thromboxane-b2 and Angina-Pectoris

Thromboxane has characteristics that signify potential importance in cardiovascular disease states. In models developed for studying thrombotic sudden death, thromboxane appears to be an important mediator. Thus, in arachidonic acid-induced sudden death, agents that either inhibit thromboxane generation or block thromboxane receptor activation prevent the occurrence of thrombotic death. Thromboxane mimetics are also useful in modeling sudden death; when injected i.v., these compounds elicit effects similar to those obtained with arachidonic acid. In this case, however, pretreatment with cyclooxygenase or thromboxane synthetase inhibitors confers no protection, whereas the thromboxane receptor antagonist retains its efficacy. Other factors that affect susceptibility to experimental sudden death include gender, species, and endocrine status. Thrombotic sudden death models have now been used to test, in vivo, the in vitro antiplatelet aggregatory effect of calcium-channel blockers. The data suggest that dihydropyridine agents such as nifedipine and nisoldipine are protective against thrombosis, whereas verapamil may have little such activity. Furthermore, sudden death induced by a variety of thrombotic challenges is prevented by pretreatment with nifedipine. The thrombotic sudden death models currently employed are useful for the in vivo study of the thrombotic process and for the evaluation of agents with potentially thrombotic or antithrombotic properties.

Topics: Angina Pectoris; Animals; Arachidonic Acid; Arachidonic Acids; Calcium Channel Blockers; Castration; Death; Estrogens; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Glucocorticoids; Humans; Male; Methacrylates; Prostaglandin Endoperoxides, Synthetic; Sex Factors; Testosterone; Thrombosis; Thromboxane A2; Thromboxane B2; Thromboxanes

To investigate the effects of supplementing qi and activating blood circulation method (YQHX) on platelet aggregation rate (PAgR), platelet adhesion rate (PAdR) and thromboxane B2(TXB2) level in patients with stable angina pectoris and intolerable to aspirin.. Seventy-six out-patients with stable angina (qi deficiency and blood stasis syndrom) pectoris intolerable to aspirin were randomized into two groups, 40 in the treated group and 36 in the control group. Both received conventional Western medicinal treatment with YQHX to the treated group additionally, for 1 month. PAgR, PAdR, TXB2 level, platelet count, hemoglobin concentration and fecal occult blood were measured before and 1 month after treatment, and the cardiac events as well as diges tive symptoms occurred in the observation period were recorded.. PAgR, PAdR and TXB2 level lowered in the treated group after 1-month treatment showed a significant difference to those of baseline, and also to those in the control group (all P <0.01). But no significant difference was found between pre-treatment and post-treatment, also between the two groups in platelet count, hemoglobin concentration, fecal figure and incidence of adverse cardiac events, as well as digestive symptoms (P > 0.05).. YQHX can effectively inhibit the platelet function in patients with stable angina pectoris without aggravation of digestive symptoms. Cardiac event reducing effect of YQHX was not seen in this study, it is necessary for large sampled study for confirmation.

Topics: Aged; Angina Pectoris; Aspirin; Blood Circulation; Cell Adhesion; Drug Tolerance; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Platelet Aggregation; Qi; Thromboxane B2; Treatment Outcome

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

1. A randomised double-blind placebo-controlled cross-over study was performed to investigate the effects of oral isosorbide dinitrate (ISDN; 20 mg twice daily for 2 weeks) on various aspects of platelet function in vivo in 20 patients with stable angina pectoris. Measurements were performed at rest and after platelet activation by physical exercise (bicycle ergometry). 2. Compared with placebo, treatment with ISDN significantly decreased systolic blood pressure at rest by 7 (-14 to -1) mm Hg (mean and 95% CI) and tended to increase exercise capacity by 7 (-1 to 14) W and attenuate perceived chest pain during maximal work. The dosage was high, as judged by side-effects reported (mainly headache). Compliance was good, as assessed by electronic counter equipped tablet bottles (Medication Event Monitoring System); only one patient had a compliance rate below 60%. 3. Exercise significantly increased platelet aggregability as measured by filtragometry ex vivo; the time taken for platelet aggregates in whole blood drawn directly from an antecubital vein to occlude a microfilter was significantly decreased from 155 to 95 s (antilog of mean log values). Platelet secretion in vivo also increased, as indicated by significant elevations of beta-thromboglobulin in plasma; from 22 to 35 ng ml-1 (P = 0.006). 4. ISDN treatment did not inhibit platelet function. Relative to placebo, filtragometry readings (ISDN/placebo ratios; mean and 95% CI) were not altered either at rest (1.05 (0.83 to 1.32)) or immediately after exercise (0.98 (0.80 to 1.20)). Similarly, beta TG in plasma was unaltered by ISDN treatment; 1.09 (0.98 to 1.21) at rest, and 1.04 (0.82 to 1.30) immediately after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Angina Pectoris; beta-Thromboglobulin; Blood Platelets; Creatinine; Cross-Over Studies; Double-Blind Method; Exercise Test; Hemodynamics; Humans; Isosorbide Dinitrate; Male; Middle Aged; Patient Compliance; Platelet Aggregation; Thromboxane B2

To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B2, 6-keto-prostaglandin F1 alpha, and leukotriene C4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B2 and leukotriene C4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Arachidonic Acids; Bepridil; Chronic Disease; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Rate; Humans; Leukotriene C4; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Radioimmunoassay; Single-Blind Method; Thromboxane B2

55 cases of Qi-deficiency and Blood-Stasis syndrome of coronary heart disease (CHD) and angina pectoris (AP) were divided randomly into two groups. Qi Xue granule (QXG) was administered to 30 cases of treated group, while compound Salvia tablet (CST) was administered to 25 cases of control group. Besides, both group were also given one placebo tablet or granule so as to eliminate the patient's psychological effects.. (1) Effects on clinical symptoms: Total effective rate for AP: 90% in QXG group, marked effective rate and effective rate for ischemic ECG changes were 30% and 46.6% respectively. All of these were better than that of CST group significantly (P < 0.05). Besides, QXG group could alleviate symptoms including asthenia. (2) Effects on submaximal paddle work load test: QXG group could prolong the capacity of exercise (from 336.2 +/- 34.7 to 437.5 +/- 43.8 seconds, P < 0.05), magnify the work load (from 73 +/- 7.18 to 94 +/- 8.5 W, P < 0.05) and elevate the ST segment (from 0.218 +/- 0.03 to 0.176 +/- 0.03 mV) significantly in comparison with CST group, which had little change only. (3) Effects on plasma TXB2, 6-keto-PGF1 alpha (6 Kp) level and ration of TXB2/6Kp in 10 normal subjects were 165 +/- 12.1 pg/ml, 142.6 +/- 17.4 pg/ml and 1.16 +/- 0.19 pg/ml respectively, while in 36 cases AP were 390.6 +/- 14.3, 106.0 +/- 7.9 and 3.67 +/- 0.85 pg/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Drugs, Chinese Herbal; Exercise Tolerance; Female; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Panax; Phytotherapy; Plants, Medicinal; Syndrome; Thromboxane B2; Yang Deficiency

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Bradykinin; Diltiazem; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Single-Blind Method; Thromboxane B2

The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double-blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Angina, Unstable; Blood Platelets; Double-Blind Method; Epoprostenol; Female; Fibrinopeptide A; Hemodynamics; Humans; Male; Middle Aged; Multicenter Studies as Topic; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Factor 4; Randomized Controlled Trials as Topic; Recurrence; Thromboxane B2

A dynamic thrombotic process, coronary spasm or both can be responsible for recurrent episodes of transient reduction of coronary blood flow in unstable angina. We have investigated the temporal relationship between episodic platelet activation, as detected by increased urinary excretion of 11-dehydro-TXB2, and spontaneous myocardial ischemia, assessed by continuous electrocardiographic monitoring and recording in 21 patients with unstable angina pectoris. In order to validate measurements of metabolite excretion as a reflection of intracoronary platelet activation, we have also performed repeated urine sampling from 8 patients undergoing PTCA and from 6 patients with peripheral vascular disease. The latter showed a 16% coefficient of variation in 3 consecutive 8-h urine samples. 11-dehydro-TXB2 increased significantly, by up to 15-fold, in the 2.5- to 5.0-h urine collection encompassing PTCA and decreased by greater than 50% during the following 2-h period. Patients with unstable angina were characterized by episodic increases (greater than 2 SD of controls) in metabolite excretion, in successive 6-8 h specimens. Paired measurements of 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 15 urine samples did not reveal evidence of altered metabolic disposition of endogenously released TXB2. A total of 125 ECG ischemic episodes were recorded, of which 64% asymptomatic. We have compared these biochemical and ECG changes in patients randomized to i.v. low-dose aspirin or i.v. isosorbide dinitrate and oral diltiazem. Twenty-five of 56 (i.e. 45%) urine samples obtained in aspirin-free periods showed increased metabolite excretion as compared to 15 of 88 (i.e. 17%) samples collected during aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Aspirin; Coronary Circulation; Drug Therapy, Combination; Electrocardiography; Humans; Isosorbide; Middle Aged; Platelet Activation; Radioimmunoassay; Thromboxane B2

