Comparison of exercise QRS amplitude changes in patients with slow coronary flow versus significant coronary stenosis

Exercise Q, R, and S wave amplitude changes, called the QRS score, have been reported to be a marker of exercise-induced myocardial ischemia. Therefore, in this study, using the exercise QRS score, we sought to determine if slow coronary flow (SCF) phenomenon is associated with the exercise-induced myocardial ischemia. This retrospective study included 23 patients evaluated for suspected coronary artery disease and found to have SCF (group I) and 19 subjects with angiographically-defined significant coronary artery stenosis (group II). All study subjects underwent treadmill exercise testing using the modified Bruce protocol. For each subject the amplitude of the Q, R, and S waves in leads aVF and V5 was measured manually using calipers before and immediately after exercise. The QRS score was calculated by subtracting the Q, R, and S wave differences in leads aVF and V5. There was no difference between the two groups with respect to demographic properties. The peak heart rate achieved, baseline and peak systolic-diastolic blood pressure, exercise duration, and the metabolic equivalent values were similar in both groups. The maximum ST-segment depression ratio was significantly lower in patients with SCF than those of significant coronary stenosis (0.8 +/- 0.4 vs 1.3 +/- 0.5 P = 0.001, respectively). However, the exercise QRS score was found to be similar in both groups (3.3 +/- 2.3 vs 2.1 +/- 3.0 P = 0.2, respectively). The data suggest that SCF phenomenon may alone lead to myocardial ischemia even in the absence of obstructed major epicardial coronary arteries as detected by similar exercise QRS scores to those of significant coronary artery stenosis.     

Relation between electrocardiographic and scintigraphic location of myocardial ischemia during exercise in one-vessel coronary artery disease

The purpose of this study was to determine the usefulness of exercise electrocardiography in predicting the site of myocardial ischemia. Fifty-two patients were studied who had angiographically documented 1-vessel coronary artery disease (CAD) and exercise-induced reversible thallium-201 perfusion defects. The patients were divided into 2 groups: group I (28 patients) had left anterior descending CAD and group II (24 patients) had left circumflex or right CAD. There were no significant differences between the 2 groups in severity of coronary stenosis, heart rate and systolic blood pressure during exercise. The size of the perfusion defect was larger in group I than II (28 +/- 12% vs 19 +/- 10%, p less than 0.02). There was no significant difference between the 2 groups in the frequency of ST depression in the anterior, inferior or lateral electrocardiographic leads. ST depression occurred in 16 patients (57%) in group I and 11 patients (46%) in group II (difference not significant). The sensitivity of the exercise electrocardiogram was 52% using 12 leads, 50% using 3 leads (V3, V5 and aVF) and 50% using V5 alone (difference not significant). Thus, the site of ST depression during exercise is not a good predictor of the site of exercise-induced perfusion defect or anatomic site of CAD. The use of 12 leads does not improve the sensitivity of exercise electrocardiography in patients with CAD.     

Rate of left ventricular functional recovery by radionuclide angiography after exercise in coronary artery disease

To characterize determinants of the rate of recovery of left ventricular (LV) function after exercise-induced ischemia, sequential postexercise radionuclide angiography was performed prospectively in 38 consecutive patients with documented coronary artery disease (CAD). In each patient new or increased regional asynergy developed or absolute ejection fraction decreased at least 4% during exercise. Twenty patients showed immediate recovery of LV function after exercise (group 1) and 18 showed delayed recovery (group 2). Ejection fraction in the first postexercise period was significantly greater in group 1 (65 +/- 12%) than in group 2 (55 +/- 11%) (p less than 0.01). The mean number of coronary arteries with at least 70% diameter narrowing was greater in group 2 (2.7 +/- 0.5) than in group 1 (2.0 +/- 0.9) (p = 0.026); CAD score was also greater in group 2 than in group 1 (p = 0.005). The increase in LV end-diastolic volume from rest to end exercise was greater in group 2 than in group 1 (p = 0.005); neither the change in LV volume nor the change in heart rate or blood pressure after exercise separated the groups. The only independent predictor of the rate of functional recovery was the degree of exercise-induced regional myocardial asynergy (p less than 0.001). Thus, exercise radionuclide angiography in patients with CAD provides a model for evaluating postischemic myocardial function. Delayed functional recovery is associated with extensive exercise-induced regional asynergy as a result of severe CAD and is not primarily influenced by hemodynamic changes.     

