm, while low levels of PGI2 may be a contributing factor.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris, Variant; Arteriosclerosis; Coronary Vessels; Ergonovine; Exercise Test; Female; Humans; Male; Middle Aged; Thromboxane B2

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

We used a validated radioimmunoassay to examine plasma thromboxane B2 (TxB2) levels in 6 consecutive vasotonic angina (VA) patients, 14 patients with fixed, occlusive coronary artery (VO) disease and 9 healthy volunteers. In the latter groups, basal TxB2 release was absent. However, all 6 VA patients showed basal release. In one, sustained levels of up to 12 pmol/ml over 2 months of clinical instability were found. Daily aspirin rendered TxB2 undetectable with clinical improvement. In a second patient, angina coincided with up to 14 pmol/ml of TxB2 in peripheral blood, and myocardial infarction produced still further increases. The 14 VO patients were then studied by rapid atrial pacing to detect TxB2 release coinciding with pacing-induced angina and myocardial lactate production. All demonstrated significant occlusive disease (2.5 critical lesions per patient). Blood was taken simultaneously from coronary sinus (CS) and brachial artery (BA) catheters for lactate and TxB2 analysis before, immediately after and 10 min after pacing-induced ischemia. Lactate extraction fell from 29.3 +/- 3.7 per cent to -21.1 +/- 12.8 per cent to -74.3 +/- 20.3 per cent during pacing (all p less than 0.01) but was normal in 10 min (25.1 +/- 3.55). CS TxB2 rose from 18 per cent to 204 per cent of control during pacing but was absent after 10 min. BA TxB2 rose from 40 per cent to 132 per cent of control during and after pacing, but was absent after 10 min (p less than 0.05). In VA, TxB2 is uniquely, continuously present in peripheral blood and levels rise further during symptomatic intervals and myocardial infarction. In VO, even CS TxB2 is absent at rest, and rises less rapidly than in VA, even during pacing-induced ischemia. Although antiplatelet agent will block all TxB2 release even in VO, their clinical potential seems greatest in VA.

Topics: Angina Pectoris; Angina Pectoris, Variant; Arterial Occlusive Diseases; Aspirin; Blood Platelets; Cardiac Pacing, Artificial; Coronary Disease; Coronary Vasospasm; Heparin; Humans; Lactates; Thromboxane B2; Thromboxanes

Current concepts of atherogenesis, based on animal models, suggest a role for platelets in the development of atherosclerotic lesions, possibly through the release of alpha granule constituents. Platelets may also contribute to the development of vascular spasm through thromboxane A2 production. Platelet activation in the coronary circulation in patients with coronary artery disease (CAD) should occur if these hypotheses apply clinically. We measured aortic and coronary sinus plasma levels of the platelet alpha granule constituent beta-thromboglobulin (B-TG) and thromboxane B2 (TX B2) by radioimmunoassay in 15 patients with severe atherosclerotic CAD, seven patients with angiographically normal coronaries, and five patients undergoing evaluation for coronary artery spasm (CAS). Compared with the controls, CAD patients had significantly greater transmyocardial release of B-TG (11.1 +/- 8.1 ng/ml, mean +/- SEM vs 62.5 17.2, p less than 0.05 by rank sum test); TX B2 gradients showed a similar trend but the difference was not statistically significant (-0.08 +/- 0.03 ng/ml vs 0.22 +/- 0.02, 0.05 less than p less than 0.10). Three of the five patients studied developed CAS which was associated with acute elevation in coronary sinus TX B2; the two non-CAS patients with drug provocation had undetectable coronary sinus TX B2. We conclude that abnormal platelet activation takes place in the coronary circulation of CAD patients, and that production of acute myocardial ischemia by CAS occurs with increased coronary sinus TX B2.

Topics: Angina Pectoris; Angina Pectoris, Variant; beta-Thromboglobulin; Blood Platelets; Catheterization; Coronary Angiography; Coronary Disease; Humans; 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

Topics: Adult; Aged; Angina Pectoris; Angina Pectoris, Variant; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Coronary Vasospasm; Female; Humans; Male; Middle Aged; 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

Topics: Angina Pectoris; Angina Pectoris, Variant; Fatty Acids, Nonesterified; Female; Heparin; Humans; Injections, Intravenous; Male; Platelet Aggregation; Thromboxane B2; Thromboxanes

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Coronary Disease; Female; Humans; Male; Middle Aged; Radioimmunoassay; Rest; Thromboxane B2; Thromboxanes

The plasma levels of thromboxane B2 (TxB2) were determined by radioimmunoassay in 6 consecutive patients with Prinzmetal's angina and in 9 healthy volunteers. In the normal group TxB2 was not detectable (= 0.5 pmoles/ml), while in patients with variant angina TxB2 was consistently detected (1.5-140 pmole/ml).

Topics: Adult; Angina Pectoris; Angina Pectoris, Variant; Animals; Female; Heparin; Humans; Male; Middle Aged; Rabbits; Radioimmunoassay; Thromboxane B2; Thromboxanes