Episodic platelet activation has been shown to occur in unstable angina, and aspirin should have an important therapeutic role in the management of these patients. The response to aspirin alone or to aspirin in combination with vasodilators such as heparin and beta-blockers has been assessed in 41 patients with unstable angina. Therapy was added sequentially in the event of recurrence of transient myocardial ischemia. Patients were randomly assigned to two groups. Group 1 (21 patients) received an intravenous infusion of isosorbide dinitrate and oral diltiazem, and group 2 (20 patients) received intravenous aspirin (60 mg the first day and 20 mg on successive days). This dose of aspirin reduced serum thromboxane B2 from 160 +/- 88 ng/ml (mean +/- SD) to undetectable values (less than 6 ng/ml, p less than 0.01). If episodes of ischemic ST segment shift continued, the therapy of group 1 was added to that of group 2 or vice versa; if further ST segment changes were documented, intravenous heparin and oral beta-blockers were added; if episodes of myocardial ischemia persisted, urgent coronary arteriography and myocardial revascularization were performed. Nine patients in group 1 and six in group 2 (p = 0.8) had no further episodes of myocardial ischemia on their initial therapy; 12 additional patients had no further episodes when taking combined therapy of aspirin and vasodilators. Thus, the administration of aspirin alone was not superior to coronary dilators; 30% of all patients continued to have episodes of myocardial ischemia or had a myocardial infarction develop when heparin and beta-blockers were added. Myocardial infarction occurred in one patient on vasodilator therapy alone, in two on combined therapy, and in two on full therapy. These results suggest that in some patients, the stimulus to coronary thrombosis and vasoconstriction occasionally becomes so strong that it cannot be inhibited by certain antagonist drugs. The unstable tendency to continuation of ischemia or evolution to myocardial infarction is not related to the severity of the persisting stenosis. Those patients not promptly responding to combined therapy immediately from admission should have early coronary angiography and aggressive treatment.

Topics: Angina Pectoris; Angina, Unstable; Aspirin; Diltiazem; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Humans; Isosorbide Dinitrate; Male; Middle Aged; Platelet Aggregation; Randomized Controlled Trials as Topic; Thromboxane A2; Thromboxane B2

The effect of a chemically stable prostacyclin analogue (Iloprost) on platelet function was investigated in a controlled study in patients with angiographically confirmed stable angina pectoris after ischaemic exercise. In placebo experiments, ADP platelet aggregation was increased after exercise only when measured in whole blood and not in PRP. While plasma thromboxane B2 levels were unchanged, those of 6-keto PGF1 alpha were significantly although transiently increased after exercise. Iloprost displayed a potent antiaggregating activity in PRP and also reversed platelet hyperaggregation occurring in whole blood determinations after exercise. Plasma thromboxane B2 levels were significantly reduced but occasionally a rebound increase occurred 30 min. after end of the infusion. In contrast plasma level of 6-keto PGF1 alpha did not change after Iloprost and its recorded post-exercise increase was counteracted, thus suggesting a negative feed-back mechanism between Iloprost and natural prostacyclin. The data also suggest that degradation of the analogue is probably accomplished through pathways different from those of PGI2.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Blood Platelets; Cardiovascular Agents; Coronary Disease; Epoprostenol; Humans; Iloprost; Male; Middle Aged; Physical Exertion; Platelet Aggregation; Platelet Function Tests; Random Allocation; Thromboxane B2

We have studied the antiaggregatory effect of fenflumizole, a new non-steroidal antiinflammatory imidazole derivative, in ten patients with unstable angina pectoris. We have measured the aggregation induced by arachidonic acid (AA), ADP, and collagen, and serum or plasma concentrations of beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), thromboxane B2 (TXB2), and fenflumizole before, during, and after treatment with fenflumizole in two different regimens either as 10 mg b.i.d. for four days followed by 10 mg daily for six days (Group I, n = 5), or as 20 mg b.i.d. for four days followed by 20 mg daily for six days (Group II, n = 5). The threshold concentration of AA-induced platelet aggregation increased in both groups by the first day of treatment, the mean increase being significantly higher in Group II than in Group I. There was close correlation between serum fenflumizole and the threshold concentration of AA-induced platelet aggregation (r = 0.95). A significant fall in TXB2 occurred in both groups. In group I TXB2 concentrations subsequently increased to initial values during treatment, whereas it remained significantly reduced in Group II. There were no significant changes in collagen and ADP aggregation, and beta-TG and PF-4 concentrations remained unchanged during and after the administration of fenflumizole.

Topics: Adenosine Diphosphate; Adult; Aged; Angina Pectoris; Angina, Unstable; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; beta-Thromboglobulin; Clinical Trials as Topic; Collagen; Female; Humans; Imidazoles; Male; Middle Aged; Platelet Aggregation; Platelet Factor 4; Thromboxane B2; Verapamil

To determine if the calcium antagonist nicardipine protects the myocardium against ischemia, myocardial lactate, hypoxanthine and prostanoid function was studied in 12 patients during percutaneous transluminal coronary angioplasty (PTCA). Values were obtained before balloon inflation and during 4 minutes after deflation. Intracoronary injection of 0.2 mg of nicardipine distal to the stenosis was done randomly before the first or second inflation; the other inflation served as a control. One minute after deflation, coronary sinus flow levels were similar during the nicardipine and control procedure (161 +/- 61 vs 159 +/- 72 ml/min); lactate (-9 +/- 21% vs -17 +/- 21%, p less than 0.025) and hypoxanthine production (-107 +/- 85% vs -218 +/- 153%, p less than 0.05) were less severe after nicardipine pretreatment than after control. All patients reverted to lactate extraction 4 minutes after inflation plus nicardipine infusion, whereas lactate was still produced 4 minutes after control inflation. No significant changes in thromboxane B2 or prostacyclin levels were observed in the coronary sinus 1 minute after inflation, but higher arterial thromboxane B2 values were observed after control inflation than after inflation with nicardipine infusion (median values 169 vs 78 pg/ml, p less than 0.05). In conclusion, intracoronary infusion of nicardipine reduced signs of ischemia and alterations in prostanoid handling after coronary occlusion. The mechanisms of myocardial protection appeared unrelated to coronary sinus blood flow changes or to a systemic effect of nicardipine.

Topics: Angina Pectoris; Angioplasty, Balloon; Coronary Disease; Coronary Vessels; Epoprostenol; Humans; Hypoxanthine; Hypoxanthines; Injections, Intra-Arterial; Lactates; Myocardium; Nicardipine; Oxygen Consumption; Thromboxane B2

Recently the possibility that nitrates inhibit platelet function in man has been explored in vitro and in vivo. We have studied the effect of isosorbide-5-mononitrate (ISMN), a stable and long-acting organic nitrate, on platelet function in vivo. Given orally within the current therapeutic range, the drug has practically no effect on platelet aggregation nor thromboxane generation in platelet-rich plasma in response to ADP, collagen, arachidonate, epinephrine and PAF. Synergistic effects of prostacyclin and ISMN on inhibition of ADP-induced platelet aggregation have been observed. Thus, local inhibition of platelet aggregation might not have been detectable, due to the short half-life in vitro of prostacyclin.

Topics: Adult; Angina Pectoris; Blood Platelets; Epoprostenol; Female; Humans; In Vitro Techniques; Isosorbide Dinitrate; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

1 We have performed a double-blind, randomized, 7-d cross-over study of the thromboxane synthetase inhibitor dazoxiben (UK 37248) in 20 patients with stable coronary heart disease. 2 All patients had a history of exertional angina of greater than two years duration and no patient had suffered a myocardial infarction in the preceding twelve months. 3 All patients had a positive exercise stress test for myocardial ischaemia and 15 had undergone coronary angiography. All these patients had a 50% narrowing in at least one vessel. 4 All patients were on conventional anti-anginal medication and the doses of their various therapies remained unchanged in the three months prior to and during the study period. 5 Therapy with dazoxiben 200 mg four times daily produced no alteration in the subjective or objective features of angina in these patients. There was no alteration in angina attack rate, glyceryl trinitrate consumption or duration of treadmill exercise. 6 Dazoxiben produced a highly significant reduction in both the resting and the post-exercise levels of serum thromboxane B2 levels, although there was no significant difference between the pre-exercise and post-exercise values. 7 Dazoxiben is an effective inhibitor of the synthesis of thromboxane but it has no effect on the subjective or objective features of stable coronary disease. This would suggest that the production of thromboxane and the development of circulating platelet aggregates play no part in the mechanism of angina in patients with stable coronary heart disease.

