Inhibition of platelet aggregation by prostacyclin is attenuated after exercise in patients with angina pectoris.

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.     

Effects of the platelet inhibitor ticlopidine on exercise tolerance in stable angina pectoris

Coronary blood flow might be reduced by platelet aggregatesor by vasospasm induced by platelet-produced thromboxane A2.Therefore the effects of the platelet inhibitor ticlopidine(500 mg daily) on platelet function and on exercise tolerancewere investigated in a double-blind placebo-controlled studyin 38 middle-aged men with stable incapacitating angina pectoris.Before and after 4 and 8 weeks of treatment, exercise testswere performed in warm and cold environments. The in vitro plateletreactivity to ADP was determined at rest and the plasma levelsof beta-thromboglobulin (BTG) and platelet factor 4 (PF4) weremeasured before and immediately after exercise. There were nosigns of increased platelet activity at rest or after exerciseas judged by the levels of BTG and PF4. Despite a potent inhibitionof platelet reactivity to ADP in vitro during ticlopidine treatment,the exercise tolerance was reduced in exercise tests in bothwarm and cold environments and in daily life. Therefore plateletactivity does not seem to play any significant role in exercisetolerance in the stable phase of angina pectoris.     

Acute vigorous exercise primes enhanced NO release in human platelets

Activation of platelets by acute vigorous exercise has been demonstrated by various parameters, including an increase in agonist-induced platelet [Ca2+]i levels. However, direct evidence is lacking regarding how acute exercise affects platelet-derived NO. Twenty-three healthy male non-smokers (21-59 years) underwent a symptom-limited treadmill exercise test. Washed platelets were prepared from blood samples obtained before and immediately after exercise. All subjects completed at least Bruce stage 2 and were each negative for ischemia. With a low dose (2 microg/ml) of collagen, NO release from washed platelets, detected by the NO-selective microelectrode, was significantly increased after exercise (pmols/10(8) platelets, before: 0.64+/-0.11, after: 1.03+/-0.18; P<0.005) without changes in aggregation ability. This enhanced NO release was accompanied by increased platelet [Ca2+]i levels (before: 232+/-25, after: 296+/-37; P<0.01). With a high dose (5 or 10 microg/ml) of collagen, NO release and aggregation were both modestly, but significantly, enhanced after exercise. The exercise-induced enhancement of platelet NO release in response to collagen was also suggested by increase in platelet cyclic guanosine monophosphate accumulation and augmenting effect of N(G)-monomethyl-L-arginine on platelet aggregation. In summary, acute strenuous exercise primes enhanced NO release and may play a protective role against exercise-induced activation of platelets in normal subjects.     

Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris

This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the A.M. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p < or = 0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p < 0.05) compared with either COER-24 or amlodipine plus atenolol. COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris. COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 A.M. to 12 noon.     

Event-free survival in patients after an acute coronary event with exercise-induced normalization of the T-wave

BACKGROUND: Risk stratification of patients with unstable angina or non-Q-wave myocardial infarction (MI) is an unresolved clinical problem. The prognostic value of T-wave normalization (TWN) during exercise has not been studied in this group of patients. HYPOTHESIS: Event-free survival in clinically stable patients after an acute coronary event without ST-segment elevation can be predicted by the presence of exercise-induced TWN. METHODS: Sixty-five patients (43 men and 22 women, mean age 62+/-10 years) entered the study. The diagnosis of unstable angina and non-Q-wave MI was made in 40 and 25 patients, respectively. A treadmill exercise test was performed in all patients after clinical stabilization. The patients were divided into three groups: those with negative baseline T waves and exercise-induced TWN (Group 1); those with negative baseline T waves, but without TWN (Group 2); and those with positive baseline T waves (Group 3). The patients were followed up for 6 months. RESULTS: During follow-up, serious cardiovascular complications occurred in 15 (23%) patients. These included exacerbation of ischemic heart disease (14 patients) and acute MI (1 patient). Event-free survival was greater in patients in Group 1 (95%) than in those in Group 2 (68%, p < 0.034) or Group 3 (71%, NS). Among all patients studied, exercise-induced TWN was predictive of event-free survival with a sensitivity of 38% and a specificity of 93%. CONCLUSIONS: In clinically stable patients after an acute coronary event without ST-segment elevation, exercise-induced TWN is a specific but n ot sensitive predictor of event-free survival after 6 months.     

Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study.

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.     

Amlodipine in patients with stable angina pectoris treated with nitrates and beta-blockers. The influence on exercise tolerance, systolic and diastolic functions of the left ventricle.

