thromboxane-b2 and Angina--Unstable

Evidence suggests that unstable angina, non-Q-wave myocardial infarction and Q-wave myocardial infarcts represent a continuum, such that transient reduction in coronary blood flow associated with platelet aggregation and dynamic vasoconstriction at sites of coronary artery stenosis and endothelial injury lead to abrupt development of unstable angina. Factors potentially responsible for the conversion from chronic to acute coronary artery disease include endothelial injury at sites of stenosis. The endothelial injury may be the result of plaque fissuring or ulceration, hemodynamic factors (including systemic arterial hypertension or flow shear stress), infection, smoking, coronary arteriography or balloon angioplasty. Clinical and experimental animal studies suggest that interference with thromboxane and serotonin contributions to platelet aggregation and dynamic coronary artery constriction may prevent chronic coronary artery disease syndromes from converting to acute disease. To protect against this process may require both thromboxane and serotonin receptor antagonists or a combination of thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist. Further studies are needed to test this hypothesis.

Topics: Angina, Unstable; Animals; Coronary Disease; Dogs; Myocardial Infarction; Receptors, Prostaglandin; Receptors, Serotonin; Receptors, Thromboxane; Serotonin; Thromboxane A2; Thromboxane B2

To observe the effectiveness of Modified Nuan Gan Jian Jiao Nang (MNGJ [symbol: see text] Modified Liver-Warming Capsule) in treating unstable angina pectoris.. Sixty-six eligible cases were assigned randomly into a treatment group and a control group and treated for 3 weeks.. MNGJ produced an effect in reducing episodes, improving the abnormal findings in electro-cardiogram (ECG) (P<0.05) significantly, and decreasing myocardial oxygen consumption (P<0.05). In addition, it could decrease the plasma TXB2 level and increase 6-keto-prostaglandin F1alpha (6-Keto-PGF1alpha) level (P<0.01).. MNGJ was quite effective in treating unstable angina pectoris, suggesting that the treatment of the disease could start from the liver.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Angina, Unstable; Diagnosis, Differential; Drugs, Chinese Herbal; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Phytotherapy; Thromboxane B2

The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C4 and thromboxane (TX) A2 biosynthesis in unstable angina.. Urinary LTE4 and 11-dehydro-TXB2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions. LTE4 excretion showed a time-dependent decrease in the 6-MP group but did not decrease during placebo. Furthermore, during myocardial ischemia, LTE4 was significantly higher before 6-MP infusion than during steroid therapy. In contrast, 11-dehydro-TXB2 did not differ significantly during 6-MP versus placebo. Myocardial ischemia elicited by stress test in the stable angina patients was not accompanied by any change in LTE4 and 11-dehydro-TXB2, thus ruling out a role of ischemia per se in the induction of increased eicosanoid production.. Increased production of vasoactive LT and TX may occur in unstable angina despite conventional antithrombotic and antianginal treatment. Glucocorticoids can suppress LTC4 biosynthesis in the short term and may provide an interesting tool to explore the pathophysiological significance of inflammatory cell activation in this setting.

Topics: Adult; Angina, Unstable; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Double-Blind Method; Eicosanoids; Female; Glucocorticoids; Humans; Leukotriene E4; Male; Methylprednisolone; Middle Aged; Myocardial Ischemia; Thromboxane B2

We have previously reported aspirin failure in suppressing enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation during the acute phase of unstable angina. The recent discovery of a second prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or mitogenic stimuli, prompted us to reexamine TXA2 biosynthesis in unstable angina as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2 despite a comparable impact on platelet PGHS-1.. We randomized 20 patients (15 men and 5 women aged 59+/-10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB2 was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA2 biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value; n=99) in the indobufen group (P<.001). There were 16 samples (21%) with 11-dehydro-TXB2 excretion >200 pg/mg creatinine among patients treated with aspirin versus 6 such samples (6%) among those treated with indobufen (P<.001). In vitro and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations. In contrast, aspirin could only inhibit monocyte PGHS-2 transiently at very high concentrations.. We conclude that in unstable angina, episodes of aspirin-insensitive TXA2 biosynthesis may reflect extraplatelet sources, possibly expressing the inducible PGHS in response to a local inflammatory milieu, and a selective PGHS-2 inhibitor would be an ideal tool to test the clinical relevance of this novel pathway of arachidonic acid metabolism in this setting.