Topics: Angina Pectoris; Coronary Disease; Double-Blind Method; Humans; Imidazoles; Nitroglycerin; Oxidoreductases; Physical Exertion; Platelet Aggregation; Thrombelastography; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

Lysosomal membrane instability and platelet activation are both associated with acute myocardial ischemia. The effect of ibuprofen on cathepsin D as a marker of lysosomal membrane "leakiness" and thromboxane B2 as a marker of platelet activation was evaluated in 44 patients with angina pectoris. Samples of blood analyzed for cathepsin D, thromboxane B2, and lactate were withdrawn from the coronary sinus and brachial artery before and after pacing to 140 beats/min for 4 minutes. Myocardial ischemia was assessed by determination of transmyocardial lactate extraction or production. Ibuprofen (800 mg) or placebo was administered orally 2 hours before cardiac catheterization. Patients were classified into 4 groups on the basis of administration of placebo or ibuprofen and the presence or absence of myocardial ischemia as determined by demonstration of lactate extraction or production after atrial pacing. In patients with lactate extraction, no significant efflux of cathepsin D or thromboxane B2 occurred after pacing. In patients with lactate production given placebo, a 64 +/- 25% increase in the thromboxane B2 level and a 113 +/- 37% increase in cathepsin D activities occurred in the coronary sinus effluent sampled after pacing. In contrast, in patients with comparable coronary artery disease and comparable lactate production who were given ibuprofen, no release of thromboxane B2 (p = 0.05 compared with patients given placebo) or cathepsin D (p less than 0.01 compared with patients given placebo) occurred after pacing-induced ischemia. These findings suggest that ibuprofen stabilizes membranes and prevents platelet-activated release of thromboxane A2 in pacing-induced myocardial ischemia.

Topics: Angina Pectoris; Cardiac Pacing, Artificial; Cathepsin D; Cathepsins; Female; Humans; Ibuprofen; Lactates; Male; Middle Aged; Thromboxane B2

In 19 patients with unstable angina pectoris at rest, plasma levels of the platelet-derived proteins beta-thromboglobulin and platelet factor 4 were significantly elevated in blood samples obtained during or within 4 hours after episodes of angina, but were usually normal during quiescent intervals. Plasma levels of the arachidonic acid metabolite thromboxane B2 were less clearly related to angina, and there was no association of angina with levels of the coagulation product fibrinopeptide A. This demonstration of an association of platelet activation and secretion with unstable angina pectoris by radioimmunoassay of circulating platelet constituents offers a new approach to assessment of therapy in ischemic heart disease and suggests that agents that alter platelet function should be evaluated in patients with unstable angina.

Topics: Adult; Aged; Angina Pectoris; beta-Thromboglobulin; Blood Platelets; Electrocardiography; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Factor 4; Thromboembolism; Thromboxane B2

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

Markers of platelet activation are elevated in coronary artery disease. We sought to identify the presence and the potential associations of different markers of platelet activation.. We studied patients with unstable angina (n=28), patients with stable angina (n=36) and patients without coronary artery disease (n=30); sex and age matched. Blood levels of the adhesion molecule P-selectin, Thromboxane B2 and Serotonin were measured by enzyme immunoassays.. When we compared the groups the results were: sP-selectin, thromboxane B2 and serotonin levels were significantly higher in patients with unstable angina than in patients with stable angina.. These markers of platelet activation were able to identify unstable forms of coronary artery disease.

Topics: Angina Pectoris; Biomarkers; Coronary Artery Disease; Female; Humans; Male; Middle Aged; P-Selectin; Platelet Activation; Serotonin; Thromboxane B2

Topics: Angina Pectoris; Biomarkers; Cardiovascular Diseases; Electroencephalography; Heart Failure; Humans; Myocardial Infarction; Thromboxane B2; Time Factors

The effects of oral atenolol on coronary hemodynamics and prostaglandin metabolism have been investigated in 8 chronic stable angina pectoris patients who underwent the supine bicycle ergometer. At rest, atenolol taken orally reduced the pressure-rate product significantly (P < 0.05) but did not significantly affect the coronary sinus blood flow or the coronary sinus pressure. During exercise, atenolol also reduced the pressure-rate product significantly (P < 0.05) but did not significantly affect the coronary sinus blood flow, the coronary sinus pressure, or the coronary vascular resistance. Atenolol also did not significantly affect the thromboxane B2/6-keto prostaglandin F1 alpha ratio in the arterial blood before and after exercise but did reduce this ratio in the coronary sinus blood by 15% from 1.9 +/- 1.1 to 1.5 +/- 0.46 (P < 0.10) after exercise. These results indicate that atenolol taken orally does not significantly depress the coronary hemodynamics. However, the effects of atenolol on the prostaglandin metabolism could not be clearly determined.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Adult; Aged; Angina Pectoris; Atenolol; Blood Pressure; Exercise Test; Heart; Heart Rate; Hemodynamics; Humans; Lactates; Male; Middle Aged; Prostaglandins; Regional Blood Flow; Thromboxane B2; Vascular Resistance

The paper shows the high therapeutical efficiency of combined He-Ne laser therapy in patients with coronary heart disease. Its effect on the thromboxane-prostacyclin system is one of the mechanisms of laser impact. The combined He-Ne laser therapy promotes normalization of the level of thromboxane B2 and its ratio to the metabolite prostacyclin.

Topics: Adult; Aged; Angina Pectoris; Epoprostenol; Humans; Laser Therapy; Middle Aged; Prostaglandins; Thromboxane B2; Thromboxanes; Time Factors

Excretion of 2,3-dinor-thromboxane B2 released from activated platelets has been found elevated in patients with acute myocardial infarction and unstable angina. To investigate the role of thrombotic activity in postinfarction angina we measured urinary concentrations of 2,3-dinorthromboxane B2 in 20 patients over 10 days after myocardial infarction. Compared with 11 patients recovering pain-free, excretion of 2,3-dinorthromboxane B2 was found elevated in 9 patients who developed postinfarction angina. Accordingly, early postinfarction angina appears to be associated with ongoing thrombotic activity.

Topics: Aged; Angina Pectoris; Blood Platelets; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Thromboxane B2; Time Factors

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Humans; Myocardial Ischemia; Platelet Activating Factor; Thromboxane B2

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Bradykinin; Coronary Vessels; Female; Humans; Male; Myocardial Ischemia; Nociceptors; Pain Measurement; Thromboxane B2

We tested whether alteration of platelet sensitivity to prostacyclin (PGI2) is involved in the activation of platelets induced by exercise in patients with stable angina. Twenty patients and 20 control subjects underwent treadmill testing. Blood samples were obtained before and immediately after exercise for plasma thromboxane B2 (TXB2) and 6-keto-PGF1 alpha (6kP) assays and platelet aggregation studies. Dose-response curves for platelet aggregation to collagen were obtained in the presence and absence of 1 nmol/L PGI2 to quantify the antiaggregation effects of PGI2. At rest, platelet aggregation by collagen was enhanced in the patients. However, platelets were more sensitive to exogenous PGI2, apparently associated with lower plasma 6kP levels in the patients. After exercise, plasma TXB2 levels increased in the patients but not in the control subjects. Plasma 6kP levels remained unchanged and platelet sensitivity to PGI2 decreased in the patients whereas these values increased in the control subjects. The exercise-induced changes in platelet sensitivity to PGI2 correlated with those of platelet adenylate cyclase activity in response to 1 nmol/L PGI2 (r = 0.787, p less than 0.01). Thus impaired sensitivity of platelets to PGI2, in addition to the reduced response of prostanoid secretion, might be relevant to the platelet activation associated with exercise in patients with stable angina.

Topics: 6-Ketoprostaglandin F1 alpha; Adenylyl Cyclases; Angina Pectoris; Blood Platelets; Epoprostenol; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

Monocytic production of peripheral blood thromboxane B2 and leukotriene B4, levels of cAMP and total lipids in these cells were examined in 58 patients with stable angina induced by exercise and 32 healthy donors. There was a hyperproduction of thromboxane B2 and leukotriene B4 by monocytes in the patients, a decrease in cAMP levels, and lipid accumulation in these cells in effort angina. The calcium antagonists verapamil and nifedipine abolished the above impairments. The author suggests that calcium antagonists should be regarded as a new class of antiathero-sclerotic agents that have effects predominantly on the cellular link of atherogenesis.