The effects of 5 and 10 mg of amlodipine and of placebo were compared in 21 patients with stable angina pectoris and multivessel coronary artery disease. The blind comparison was performed by means of bicycle ergometry and stress echocardiography using esophageal stimulation of the left heart atrium. All patients subsequently received placebo, amlodipine 5 mg and 10 mg for 2 weeks. In bicycle ergometry both doses of amlodipine in comparison with placebo significantly lowered the ST segment depression in lead V5 and prolonged the time to onset of angina. The exercise duration was significantly prolonged only after 10 mg of amlodipine. In stress echocardiography 10 mg of amlodipine significantly improved ejection fraction and reduced wall motion score during stimulation and increased peak velocity of relaxation of left ventricular posterior wall at rest and immediately after stimulation. In the patients with left ventricular end-diastolic pressure < or = 20 mmHg, amlodipine reduced the ratio of peak transmitral flow velocity in atrial contraction to that in early diastole (A/E) at rest and shortened deceleration time at rest and immediately after stimulation. Amlodipine in patients with stable angina pectoris significantly improved the exercise tolerance and the function of the left ventricle in a dose-dependent way. Amlodipine was well tolerated.     

Usefulness of QT dispersion immediately after exercise as an indicator of coronary stenosis independent of gender or exercise-induced ST-segment depression

Several recent studies suggest that QT dispersion on a standard 12-lead electrocardiogram is a clinically useful indicator of significant coronary stenosis. In this study, we compared the diagnostic accuracy of QT dispersion immediately after exercise as an indicator of coronary stenosis in men and women, and in the presence or absence of exercise-induced significant ST-segment depression. The subjects were 273 consecutive patients (mean age 56 ± 9 years; 190 men and 83 women) without a history of myocardial infarction who underwent treadmill exercise electrocardiography and coronary angiography for evaluation of angina. Of these, 146 patients had no significant coronary stenosis, 61 had single-vessel disease, 56 had multivessel disease, and 10 had left main coronary artery disease. QT dispersion immediately after exercise was significantly greater in patients with significant coronary stenosis than in those without (64 ± 14 vs 39 ± 14 ms, p <0.01). QT dispersion immediately after exercise was significantly more sensitive in men (sensitivity 75%; specificity 85%) and significantly more specific in women (sensitivity 77%, specificity 88%) than exercise-induced significant ST-segment depression (men: sensitivity 62%, specificity 74%; women: sensitivity 81%, specificity 68%) as an indicator of significant coronary stenosis. The addition of factors such as gender and the presence or absence of exercise-induced significant ST-segment depression did not significantly alter the sensitivity and specificity of QT dispersion immediately after exercise for detecting significant coronary stenosis (patients with significant ST-segment depression: sensitivity 77%, specificity 88%; patients without significant ST-segment depression: sensitivity 72%, specificity 86%). In conclusion, QT dispersion immediately after exercise is a clinically useful indicator of significant coronary stenosis independent of gender or the presence or absence of exercise-induced significant ST-segment depression.     

Comparison of slow-release pindolol, standard pindolol, and propranolol in angina pectoris

Twenty-two patients with chronic, stable, exercise-induced angina pectoris were assessed during periods of therapy with propranolol, standard-formulation pindolol, and a slow-release preparation of pindolol. Patients maintained diaries of the frequency of angina pectoris and nitroglycerin consumption and underwent treadmill exercise testing at 2 weekly intervals. No significant differences were observed in nitroglycerin consumption or anginal frequency during these 3 treatment programs. Resting heart rates were higher with pindolol than with propranolol, but no differences were noted between periods on standard and slow-release pindolol. Systolic and diastolic blood pressures were similar during therapy with these 3 treatment programs. Treadmill walking time to the development of moderate angina and systolic and diastolic blood pressure was similar during treatment with propranolol, standard-formulation pindolol, and slow-release pindolol. Exercise heart rates were slightly higher during therapy with slow-release pindolol than during standard-formulation pindolol. It is concluded that propranolol, pindolol, and slow-release pindolol are equally effective in the management of patients with chronic, stable, exercise-induced angina.     