Relation between heart rate and QT interval in exercise-induced myocardial ischemia

The relation between heart rate and QT interval during dynamic upright exercise on a bicycle ergometer was investigated in control subjects (n = 18) and in patients with coronary artery disease (CAD), stable angina on effort, and angiographically documented significant coronary stenoses (n = 23). Both groups had a significant negative linear relation between heart rate and QT, with a higher correlation coefficient in control subjects (r = -0.78) than in patients with CAD (r = -0.64). This response may be a result of the nonhomogeneous response to ischemia in patients with CAD, particularly with regard to the different impact of exercise-induced ischemia. When the 2 regression lines were compared, a flatter slope was found in the CAD group (p less than 0.001) as a consequence of a faster decrease in the QT-increasing rate in control subjects. It is suggested that in control subjects exercise-induced increase in adrenergic tone causes a rapid and relevant decrease in QT-interval duration. In the CAD group, exercise-induced ischemia relatively prolonged the QT interval; this may have been the result of an impairment of myocardium in response to catecholamines release during exercise or the consequence of a direct effect of exercise-induced ischemia prolonging the duration of myocardial tension.     

The prognostic value of a QRS score during exercise testing

BACKGROUND: Values of a QRS score have been positively related to the number of narrowed coronary arteries and to the extent of myocardial ischemia in radionuclide imaging techniques. HYPOTHESIS: This study was conducted to evaluate the potential prognostic information of abnormal values of this QRS score during treadmill exercise testing in patients with established coronary artery disease (CAD). METHODS: In all, 309 patients (258 men, 51 women, mean age 56.1 +/- 10.0 years) with documented CAD, underwent a treadmill exercise test and coronary arteriography at baseline. Subsequently, they were prospectively followed to a maximum of 36 months (mean follow-up 23 +/- 13 months, median 25 months). RESULTS: During the follow-up period, 20 patients (6.5%) died from acute myocardial infarction. Abnormal QRS score values were found to be significantly and independently associated with cardiac mortality (QRS < or = -4: relative risk 11.7; 95% confidence interval = 2.5-55.4; p = 0.002). CONCLUSIONS: Taking into consideration the importance of exercise testing in the management of ischemic heart disease, the use of this QRS score could be of clinical value in predicting the outcome of patients with documented CAD.     

Myocardial perfusion in silent myocardial ischemia: investigation by exercise stress myocardial tomography with thallium-201

To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (T1) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n = 36) or absence (Silent Group, n = 49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30 +/- 10% in Silent Group, 28 +/- 12% in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial T1 washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4 +/- 10% vs -16 +/- 14%, p less than 0.001). The study in patients who exhibited both silent and symptomatic ischemia showed same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia.     

Impaired left ventricular filling and regional diastolic asynchrony at rest in coronary artery disease and relation to exercise-induced myocardial ischemia

Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction. To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography. All patients had normal systolic function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response. Data obtained from 22 age-comparable normal volunteers were used for comparison. Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05). Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.     

Supine bicycle versus post-treadmill exercise echocardiography in the detection of myocardial ischemia: a randomized single-blind crossover trial.

OBJECTIVES: We sought to determine the comparative accuracy of supine bicycle exercise echocardiography (SBE) and posttreadmill exercise echocardiography (TME) in detecting myocardial ischemia in patients with known or suspected coronary artery disease (CAD). BACKGROUND: Supine bicycle echocardiography and TME have been used for evaluation of CAD. However, the comparative accuracy of these modalities in the detection of ischemia in the same patients is not known. METHODS: Seventy-four patients (age 59 +/- 9 years [mean +/- SD]) referred for evaluation of coronary disease underwent SBE (starting at 25 to 50 W with 25-W increment every 3 min) and post-TME (Bruce protocol) in a random sequence. Digitized images at baseline and maximal exercise were interpreted in a random and blinded fashion. RESULTS: Maximal heart rate was higher during TME, whereas systolic blood pressure was higher during SBE, resulting in a similar double product. At quantitative angiography (n = 67), 57 patients had coronary stenosis (>50%). During SBE, ischemia was detected in 47 patients compared with 38 patients by TME (p < 0.001). Wall motion score index at maximal exercise was higher with SBE than with TME (1.48 +/- 0.51 vs. 1.38 +/- 0.43; p < 0.001). The extent of myocardial ischemia (number of ischemic segments) was higher during SBE compared with TME (3.3 +/- 3.4 vs. 2.3 +/- 2.9 segments; p = 0.004), whereas severity of abnormal wall motion was similar. The sensitivity of SBE and TME for CAD was 82% and 75% with a specificity of 80% and 90%, respectively. Image quality was similar with both techniques. Patients and sonographers favored SBE over TME. CONCLUSIONS: During SBE and TME exercise, patients achieve a similar double product. During SBE, however, the detection of ischemia is more frequent and more extensive which, along with patient and sonographer preference, makes supine bicycle exercise a valuable stress echocardiographic modality.     