Topics: Angina Pectoris; Calcium Channel Blockers; Coronary Disease; Cyclic AMP; Humans; In Vitro Techniques; Leukotriene B4; Lipids; Monocytes; Nifedipine; Thromboxane B2; Verapamil

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 evaluate in vivo platelet activation, 11-dehydro-thromboxane B2 levels in plasma and urine were measured in 9 patients with unstable angina and 11 with stable angina using radioimmunoassay modified by the extraction method of Kawano et al. The 2 groups were matched for age, sex, coronary risk factors, medications or atherosclerotic lesions in coronary angiography. Although there was no difference in the plasma level between the 2 groups in the usual state, urinary 11-dehydro-thromboxane B2 amount in unstable angina was significantly increased compared to the stable angina group (865.5 +/- 238.7 vs 535.9 +/- 177.4 pg/mg creatinine (mean +/- SD), p < 0.01). There was no correlation between the 11-dehydro-thromboxane B2 level and the degree of coronary atherosclerosis in either group. The plasma level increased during the attacks in 2 patients with unstable angina. The amount of urinary 6-keto-PGF1 alpha did not differ between the 2 groups. These findings suggest that platelet activation in vivo is more pronounced in unstable angina than in stable angina, and that the measurement of urinary 11-dehydro-thromboxane B2 may be useful for evaluating and treating angina.

Topics: Angina Pectoris; Angina, Unstable; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Radioimmunoassay; Thromboxane B2

The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production.. We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11-dehydrothromboxane B2 was measured in patients with stable angina after exercise-induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma.. Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiac Pacing, Artificial; Complement Activation; Complement C5a; Coronary Disease; Electrocardiography; Female; Humans; Lactates; Lactic Acid; Male; Middle Aged; Myocardium; Thromboxane B2

Platelet behavior was compared in two groups of patients with unstable angina: 13 patients with rest pain and ST depression on the electrocardiogram (the intermediate coronary syndrome), 14 patients with progressive angina without rest pain, and 20 healthy controls. Both patient groups had hyperaggregating platelets when compared with the controls (p less than 0.01). Platelet aggregation was measured ex vivo in the presence of arachidonic acid. Serum thromboxane B2, plasma beta-thromboglobulin, and platelet factor 4 were all temporarily increased in the group with intermediate coronary syndrome (p less than 0.01), whereas measurements in patients with progressive angina were not significantly different from the controls. Thus, patients with the intermediate coronary syndrome, who have a high frequency of suboccluding coronary artery thrombus and a very serious prognosis, had severely altered platelet behavior in contrast to patients with progressive angina.

Topics: Angina Pectoris; Angina, Unstable; beta-Thromboglobulin; Coronary Thrombosis; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Factor 4; Prognosis; Thromboxane B2

Examination of the effect of calcium antagonists on the functional activity of monocytes revealed the possibility of using these cells as an object for testing antiatherosclerotic agents. The functional activity of monocytes was evaluated by their capacity of producing thromboxane B2 and by the cellular content of cyclic AMP. It is suggested that calcium antagonists verapamil and niphedipin, in particular, are potential antiatherosclerotic agents.

Topics: Angina Pectoris; Arteriosclerosis; Calcium Channel Blockers; Cells, Cultured; Cyclic AMP; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Monocytes; Physical Exertion; Thromboxane B2

24 angina pectoris patients were treated with Codonopsis pilosulae (CP) oral solution 20 ml (containing crude CP 20 g) thrice daily for 7 days, other 10 cases were treated by aspirin 0.5 g per day for a week as the control group. After treatment, in the CP group, the plasma level of TXB2 was obviously reduced from 156.76 +/- 11.87 pg/ml to 125.01 +/- 8.85 pg/ml (means +/- S means), the inhibitory rates was 15. 67% (P less than 0.05), and of 6-keto-PGF1 alpha (6-K) was not markedly changed (P greater than 0.05). In the aspirin group, TXB2 was also reduced significantly (P less than 0.05); 6-K was reduced more than that of CP group, the inhibitory rate was 24.33 +/- 9.40% (P less than 0.05). To reveal the mechanism of CP action on the synthesis of TXA2 and PGI2, the porcine lung microsome was used as the donor of cyclooxygenase, thromboxane synthase and prostacyclin synthase, the effects of CP on the formation of TXB2 and 6-K from arachidonic acid (AA) or endoperoxides were measured by RIA respectively. The results showed that both the levels of the formation of TXB2 from AA or endoperoxides were markedly reduced by CP in a dose-dependent (at doses of 3-300 mg/ml). The synthesis of TXB2 was distinctly inhibited alone with a dose of 100 mg/ml CP, which suggested that CP might be an inhibitor of TXB2 synthase at that dose; while at a dose of 300 mg/ml CP, the synthesis of TXB2 and 6-K were inhibited simultaneously (P less than 0.001). It showed that a larger dosage of CP, which could inhibited the synthesis of both TXA2 and PGI2, its mechanism of action needs further study.

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris; Animals; Drugs, Chinese Herbal; Epoprostenol; Female; Humans; Male; Microsomes; Swine; Thromboxane B2

Topics: Angina Pectoris; Cardiac Pacing, Artificial; Coronary Angiography; Coronary Disease; Electrocardiography; Female; Humans; Middle Aged; Thromboxane B2

Topics: Angina Pectoris; Arachidonic Acids; Chromatography, High Pressure Liquid; Humans; Myocardial Infarction; Radioimmunoassay; Reference Values; Thrombosis; Thromboxane B2

Plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandin Fl alpha(6-K-PGFl alpha), the stable nonenzymatic metabolites of TXA2 and prostacyclin were assayed in 30 patients suffering from angina pectoris before and after administration of puerarin. In addition, serum lipids and HDL were also measured at the same time. 20 healthy subjects were chosen as the control group. Two weeks before and during administration of puerarin, aspirin, calcium-antagonists, all kinds of hypotensors and drugs relieving chest pain of angina pectoris were strictly prohibited. Puerarin was intravenously given, 500 mg daily for 7 days, which was considered as a therapeutic course. Besides relieving of chest pain, decreasing of heart rate and reduction of blood pressure clinically, it was also found that plasma 6-K-PGFl alpha concentrations were significantly elevated from 38.32 +/- 15.40 to 158. 79 +/- 98.62 pg (P less than 0.01) after administration of puerarin, but there was no significantly difference between plasma TXB2 concentrations before and after administering the drug. In addition, serum HDL was apparently enhanced as compared with that before the administration of puerarin (P less than 0.01). The results indicated that puerarin has the function of anti-angina, reducing both systolic and diastolic blood pressure and diminishing myocardial oxygen consumption.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angina Pectoris; Female; Flavonoids; Humans; Isoflavones; Male; Oxygen Consumption; Radioimmunoassay; Thromboxane B2; Vasodilator Agents

Platelet aggregation (PA), platelet thromboxane B2 (TXB2) generation and 14C 5-hydroxytryptamine (5HT) release were studied in 13 patients with unstable angina, and compared to 14 patients with stable angina and 16 healthy controls. A typical pattern, distinct in 4 aspects from stable angina patients or controls, was observed in the unstable angina patients. ADP or collagen induced shape change was 3-4 times greater, the extent of epinephrine induced PA was nil or very low, the extent of collagen induced 14C 5HT release was also reduced while collagen induced platelet TXB2 generation was increased in spite of a reduced extent of PA. The extent of ADP or collagen induced PA was also significantly reduced. These results indicate a platelet membrane abnormality occurring presumably during contact of the circulating platelets with a non-occlusive thrombus observed at sites of ruptured plaques in unstable angina patients. Since also the pattern (20-30% overlap with control values) was distinct from that of stable angina patients, it might indicate an active thrombotic process. Plasma beta-thromboglobulin (beta TG) and TXB2 levels and serum TXB2 generation were also studied in the cardiac patients and controls and in another 10 patients with advanced peripheral occlusive arterial disease (POAD). Plasma beta TG and TXB2 levels were slightly elevated in the unstable angina patients and markedly elevated in the POAD patients. Serum TXB2 generation was, however, elevated in the stable angina patients (p less than 0.002) and more so in the unstable angina patients (p less than 0.001) compared to controls or to POAD patients. This was presumably mediated through enhanced thrombin generation. These results suggest that the measured plasma beta TG variable in the unstable angina patients is not useful in the assessment of in vivo platelet activation. It is presumably reflecting the sum of local enhanced platelet activation (at sites of ruptured plaques) and of reduced function of the "defective" circulating platelets. The ability of the platelets of unstable angina patients to generate large amounts of TXB2 if occurring in vivo might induce an intense coronary vasospasm.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Arterial Occlusive Diseases; beta-Thromboglobulin; Blood Platelets; Humans; Middle Aged; Platelet Aggregation; Serotonin; Thromboxane B2