Myocardial infarct of effort with normal coronaries. Study of in vivo platelet activation

Platelet activation may play a part in causing myocardium infarction with angiographically normal coronary arteries. We investigated this possibility by performing ergometric stress testing in a series of 9 patients (Group A) who had suffered myocardial infarction after a violent effort with angiographically documented coronary insufficiency responsible for a stable effort angina (Group B) and 11 healthy subjects (Group C). Blood samples were taken separately before exercise, at the peak of exercise, and during the recovery period. Platelet morphology, a sensitive indication of the degree of platelet activation, was studied by phase contrast microscopy after immediate fixation of the blood. The percentage of non-discoidal platelets presenting with one or several spicules was measured. At the same time, the plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured. At rest, there was no difference in platelet morphology or specific platelet proteins between the 3 groups. At the peak effort, there was a significant increase of the number of morphologically modified platelets in Groups A and B but not in healthy subjects. This platelet activation could not be linked to the presence of myocardial ischaemia because it was found both in patients with a negative maximal exercise stress test (Group A). Finally, no increase of the plasma concentrations of the platelet protein was observed in any of the groups.     

Amlodipin versus Nifedipin retard Eine randomisierte Doppelblindstudie zum Vergleich der Langzeitwirksamkeit und Verträglichkeit von Amlodipin und Nifedipin retard in der Monotherapie der chronisch stabilen Angina pectoris

PATIENTS AND METHOD: This double-blind study compared the efficacy and safety of once daily amlodipine (5-10 mg/day) vs twice daily nifedipine (40-80 mg/day) in 244 patients with chronic stable angina pectoris. Efficacy was assessed after 4 and 24 weeks by bicycle exercise test. RESULTS: No statistically significant differences were found between the two treatment groups at the end of treatment with regard to the ergometry parameters determined (maximum ST segment deviation, maximum workload in watts, maximum exercise duration and time to 0.1 mV ST segment depression). Furthermore, the two treatment groups were comparable with regard to the effected reduction in anginal attacks and short acting nitrate consumption. The incidence of adverse events was lower in the amlodipine relative to the nifedipine group (11.5% vs 19.1%). CONCLUSION: The results of this study show that once daily amlodipine offers comparable antianginal and antiischemic efficacy as twice daily sustained release nifedipine in the monotreatment of chronic stable angina pectoris. Given the lower incidence of adverse events with amlodipine and its convenient once daily dosing regimen, however, amlodipine may help to enhance patient compliance.     

Exercise induces in vivo platelet activation in patients with coronary artery disease and in healthy individuals

Recently, conflicting results have been published about a possible relationship between platelet activity and exercise-induced myocardial ischemia. The present study was performed to investigate platelet behavior during a graded symptom-limited bicycle ergometer test both in relation to the intensity of exercise and to exercise-induced myocardial ischemia. Plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were measured by radioimmunoassays in 53 patients who had had acute myocardial infarction 10 weeks before the study and, for comparison, in 9 healthy individuals. In the whole group of the 53 patients there was no significant alteration in platelet-specific proteins during exercise, whereas physical activity induced a 2- to 3-fold increase in beta-TG and PF4 levels in the controls. However, on differentiation of the patients as to their individual exercise performance, significant exercise-associated platelet activation was demonstrable in those who reached more than 75% of their calculated maximal working capacity, whereas no correlation was found between platelet activity and exercise-induced myocardial ischemia. Thus, the results from this study indicate that in vivo platelet activation is a physiological phenomenon which occurs when a certain degree of physical intensity is exceeded, independent of the precipitation of myocardial ischemia.     

Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.     

Does exercise-induced myocardial ischaemia cause enhanced platelet activation and fibrin formation in patients with stable angina and severe coronary artery disease?

In this study, betathromboglobulin (BTG) and fibrinopeptideA (FPA) in peripheral venous blood were measured in 20 patientswith stable angina pectoris before and immediately after exercise-inducedmyocardial ischaemia; in 5 of the 20 patients stable anginawas associated with typical peripheral artery disease. A totalof 10 patients with angiographically documented peripheral arterydisease without angina and 10 normal volunteers were taken ascontrol groups. BTG and FPA in the 15 patients with stable anginabefore exercise were 41±14 ng ml^-1 and 2.3±09ng ml^-1 and were not statistically different from the valuesin normal controls; after exercise-induced myocardial ischaemiano significant increase occurred in these patients. Conversely,in the 5 patients with stable angina associated with peripheralartery disease BTG and FPA before exercise were 6l±10ng ml^-1 and 3.5±0.8 ng ml^-1 and increased to 114±14ng ml^-1 (P<0.001) and 4.l±0.5 ng ml^-1 (P<0.01):These results were similar to those found in the 10 patientswith isolated peripheral artery disease.We conclude that BTGand FPA in peripheral venous blood in patients with stable anginaare not elevated either at rest or after exercise-induced myocardialischaemia. Elevated values of BTG and FPA in patients with stableangina may reflect a major interaction between blood and atheroscleroticvessel wall, suggesting the presence of associated atheroscleroticlesions in peripheral artery disease.     