Myocardial ischemia adjacent to infarction enhances the magnitude of exercise-induced ST-segment elevation one month after myocardial infarction

The aims of this study were to compare exercise-induced ST-segment elevation with and without ischemia and to examine the relation between exercise-induced ST-segment elevation and the location of myocardial ischemia. Seventy-nine patients with first anterior myocardial infarction underwent thallium-201 exercise myocardial scintigraphy test one month after myocardial infarction. There were 37 patients showing no reversible defect (non ischemia group), 33 with reversible defect in the territory of the left descending coronary artery (homozonal ischemia group) and 9 with a reversible defect in the territory of the left circumflex or right coronary artery (remote ischemia group). There were no significant differences among the three groups with respect to infarct size, presence of dyskinesis and exercise endurance time. Patients with homozonal ischemia had the highest degree of ST-segment elevation (0.22 +/- 0.09 mV) followed by patients without ischemia (0.13 +/- 0.07 mV) and those with remote ischemia (0.09 +/- 0.08 mV, P <.01). In conclusion, Myocardial ischemia adjacent to infarction amplifies exercise-induced ST-segment elevation.     

The effect of coronary artery bypass grafting on left ventricular systolic function at rest: evidence for preoperative subclinical myocardial ischemia

Successful coronary artery bypass grafting (CABG) improves exercise-induced left ventricular (LV) dysfunction in patients with coronary artery disease (CAD), but its potential for improving resting LV function remains controversial. To assess the influence of CABG on LV function at rest, 31 CAD patients without previous myocardial infarction were studied before and 6 months after CABG by radionuclide angiography after all cardiac medicines were withdrawn. No patient had angina or ischemic electrocardiographic changes at rest. In 27 patients with patent bypass grafts, CABG significantly increased LV ejection fraction during exercise (47 +/- 11% before to 63 +/- 9% after operation, p less than 0.001), indicating reduction in exercise-induced LV ischemia. Moreover, LV ejection fraction at rest also increased (55 +/- 9 to 60 +/- 8%, p less than 0.001), with 20 of 27 patients manifesting an increase compared with preoperative values. Eleven of these 20 patients had apparently normal LV function at rest (ejection fraction and regional wall motion) before CABG. LV regional ejection fraction was computed by dividing the LV region of interest into 20 sectors. Regional analysis indicated that improved ejection fraction at rest after CABG occurred in regions developing ischemia during exercise before CABG. In 4 patients with occluded grafts, the ejection fraction at rest was unchanged by CABG globally (59 +/- 8 to 58 +/- 9%, difference not significant) and regionally. Thus, LV global and regional function at rest improved after successful CABG, even in patients with normal global LV ejection fraction and no visually detectable wall motion abnormality before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intracoronary thrombolytic therapy on exercise-induced ischemia after acute myocardial infarction

Intracoronary streptokinase (SK) therapy increases vessel patency rate after acute myocardial infarction (AMI) and thus may lead to a greater exercise-induced myocardial ischemia. This hypothesis was tested in 39 patients enrolled in an angiographically randomized trial of intracoronary SK (19 treated with SK and 20 control subjects); all patients underwent thallium-201 scintigraphy at rest before acute angiography, as well as at rest and during stress 5 to 6 weeks after AMI. The patients were classified into 2 groups based on the presence (n = 13) or absence (n = 26) of complete obstruction of the infarct-related coronary artery at the end of the acute angiography. Semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Thallium defect score at rest between admission and 5 to 6 weeks' study decreased from 10 +/- 16% units in the control group and from 23 +/- 14% units in the SK group (p = 0.01). This decrease was related to opening of the infarct-related artery (opening 23 +/- 16% vs occlusion 5 +/- 10%). The change in exercise-induced defect score was significantly (p = 0.01) larger in patients in the SK group (11 +/- 6% units) than in those in the control group (5 +/- 7% units). The perfusion defect during exercise was larger (p = 0.006) in patients with incomplete obstruction or reperfusion (10 +/- 6% units) than in patients with complete obstruction (3 +/- 7%). This difference was independent of the number of diseased coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-induced ST-segment depression: imbalance between myocardial oxygen demand and myocardial blood flow