To investigate the pathophysiology of intracoronary thrombus formation we measured whole blood aggregation in response to ADP, platelet activating factor (PAF) and collagen, along with thromboxane B2 (TXB2) production during collagen induced aggregation, plasma TXB2 and plasma levels of lyso-PAF, in 38 subjects with and without ischaemic heart disease (12 with acute myocardial infarction, 9 with prolonged ischaemic chest pain without infarction and 17 normals). Lyso-PAF was measured, after in vitro acetylation to active PAF, by bioassay using 14C-serotonin labelled rabbit platelets. TXB2 was measured by radioimmunoassay. Plasma TXB2 was elevated at presentation only in patients with myocardial infarction (p less than 0.01). While impedance aggregation was similar in the three groups, aggregation to collagen resulted in greater release of TXB2 in subjects with myocardial infarction (p less than 0.01), an abnormality persisting 2-4 months later. Plasma lyso-PAF levels were significantly depressed throughout the first week in subjects with infarction (p less than 0.002), but after 2 to 4 months the level was greater than in normal subjects (p less than 0.001), changes presently unexplained. It is possible that the disorder of platelet function preceded and predisposed to coronary thrombosis. The findings strengthen the grounds for aspirin therapy in acute myocardial infarction.

Topics: Adenosine Diphosphate; Aged; Angina Pectoris; Angina, Unstable; Collagen; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activating Factor; Platelet Aggregation; Thromboxane B2

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Bradykinin; Coronary Disease; Electrocardiography, Ambulatory; Exercise Test; Humans; Male; Middle Aged; Thromboxane B2

The changes of platelet functions including platelet membrane microviscosity (PMMV), plasma 5-HT, plasma TXB2 and 6-K-PGF1a were studied in 30 cases of AMI and 13 cases of unstable angina (UA), 20 normal subjects as control. After onset of AMI, PMMV, plasma 5-HT, 6-k-PGF1a all increased quickly, especially on the 1st day (P less than 0.001-0.01). During 3 weeks observation, only 6-K-PGF1a decreased to the normal level on 14th day. There were no obvious decrease of plasma TXB2, 5-HT and PMMV. It showed that in acute phase of AMI without intervention of any antiplatelet drugs the platelets were activated continuously. Plasma 5-HT was the most sensitive predictor for the severity of AMI as observed by the comparison between the cases with complications and serum peak CK greater than 1000 U/L, and those without complications and peak CK less than 1000 U/L (P less than 0.001-0.05). The great change of PMMV was a bad prognosis. In patients with UA, during acute myocardial ischemia, the platelets were also activated significantly, but the extent was not as high as that in AMI.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Blood Platelets; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Function Tests; Serotonin; Thromboxane B2

Platelet function (aggregation, circulating platelet aggregates, platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-PGF1 alpha, platelet count) was evaluated in patients with angina of new onset, as compared to individuals without coronary heart disease, and patients with angina of long standing (28 +/- 4.6 months). Some of the patients with angina of new onset were examined repeatedly 6 to 12 months after the onset of angina. Platelet activity was shown to be significantly higher in patients with stable angina of new onset, as compared to patients with lasting angina, where ADP and serotonin were used as inductors. Platelet aggregation, induced by platelet activation factor and collagen, was similar in all groups. Repeated investigation 6 to 12 months after the first anginal attacks demonstrated that most of platelet functional parameters declined or tended to decline.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angina Pectoris; Angina, Unstable; beta-Thromboglobulin; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Factor 4; Thromboxane B2; Time Factors

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Angina Pectoris; Animals; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Pre-Eclampsia; Pregnancy; Rabbits; Radioimmunoassay; Rats; Rats, Inbred Strains; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Humans; Male; Middle Aged; Physical Exertion; Thromboxane B2

Fibrinopeptide A, platelet factor 4, beta-thromboglobulin, thromboxane B2, and 6-keto-prostaglandin F1 alpha were estimated by radioimmunoassay on venous plasma samples taken within 48 hr of admission from 16 consecutive patients with unstable angina and 15 patients with stable angina matched for clinical variables. The ratio of circulating platelet aggregates, platelet aggregation to increasing concentrations of ADP (0.455 to 1.82 micrograms/ml), and platelet thromboxane B2 production in vitro were also tested. The two groups of patients were statistically similar in terms of sex distribution, age, presence of risk factors, use of medication, extent of coronary artery disease and history of previous myocardial infarction. Mean plasma levels of fibrinopeptide A were 2.7 +/- 0.4 ng/ml (geometric means +/- SEM, range 1.5 to 5.5) in patients with stable angina vs 5.5 +/- 1.8 ng/ml (range 2.4 to 32; p less than .001) in those with unstable angina. In the latter group, after 6 to 8 days, fibrinopeptide A levels decreased to 3.6 +/- 0.5 ng/ml (range 1.5 to 9.3; p less than .04 vs admission). All other variables measured were statistically identical in the two groups. We conclude that plasma fibrinopeptide A levels, as opposed to platelet factors, discriminate between patients with unstable and stable angina, indicating an activation of the coagulation system in unstable angina.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Angina Pectoris; Angina, Unstable; beta-Thromboglobulin; Coronary Angiography; Fibrinogen; Fibrinopeptide A; Heart Ventricles; Humans; Physical Exertion; Platelet Aggregation; Platelet Factor 4; Thromboxane B2; Time Factors

We studied the levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), platelet aggregability, beta-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB2 levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF1 alpha levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6 min (p less than 0.001). Plasma TXB2 level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise. These results suggest that a marked increase in TXA2, with only a minimal change in PGI2, during exercise may contribute to exercise-induced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Angina Pectoris; Coronary Disease; Epoprostenol; Female; Humans; Male; Methacrylates; Physical Exertion; Platelet Aggregation; Thromboxane B2; Thromboxane-A Synthase; Vasoconstriction

Thromboxane released from activated platelets and prostacyclin of the vessel wall may act as potent antagonistic modulators of platelet aggregability and coronary vascular tone. Therefore, urinary excretion of their major metabolites, 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 alpha, was studied in 16 patients presenting with prolonged angina at rest. The 10 patients whose condition did not improve under vigorous antianginal treatment within 48 hours exhibited higher thromboxane metabolite excretion than did the 6 patients who responded to therapy (2,208 +/- 1,542 versus 609 +/- 312 ng/g creatinine; p less than 0.001). Elevated values were also found in four of eight patients with sustained postinfarction angina. Enhanced thromboxane metabolite excretion was frequently associated with angiographic evidence of thrombus formation. When nine patients were restudied in a stable phase after 11 +/- 5 months, thromboxane metabolite excretion was consistently normal or high normal. Excretion of prostacyclin metabolites was not depressed in any patient but correlated weakly with thromboxane (r = 0.41). Thus, enhanced thromboxane production as an index of platelet activation may identify patients with active thrombus formation who could benefit most from platelet inhibitory treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina Pectoris; Angina, Unstable; Electrocardiography; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Monitoring, Physiologic; Platelet Aggregation; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris; Drugs, Chinese Herbal; Female; Humans; Male; Thromboxane B2

Platelet function was studied in patients with diverse clinical patterns of unstable angina. In vasospastic angina, anginal attacks coincide with the highest increment in Ca2+ of platelets, and their high sensitivity to aggregation inductors, which declines as the condition stabilizes. Unstable angina without the vasospastic component is associated with reduced platelet sensitivity to aggregation inductors, particularly so in patients showing signs of intracoronary thrombosis. Spontaneous anginal attacks are accompanied with a rise of thromboxane B2 and a drop in the stable prostacyclin metabolite level.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angina Pectoris; Angina, Unstable; Blood Platelets; Calcium; Cytoplasm; Female; Humans; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris; Angina, Unstable; Blood Platelets; Epoprostenol; Humans; Myocardial Infarction; Thromboxane A2; Thromboxane B2

The levels of TxB2 and 6-keto-PGI alpha in the coronary sinus and thoracic aorta blood were determined in 14 patients with angina pectoris and signs of coronary atherosclerosis. 12 patients were involved in a dynamic study: before, during and 10 minutes after ischaemia-inducing atrial pacing. In all the patients atrial pacing resulted in a typical episode of angina, in 7 of them ST-segment depression of not less than 2 mm was seen on the ECG. In one patient arachidonic acid metabolites were evaluated during the control period and during a spontaneous episode of angina accompanied by ST-segment elevations. In 8 of 9 patients TxB2 was produced by the myocardium during atrial pacing. During monitored evaluation of arachidonic acid metabolites one patient with spontaneous angina demonstrated a gradual lowering of the 6-keto-PGI alpha, it being minimal by the beginning of the episode; TxB2 level increased more rapidly.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angina Pectoris; Coronary Disease; Electric Stimulation; Heart Atria; Humans; Male; Middle Aged; Thromboxane B2