Topics: Aged; Angina, Unstable; Aspirin; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Humans; Isoenzymes; Isoindoles; Male; Membrane Proteins; Middle Aged; Phenylbutyrates; Prostaglandin-Endoperoxide Synthases; Reference Values; Thromboxane A2; Thromboxane B2

To explore the effect of Buyang Huanwu Decoction (BYHWD) on the platelet function and fibrinolytic activity of unstable angina pectoris patients.. Using randomized single blind method divided 60 unstable angina pectoris patients into conventional treatment (control) group and conventional plus BYHWD (TCM) group.. BYHWD could lower the levels of platelet aggregation, thromboxane B2 and the inhibitor of fibrinolysinogen activator (P < 0.05), but the activity of histo-type of fibrinolysinogen activator was enhanced.. BYHWD was effective in treating unstable angina pectoris.

Topics: Adult; Aged; Angina, Unstable; Antifibrinolytic Agents; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Plasminogen Inactivators; Platelet Aggregation; Platelet Aggregation Inhibitors; Single-Blind Method; Thromboxane B2; Tissue Plasminogen Activator

Patients with unstable angina pectoris have increased thrombocyte aggregation and disturbances in serum prostaglandin balance. As a pilot project, we conducted a single-blind investigation of 24 patients with unstable angina pectoris treated with dilthiazem (n = 12, 240-360 mg) or verapamil (n = 12, 240-360 mg) for ten days. At the commencement of the investigation, both patient groups had hyperaggregating thrombocytes and increased serum-thromboxan-B2 (TXB2) as compared to healthy individuals (p < 0.01). In the patient group treated with dilthiazem, the aggregation threshold rose (p < 0.01), and the serum TXB2 values fell to approximately normal (p < 0.05). In the patient group treated with verapamil, no significant changes were observed in the measurements registered. The difference between the two groups remained significant during the entire therapeutic period (p < 0.01). Thus, dilthiazem appears to counteract thrombocyte aggregation in patients with unstable angina pectoris.

Topics: Angina, Unstable; Diltiazem; Drug Evaluation; Female; Humans; Male; Middle Aged; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Thromboxane B2; Verapamil

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

Topics: Angina, Unstable; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Thromboxane B2; Thromboxanes

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

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 evaluate the effects of aspirin on thrombin generation in patients with unstable angina, plasma levels of thrombin-antithrombin III complex (TAT) as a new marker of thrombin generation and of 11-dehydro-thromboxane B2 (11-dehydro-TXB2) as an indicator of platelet activation were measured in 18 patients with unstable angina, including 8 patients with prolonged rest angina (> 15 minutes). Aspirin DL-lysine (900 mg) was administered intravenously to 9 of the 18 patients (aspirin group); the other 9 were not given aspirin during the first 24 hours of hospitalization (non-aspirin group). Clinical characteristics, angiographic features and medications other than aspirin were similar between the 2 groups. Levels of plasma TAT and 11-dehydro-TXB2 were significantly higher (p < 0.05) in patients with prolonged rest angina than in those without the condition (n = 10). In 5 patients with prolonged rest angina who received aspirin, plasma TAT levels (ng/ml) were significantly decreased (4.52 +/- 1.18 at baseline, 2.50 +/- 0.65 at 1 hour and 2.16 +/- 0.42 at 24 hours after aspirin administration, p < 0.01) with a significant decrease in plasma 11-dehydro-TXB2 levels. However, the reduction in TAT after aspirin administration was slight in patients without prolonged rest angina (n = 4). In contrast, levels of plasma TAT and 11-dehydro-TXB2 in the non-aspirin group remained unchanged during the study period. These results suggest that aspirin rapidly reduces thrombin generation through inhibition of platelet activity in patients with unstable angina with prolonged rest angina.

Topics: Aged; Aged, 80 and over; Angina, Unstable; Antithrombin III; Aspirin; Blood Coagulation; Female; Humans; Lysine; Male; Middle Aged; Peptide Hydrolases; Platelet Aggregation Inhibitors; Thrombin; Thromboxane B2

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

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

Topics: Adult; Aged; Angina, Unstable; Circadian Rhythm; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Thromboxane B2

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

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

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

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

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

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

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

Topics: Adult; Angina, Unstable; Anticoagulants; Coronary Disease; Coronary Vessels; Electrocardiography; Female; Humans; Male; Methacrylates; Middle Aged; Myocardial Infarction; Perfusion; Stroke Volume; Thiophenes; Thromboxane A2; Thromboxane B2; Ticlopidine; Tomography, Emission-Computed; Urokinase-Type Plasminogen Activator

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