Monotherapy with amlodipine or atenolol versus their combination in stable angina pectoris

BACKGROUND: The basic cause of angina pectoris is imbalance between the metabolic needs of the myocardium and the capacity of the coronary circulation to deliver sufficient oxygenated blood to satisfy these needs. HYPOTHESIS: The study was undertaken to evaluate whether the effect of combined amlodipine and atenolol therapy on patients with stable angina pectoris and with ST-depression during exercise testing and 48-h ambulatory electrocardiographic monitoring is superior to that of either agent given alone. METHODS: Patients with stable angina pectoris and ST depression during exercise and ambulatory monitoring were randomized to receive amlodipine (n = 116) or atenolol (n = 116), or both (n = 119). All patients were also treated with short- and long-acting nitrates. The design was a double-blind, randomized, triple-arm parallel group study with 10 weeks of administration of the test medication. RESULTS: In terms of time to onset of ST depression > 1 mm, time to onset of angina, total exercise time, maximum achieved workload, and peak intensity of angina, amlodipine and atenolol alone were as effective as their combination. During ambulatory monitoring, atenolol was more effective than amlodipine regarding total time and number of ST-depression episodes, and as effective as the combined drugs. CONCLUSION: For individual patients with stable angina pectoris, combination of a beta blocker with a calcium antagonist is not necessarily more effective than either drug given alone.     

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.     

Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction,but its reduction is not related to ischemia

Objectives. This study sought to assess neutrophil activation in acute coronary syndromes and its relation to ischemic episodes.Background. Neutrophil activation has been reported in unstable angina and acute myocardial infarction; however, it is not clear whether it is related exclusively to ischemia-reperfusion injury.Methods. We measured the index of intracellular myeloperoxidase in 1) patients with unstable angina, myocardial infarction, variant angina and chronic stable angina and in normal subjects (protocol A); and 2) in patients with unstable angina and acute myocardial infarction during the first 4 days of the hospital period (protocol B). To assess whether neutrophil activation was triggered by ischemia, the myeloperoxidase intracellular index was analyzed before and after spontaneous ischemic episodes and before and after ischemia induced by an exercise stress test in 10 patients with chronic stable angina. In 11 patients with unstable angina, we also compared values of the myeloperoxidase intracellular index at entry with those after waning of symptoms.Results. In protocol A, the myeloperoxidase intracellular index was significantly reduced in patients with unstable angina and acute myocardial infarction compared with patients with stable and variant angina and normal subjects (p < 0.01). In protocol B, the myeloperoxidase intracellular index did not change over time in patients with unstable angina and myocardial infarction. However, in 11 patients with waning symptoms, the myeloperoxidase intracellular index was significantly higher after symptoms had waned (p < 0.05). In patients with unstable angina, 23 ischemic episodes were studied; no changes in the myeloperoxidase intracellular index were observed. In 10 patients with chronic stable angina and positive exercise stress test results, no significant differences in the myeloperoxidase intracellular index were observed after stress-induced ischemia.Conclusions. Our study confirms that neutrophils are activated in acute coronary syndromes but suggests that their activation may not be only secondary to ischemia-reperfusion injury.     

Exercise-induced myocardial ischemia in patients with coronary artery disease: lack of evidence for platelet activation or fibrin formation in peripheral venous blood

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.     

Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.     

Assessment of biochemical aspirin resistance at rest and immediately after exercise testing.

Some aspirin-treated patients experience thromboembolic events, a phenomenon termed 'aspirin resistance', which may be clinical or biochemical by definition. Physical exercise is known to enhance platelet secretion and aggregability. To evaluate the presence of biochemical aspirin resistance at rest and immediately after exercise in individuals with stable coronary artery disease or coronary artery disease risk factors. We prospectively enrolled 101 patients who had received 100 or 300 mg/day enteric-coated aspirin for at least 7 days. Biochemical aspirin resistance (defined as normal collagen-epinephrine closure time < 165 s) was studied using the standardized platelet function analyzer. Of the 101 patients, 63 were aspirin sensitive both at rest and immediately after exercise, 18 exhibited biochemical aspirin resistance both at rest and after exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin resistance immediately after exercise. The results of exercise testing were similar in all three groups (each P > 0.05). Our results indicate that in almost 20% of the patients, aspirin did not seem to protect against exercise-induced platelet activation, despite the presence of aspirin sensitivity at rest. We did not, however, determine the extent to which the biochemical aspirin resistance noted in our study applied to clinical events.