Immunoreactive thromboxane B2 (i-TXB2) was measured by radio-immunoassay (RIA) in urines collected over eight hours on the day of admission in 25 patients who were admitted with the diagnosis of myocardial infarction. In 16 of the patients myocardial infarction was confirmed by ECG and plasma enzymes. Another patient presented with pulmonary embolism and the remaining eight patients had angina pectoris. A further eight hour urine collection was obtained 24 hours later from eleven of the sixteen patients with myocardial infarction. In these eleven patients myocardial infarction was associated with five fold higher urine i-TXB2 (2.72 +/- 0.48 ng/ml) at the day of admission when compared to patients admitted under the same diagnosis but found to have angina only (0.51 +/- 0.08 ng/ml, p less than 0.001). In patients with myocardial infarction the urine i-TXB2 values were reduced 24 hours later (1.58 +/- 0.27 ng/ml, p less than 0.01). One patient was followed with urine i-TXB2 from three days prior to diagnosis of myocardial infarction and to one day prior to a second infarction. In this patient i-TXB2 was highest three days prior to infarction. We conclude that this early elevation of urine i-TXB2 three days prior to diagnosis of infarction and the increased i-TXB2 in patients with myocardial infarction when compared to patients with angina suggest thromboxane is probably released from activated platelets prior to infarction. We suggest that urine i-TXB2 may be of value in the differential diagnosis between myocardial infarction and angina.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Coronary Disease; Coronary Thrombosis; Diagnosis, Differential; Humans; Middle Aged; Myocardial Infarction; Pulmonary Embolism; Radioimmunoassay; Thromboxane B2

Peripheral vascular resistance (PVR) and thromboxane A2(TxA2) synthesis after the cold pressor test were investigated in different subsets of patients with angina (10 with stable effort angina, 36 with resting angina [24 in an active phase and 12 in an inactive phase], and five with Prinzmetal's variant angina) and in 41 control subjects of equivalent age and risk factors. Left ventricular end-diastolic pressure, ejection fraction, extent of coronary angiographic lesions, and baseline PVR were not significantly different among the various patient groups. In all patient groups, except those with variant angina, the cold pressor test resulted in a higher increase in PVR than in the control subjects (p less than .001 for all groups). In patients with variant angina the vasoconstrictor response was increased only in proximity (about 1 hr) to ischemic attacks. In patients with active resting angina the vasoconstrictor response was on the average four times longer than that in patients with effort angina and with inactive resting angina (p less than .001). This exaggerated vasoconstrictor response was associated with elevated TxA2 resting levels in plasma and with increased TxA2 synthesis after the cold pressor test. A linear relationship was found between the area of the vascular response and the area of TxA2 production after the cold pressor test in patients with active resting angina (r = .87, p less than .001). The increased TxA2 synthesis and the inappropriate increase of peripheral vascular response to sympathetic stimulation revert back to normal in the inactive phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angina Pectoris; Blood Pressure; Cold Temperature; Humans; Physical Exertion; Regional Blood Flow; Sympathetic Nervous System; Thromboxane A2; Thromboxane B2; Vascular Resistance

Spontaneous increase in platelet activity and change in coronary vasomotor tone have been implicated in the pathogenesis of acute myocardial ischemia. To define the mechanism of platelet "hypersensitivity" in acute myocardial ischemia, we examined the status of platelet alpha 2-adrenergic receptors in patients hospitalized with severe unstable angina. With the use of the specific alpha 2-receptor antagonist 3H-yohimbine, we identified a 26% decrease in the receptor binding sites on platelet membranes from patients with unstable angina compared with controls (155 +/- 32 vs. 210 +/- 29 fmol/mg protein, P less than or equal to 0.005). The dissociation constants of 3H-yohimbine binding to platelet alpha 2-receptors were similar in both groups (3.3 +/- 1.1 and 4.1 +/- 1.6 nmol/L, P not significant). To study the alterations in the affinity of platelet alpha 2-receptors for the agonists, effects of 1-epinephrine on specific binding of 3H-yohimbine were examined. We observed a marked reduction in 1-epinephrine concentration for inhibition of antagonist binding by 50% in acute myocardial ischemia (IC50: 4.2 +/- 3.9 X 10(-8) vs. 6.7 +/- 3.4 X 10(-7) mol/L, P less than or equal to 0.01), indicating increase in platelet alpha 2-receptor affinity for the agonist. Platelet aggregation and thromboxane A2 generation in response to epinephrine were also significantly increased in the acute phase of myocardial ischemia. This study suggests enhanced affinity of platelet alpha 2-receptors to the agonist 1-epinephrine as a possible mechanism of platelet hypersensitivity in acute myocardial ischemia.

Topics: Acute Disease; Adrenergic alpha-Agonists; Aged; Angina Pectoris; Angina, Unstable; Blood Platelets; Catecholamines; Coronary Disease; Epinephrine; Humans; Male; Middle Aged; Platelet Aggregation; Receptors, Adrenergic, alpha; Thromboxane A2; Thromboxane B2; Yohimbine

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Angina Pectoris; Coronary Disease; Humans; Methacrylates; Oxidoreductases; Physical Exertion; Platelet Aggregation; Prostaglandins; Thromboxane B2; Thromboxane-A Synthase

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris; Coronary Disease; Dinoprostone; Humans; Myocardium; Prostaglandins; Prostaglandins E; 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

In order to diagnose patients in thrombotic state, it is quite important to detect increased concentration of plasma thromboxane B2 (TXB2), a stable catabolite of TXA2. To determine plasma TXB2 levels with high sensitivity and selectivity, we employed gas chromatography-mass spectrometry (GC/MS). The trimethylsilyl (TMS) ether derivatives conventionally employed in GC/MS analysis of prostanoids are not suitable for quantitation of plasma prostanoids, because the mass spectra are deficient in ions with high intensity in the high mass range and TMS ether derivatives are sensitive to moisture. To solve these problems we employed tert-butyldimethylsilyl (t-BDMS) ether derivatives, based on the observation that t-BDMS ether derivatives afforded abundant ions at [M-57]+ and showed good hydrolytic stability. The reaction conditions of tert-butyldimethylsilylation were also examined to optimize the selected ion monitoring response. The t-BDMS ether derivatives of prostanoids were successfully analyzed with a short capillary column with a relatively large diameter, with maintaining good separation. In conjunction with the use of reversed-phase high performance liquid chromatography as purification procedure, a sensitive and reproducible stable isotope dilution assay of plasma TXB2 was developed. The values obtained by this method correlated well with those obtained by the radioimmunoassay we have developed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Coronary Vasospasm; Dinoprost; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Myocardial Infarction; Organosilicon Compounds; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Silicon; Thromboxane B2; Thromboxanes

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Topics: Administration, Oral; Adult; Aged; Angina Pectoris; Aspirin; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Female; Hemodynamics; Humans; Lactates; Lactic Acid; Male; Middle Aged; Myocardial Infarction; Thromboxane B2; Vascular Resistance

Thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2), was measured in the coronary sinus and in aortic blood before and after cold pressor test (CPT) in 21 patients suffering from ischemic heart disease (7 affected by stable effort angina and 14 by unstable angina) and in 12 patients not suffering from myocardial ischemia (control group) during coronary angiography. Aspirin (10 mg/kg intravenously) was administered before catheterization in order to prevent platelet and leukocyte TXA2 formation. Control subjects and patients with effort angina had TXB2 resting levels lower than unstable angina patients without a transcardiac gradient which, on the contrary, was found in unstable angina patients. Only in these patients CPT resulted in a significant TXB2 increase more marked in the coronary sinus (from 50.0 +/- 18.9 pg/ml to 73.0 +/- 35.1 pg/ml, p less than 0.001) than in the aorta (from 33.4 +/- 17.1 pg/ml to 42.6 +/- 24.0 pg/ml, p less than 0.05), so that the transcardiac TXB2 gradient significantly increased. In all but two unstable angina patients, TXB2 elevation was not associated with a fall of cardiac lactate extraction. The resting and CPT-induced TXB2 gradients were unrelated to the presence and severity of coronary angiographic lesions. These results indicate that unstable angina patients show an abnormal cardiocoronary capacity to synthesize TXA2, which seems not to be elicited by the occurrence of myocardial ischemia.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Aorta; Cold Temperature; Coronary Angiography; Coronary Vessels; Female; Humans; Lactates; Male; Middle Aged; Sympathetic Nervous System; Thromboxane A2; Thromboxane B2; Thromboxanes

Patients with polycythemia vera have been described to have hemorrhagic as well as thrombotic tendencies. In a patient with polycythemia vera and angina pectoris, we observed markedly decreased platelet aggregation response to epinephrine but increased platelet and whole-blood thromboxane A2 generation compared with normal subjects. Electron microscopy mostly showed partially activated forms of platelets, which may account for decreased aggregation response in vitro and hemorrhagic tendencies. Young and large platelets found in this disease, however, can generate large amounts of vasoconstrictor and platelet proaggregatory prostanoid thromboxane A2 in response to endogenous thrombin, which may be a basis for thrombotic tendencies.

Topics: Angina Pectoris; Blood Platelets; Humans; Male; Microscopy, Electron; Middle Aged; Platelet Aggregation; Polycythemia Vera; Thromboxane A2; Thromboxane B2; Thromboxanes

14 patients with effort induced angina pectoris were treated with a specific TxB2 inhibitor Dazoxiben or verapamil for two weeks with a wash-out period of 14 days between the two regimens. A sub-maximal bicycle test was performed before treatment and at the end of each treatment period. The bicycle test induced a significant increase in serum TxB2 in patients without treatment and during verapamil therapy. This increase was significantly inhibited by Dazoxiben treatment. No alterations in plasma TxB2 or 6-keto-PGF1 alpha were observed on either regimen. Dazoxiben had no clinical effect, while verapamil caused a highly significant prolongation of exercise time.

Topics: Aged; Angina Pectoris; Exercise Test; Female; Humans; Imidazoles; Male; Middle Aged; Oxidoreductases; Prostaglandins; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes; Verapamil

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

The possibility that isosorbide dinitrate (ISDN) inhibits platelet function in humans has been explored in vitro and in vivo. Incubation of citrated platelet-rich plasma from healthy subjects with scalar concentrations (1.25, 12.5 and 125 micrograms/ml) of ISDN for 5 and 10 minutes resulted in a decrease in platelet aggregation after ADP, adrenaline, and arachidonic acid at the highest drug concentration (mean decrease: 72% [p less than 0.01], 56% [p less than 0.05] and 62% [p less than 0.05], respectively, with the 10-minute incubation). Also, a significant reduction (30%) in generated thromboxane (TX)B2 levels was observed after arachidonic acid (p less than 0.01). ISDN was then infused at rate of 4 mg/hour for 30 minutes in 11 patients with angina and at a rate of 30 mg/hour for 20 minutes in 8. The smaller dose, which caused minor changes in arterial pressure and heart rate, was accompanied by a marked, significant decrease in ADP- and adrenaline-induced aggregation, with a nadir at 60 minutes from the infusion stop (decreases of 40% and 51% respectively). Circulating platelet aggregates also decreased, with a minimum (-41%, p less than 0.05) at the end of the infusion. The higher infusion rate, causing marked hemodynamic effects, was not accompanied by the occurrence of clear antiplatelet effects. Thus, ISDN can affect platelet function both in vitro and in vivo. The in vivo effect occurs at lower concentrations than in vitro but is blunted when a marked hemodynamic response occurs.

Topics: Adenosine Diphosphate; Adult; Angina Pectoris; Arachidonic Acid; Arachidonic Acids; Blood Pressure; Epinephrine; Female; Heart Rate; Humans; In Vitro Techniques; Infusions, Parenteral; Isosorbide Dinitrate; Male; Middle Aged; Platelet Aggregation; Thromboxane B2

Topics: Acrylates; Adult; Angina Pectoris; Female; Humans; Male; Methacrylates; Middle Aged; Myocardial Infarction; Oxidoreductases; Physical Exertion; Platelet Aggregation; Reference Values; Thromboxane B2; Thromboxane-A Synthase

To determine thromboxane A2 release in coronary artery disease, we measured its stable metabolite thromboxane B2 by radioimmunoassay in 20 patients. In 15 patients with stable disease (last angina episode greater than 96 hours before study), coronary venous thromboxane B2 concentrations were lower than in aortic blood (mean 109 +/- 36 vs 194 +/- 40 pg/ml, p less than 0.001). In contrast, in five other patients with spontaneous angina, coronary venous thromboxane B2 concentrations were higher than aortic thromboxane B2 concentrations during the angina episode (mean 1716 +/- 316 vs 875 +/- 388 pg/ml, p less than 0.02). Plasma thromboxane B2 levels were in the normal range (mean 175 +/- 35 pg/ml) in patients with stable angina but significantly (p less than 0.02) higher in patients with spontaneous angina. With atrial pacing to the point of chest pain and/or ECG changes in patients with stable coronary artery disease, aortic thromboxane B2 concentrations increased in 10 of 13 patients (mean 283 +/- 70 pg/ml, p less than 0.02). Coronary venous thromboxane B2 concentrations increased in seven patients at peak pacing rates (mean 223 +/- 76 pg/ml) and in three other patients after termination of pacing. These data indicate that release of thromboxane A2 is much greater during spontaneous angina than with pacing stress in patients with coronary artery disease. Thromboxane A2 released during spontaneous or pacing-induced angina may modulate coronary and systemic vascular tone. Enhanced thromboxane A2 activity may either precede or follow myocardial ischemia and could be a factor in the initiation and propagation of the ischemic episode.

Topics: Adult; Aged; Angina Pectoris; Aorta; Cardiac Catheterization; Cardiac Pacing, Artificial; Coronary Disease; Coronary Vessels; Humans; Male; Middle Aged; Prostaglandins; Thromboxane A2; Thromboxane B2; Thromboxanes

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Epoprostenol; Humans; Middle Aged; Myocardial Infarction; Radioimmunoassay; Thromboxane A2; Thromboxane B2; Thromboxanes

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

Topics: Angina Pectoris; Cardiac Pacing, Artificial; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Coronary Disease; Hemodynamics; Humans; Myocardial Infarction; Prostaglandins; Risk; Thromboxane A2; Thromboxane B2

Platelet count, and plasma thromboxane B2 (TXB2) and circulating platelet aggregates (CPA) were determined in the coronary sinus (CS), aortic bulb (AO) and cubital vein (V) in 21 patients with stable angina and in 6 control subjects before and after atrial pacing (AP). TXB2 measurements were repeated before and after AP in 6 of the 21 angina patients after 15 days' sulphinpyrazone treatment. Platelet count and CPA ratio were similar in angina patients and controls at all three sampling sites and were unchanged at AP peak. In the controls, basal TXB2 values in CS, AO and V were not significantly different and were unchanged at AP peak. In the angina patients compared with the controls, basal TXB2 values in the AO, CS and V were not significantly different whereas the CS/AO TBX2 ratio was significantly higher; at AP-induced ischaemia, CS TXB2 was significantly increased and the CS/AO TXB2 ratio was increased. A weak but significant direct correlation was found between CS/AO TXB2 ratio and coronary score. Sulphinpyrazone treatment reduced CS TXB2 levels at rest and after AP, but not the ischaemic threshold at AP.

Topics: Adult; Aged; Angina Pectoris; Blood Platelets; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Count; Sulfinpyrazone; Thromboxane A2; Thromboxane B2; Thromboxanes

1 Thromboxane B2 (TXB2) levels were measured in three sites (coronary sinus, pulmonary artery, and femoral artery) at rest and during atrial pacing in 11 patients with stable angina pectoris. 2 There was a highly significant increase in arterial TXB2 on pacing (by up to 820 pg/ml) but there was no change in the thromboxane levels at the other two sites. 3 Dazoxiben 200 mg orally abolished the increase in arterial TXB2, but had no effect on systemic, pulmonary or coronary haemodynamics, no effect on myocardial metabolism and a variable effect on atrial pacing time to angina.

Topics: Aged; Angina Pectoris; Cardiac Pacing, Artificial; Hemodynamics; Humans; Imidazoles; Male; Middle Aged; Myocardium; Oxidoreductases; Thromboxane B2; Thromboxane-A Synthase; Time Factors

1 Plasma thromboxane levels were obtained from both the coronary sinus and aorta in patients with stable angina pectoris paced to angina, and in unstable angina patients before and after dazoxiben 100 mg. 2 Although there was a wide range of values in the different groups, dazoxiben significantly reduced plasma thromboxane levels in all patients. 3 Dazoxiben had no adverse effect on coronary and systemic haemodynamics, and atrial pacing time to angina was increased from 245 +/- 41 to 308 +/- 48s (P less than 0.01).

Topics: Adult; Aged; Angina Pectoris; Coronary Circulation; Coronary Disease; Hemodynamics; Humans; Imidazoles; Middle Aged; Myocardium; Oxidoreductases; Platelet Aggregation; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

Thromboxane A2 exerts powerful effects on vascular smooth muscle tone and platelet aggregability. Previous studies have demonstrated increases in transcardiac thromboxane B2 (a stable thromboxane A2 metabolite) in patients with unstable angina and recent chest pain. To determine whether these increases in transcardiac thromboxane B2 are unique to the unstable anginal syndrome or are merely a consequence of ongoing myocardial ischemia, simultaneous ascending aortic and coronary sinus blood samples were obtained for quantitation of thromboxane B2 in 52 patients with a history of chest pain. Provocation was performed with (1) rapid cardiac pacing in 23 patients, (2) cold pressor stress in 19 patients, and (3) sustained isometric exertion in 10 patients. Of the 52 patients, only 5 had a substantial (greater than 3-fold) increase in coronary sinus thromboxane B2 in response to provocation: 1 had unstable angina and chest pain during the previous 48 hours and 4 had a myocardial infarction within the previous 6 weeks. Similarly, only 7 had a greater than 3-fold increase in the coronary sinus/aortic thromboxane B2 ratio in response to provocation: 1 had unstable angina and recent chest pain, 5 had a recent myocardial infarction, and 1 had both of these. There were no other clinical features unique to these patients. The remaining patients with similar diagnoses did not develop a marked increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio with provocation. None of the 35 patients with stable ischemic heart disease or nonischemic chest pain syndromes had a substantial increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio (p less than 0.001 for both coronary sinus thromboxane B2 and the coronary sinus/aortic thromboxane B2 ratio in comparison with the 17 patients with recent unstable angina or myocardial infarction). Thus, generous amounts of thromboxane B2 are released into the coronary circulation after provocation in some patients with unstable angina or recent myocardial infarction but not in those with stable ischemic heart disease or nonischemic chest pain syndromes.

Topics: Adult; Aged; Angina Pectoris; Aorta; Cardiac Pacing, Artificial; Cold Temperature; Coronary Disease; Coronary Vessels; Electrocardiography; Female; Humans; Isometric Contraction; Male; Middle Aged; Pain; Thromboxane B2; Thromboxanes

The effect of atrial pacing on intracoronary thromboxane production was investigated in 35 patients with stable (n = 19) or unstable (n = 16) angina. Arterial and coronary sinus thromboxane B2, the stable metabolite of thromboxane A2, myocardial lactate extraction and thermodilution coronary sinus flow were measured before, during and immediately after atrial pacing until the onset of angina. Pacing did not significantly increase coronary sinus thromboxane B2 (rest, 233 +/- 107 pg/ml; pacing, 249 +/- 154 pg/ml; postpacing, 330 +/- 309 pg/ml) (mean +/- standard deviation) despite a moderate increase in arterial thromboxane B2 (rest, 270 +/- 170 pg/ml; pacing, 387 +/- 364 pg/ml; postpacing, 446 +/- 420 pg/ml) (all changes probability [p] less than 0.05). A positive transmyocardial thromboxane B2 gradient, suggesting intracoronary thromboxane A2 production, occurred in only five patients at rest (gradient = 60 +/- 35 pg/ml). During pacing, a transmyocardial thromboxane B2 gradient was not observed despite myocardial lactate production in 18 patients. A postpacing gradient was observed in eight patients (gradient = 284 +/- 349 pg/ml). These gradients were significantly more frequent in patients who produced lactate during pacing (7 of 18) than in patients without lactate production (1 of 17) (p less than 0.05). In patients with and without a postpacing gradient, coronary vascular resistance decreased with pacing and returned to rest levels immediately after pacing, suggesting that a postpacing thromboxane gradient does not significantly alter coronary tone. These data suggest that: 1) pacing-induced angina is usually not associated with substantial intracoronary thromboxane A2 production; 2) in a minority of patients who develop intracoronary thromboxane A2 production, the amount is small and does not produce significant coronary vasoconstriction.

Topics: Angina Pectoris; Cardiac Catheterization; Cardiac Pacing, Artificial; Coronary Disease; Female; Hemodynamics; Humans; Lactates; Lactic Acid; Male; Middle Aged; Thromboxane A2; Thromboxane B2; Thromboxanes

The influence of molsidomin (4 mg i.v.) on platelet function, on the plasma concentrations of 6-oxo-PGF1 alpha, the stable metabolite of prostaglandin I2, and thromboxane B2, the stable metabolite of thromboxine A2 was determined in ten patients with coronary heart disease. Prostaglandin I2 is generated in the vessel wall and is a potent vasodilator and inhibitor of platelet aggregation, whereas thromboxane A2 is a vasoconstrictor and a proaggregatory substance. In addition, in-vitro tests were performed, too. 60 min after bolus injection a decrease of systolic and diastolic blood pressure was observed, whereas heart rate remained nearly constant. Platelet aggregation decreased significantly; the addition of PGI2 in vitro had an additive effect. The plasma concentrations of 6-oxo-PGF1 alpha increased after 60 minutes, whereas thromboxane B2 concentrations remained unchanged. In vitro, SIN1, a metabolite of molsidomin generated in the liver, led to a dose-dependent inhibition of ADP-induced platelet aggregation, whereas molsidomin was nearly inactive. Thus molsidomin shows an inhibition of platelet function besides the known antianginal properties. The vasodilatatory and platelet inhibiting effects of this compound may be due partly to a stimulation of the prostaglandin I2 synthesis in the vessel wall.

Topics: Angina Pectoris; Blood Pressure; Coronary Disease; Epoprostenol; Female; Humans; Male; Molsidomine; Muscle, Smooth, Vascular; Oxadiazoles; Platelet Aggregation; Prostaglandins F; Sydnones; Thromboxane A2; Thromboxane B2

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

Endogenous modulators of platelet aggregability and vascular tone may play a part in coronary-artery disease. We therefore measured the release of prostaglandins and thromboxane into the coronary circulation in patients with various kinds of cardiac disease. Simultaneous coronary-sinus (CS) and ascending-aortic (AO) blood samples were obtained from 60 patients for measurement of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, a prostaglandin I2 metabolite) and of thromboxane B2 (TxB2). Samples from 45 of these patients were also tested for prostaglandin E2 (PGE2) and lactate. Patients with unstable angina pectoris who reported chest pain within 24 hours of study had higher TxB2 CS/AO ratios (5.8 +/- 2.8, mean +/- S.D.) than patients whose most recent anginal pain was more than 96 hours before study (1.3 +/- 0.6; P less than 0.05), than those with nonischemic chest pain (1.2 +/- 0.4; P less than 0.05), or with valvular or congenital nonischemic heart disease (1.2 +/- 0.6; P less than 0.05). Those whose most recent anginal pain occurred 24 to 96 hours before study were distributed bimodally: the majority had low TxB2 CS/AO ratios (range, 0.5 to 2.1) like the patients in the three aforementioned groups, whereas a few had markedly elevated values (range, 10.5 to 46.6). The 6-keto-PGF1 alpha and PGE2 CS/AO ratios and myocardial lactate extraction were not significantly different among the five groups. These data suggest that local thromboxane release is associated with recent episodes of angina in patients with unstable angina pectoris, but whether this release is a cause or an effect is not yet known.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Coronary Circulation; Coronary Disease; Female; Humans; Lactates; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane B2; Thromboxanes

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

Topics: Angina Pectoris; Arachidonic Acids; Aspirin; Constriction, Pathologic; Coronary Disease; Dietary Fats; Epoprostenol; Fatty Acids, Unsaturated; Fish Oils; Humans; Platelet Aggregation; Risk; Thromboxane B2

Topics: Adult; Aged; Angina Pectoris; Blood Pressure; Brachial Artery; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Coronary Vessels; Female; Heart Rate; Humans; Lactates; Male; Middle Aged; Radioimmunoassay; Thromboxane B2; Thromboxanes; Time Factors; Vasoconstrictor Agents

Increases in endogenous free fatty acids (FFA) induced by several stimuli are associated with increases in platelet aggregates and platelet factor 4 in man. To determine if thromboxane (TxB) release is also an associated event, we measured plasma FFA and TxB2 levels before and 5 min after bolus injection of 2,500 U of heparin prior to coronary arteriography in 27 patients with angina. Significant increases in FFA occurred in all patients (p less than 0.02) and those with critical lesions (p less than 0.01), while TxB2 levels also rose (p less than 0.02, p less than 0.05, respectively). However, linear regression showed increases in FFA and TxB2 were independent. The observed TxB2 release may be due to lipolysis-induced exposure of vascular collagen or direct inhibition of platelet adenylate cyclase by heparin.

Topics: Aged; Angina Pectoris; Angiocardiography; Coronary Disease; Fatty Acids, Nonesterified; Female; Heparin; Humans; Male; Middle Aged; Prostaglandins; 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