OBJECTIVE: ST-segment depression is believed as a common electrocardiographic sign of myocardial ischemia during exercise testing. Ischemia is generally defined as oxygen deprivation due to reduced perfusion. However, the exact relationship of the ischemic definition to ST-segment depression remains unclear. This study was conducted to evaluate the correlation between myocardial oxygen demand and myocardial blood flow (MBF) when ischemic (horizontal or downsloping) ST-segment depression of > or = 0.1 mV 80 ms after the J point developed during low-level exercise. METHODS AND RESULTS: Seventy-two patients with angiographically proven coronary artery disease (CAD) and 9 healthy volunteers underwent exercise positron emission tomography (PET). Myocardial oxygen demand was defined as a rate-pressure product (RPP, heart rate x systolic blood pressure) during exercise and MBF was quantified by nitrogen-13 ammonia perfusion PET. The myocardial demand-supply balance (MDSB) index was calculated from the MBF ratio (values during exercise/values at rest) against the RPP ratio (values during exercise/values at rest). The MDSB index was significantly lower in patients with ischemic ST-segment depression than in patients with non-ischemic ST depression and healthy volunteers (0.82 +/- 0.16 vs. 1.02 +/- 0.17, p < 0.0001 and vs. 0.99 +/- 0.14, p = 0.0109). Further, the presence of inadequate increase in MBF of < or = 10% (2 SD below the mean % value of healthy volunteers) during exercise in regional myocardium perfused by stenotic CAD significantly correlated with exercise-induced ischemic ST-segment depression (p = 0.0105). CONCLUSIONS: Our study could demonstrate that exercise-induced ischemic ST-segment depression is associated with myocardial ischemia due to exercise-induced imbalance between myocardial oxygen demand and global and regional MBF supply in patients with proven CAD.     

New coronary artery disease index based on exercise-induced QRS changes

Exercise-induced changes in Q, R, and S wave amplitudes have been reported to detect coronary artery disease but with low specificity, low sensitivity, or both; it was hypothesized that their incorporation into a composite index (Athens QRS score) might improve specificity and sensitivity. For this purpose 246 patients were analyzed retrospectively and 160 prospectively. All patients underwent maximal exercise testing with a standard Bruce protocol and coronary arteriography as part of the diagnostic evaluation for possible or definite coronary artery disease. The Athens QRS score was decreased as the number of obstructed coronary arteries increased (normal coronary arteries = 7.85 +/- 5.23 mm, one-vessel disease = 5.2 +/- 5.3 mm, two-vessel disease = -0.85 +/- 5.4 mm, three-vessel disease = -3.5 +/- 5.8 mm; p less than 0.0001); the score was unrelated to exercise-induced ST segment depression, and negative (less than 0) scores were always associated with coronary artery disease. An Athens QRS score of 5 mm predicted coronary artery disease with sensitivity ranging from 75% to 86% and a specificity ranging from 73% to 79%, values higher than those of the Q wave (75% and 50%, respectively), R wave (65% and 55%), and S wave (70% and 10%) and of the ST segment depression (62% and 70%). It is concluded that exercise-induced changes in the QRS complex provide a useful index not only for the diagnosis but also for the assessment of severity of coronary artery disease.     

Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study

Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference).(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of QT dispersion in the interpretation of treadmill exercise electrocardiograms of patients without exercise-induced chest pain or ST-segment depression

It has recently been reported that increased QT dispersion seen on standard 12-lead electrocardiograms (ECGs) reflects transient myocardial ischemia. The present study investigates whether increased QT dispersion induced by exercise is a useful indicator for detecting significant coronary stenosis in patients who do not have chest pain or significant ST-segment depression in response to exercise. We studied 135 consecutive patients (mean age +/- SD, 55 +/- 9 years; 97 men and 38 women) who complained of anginal chest pain and who did not have exercise-induced chest pain or significant ST-segment depression during treadmill exercise electrocardiography. Coronary angiography was performed in all of patients. Of the 135 patients, 97 had no significant coronary stenosis, 25 had 1-vessel coronary artery disease (CAD), and 13 had multivessel CAD. QT dispersion immediately after exercise was significantly greater in the group with significant coronary stenosis than without significant coronary stenosis (62 +/- 13 vs 40 +/- 14 ms, p <0.0001). When QT dispersion >/=60 ms immediately after exercise was considered a positive result, this indicator had a sensitivity of 74%, a specificity of 85%, and an accuracy of 81% for the diagnosis of significant coronary stenosis. In conclusion, we have shown that QT dispersion immediately after exercise is useful for detecting significant CAD in patients who do not have exercise-induced chest pain or significant ST-segment depression.     

Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.     

Effects of infusion of L-arginine on exercise-induced myocardial ischemic ST-segment changes and capacity to exercise of patients with stable angina pectoris.

BACKGROUND: Results of recent studies show that intracoronary administration of L-arginine, the precursor of nitric oxide, restores endothelial function in subjects with coronary risk factors and minimal coronary artery lesions. However, few investigators have examined the clinical feasibility of using L-arginine for treatment of myocardial ischemia due to coronary artery disease. OBJECTIVE: To examine the effect of supplementary L-arginine on exercise-induced myocardial ischemia and capacity to exercise of patients with stable effort angina pectoris. METHODS: Twelve patients confirmed to have a single epicardial coronary artery stenosis underwent two treadmill exercise tests after infusion of 10% L-arginine solution or placebo (5% dextrose) according to a randomized single-blind crossover design on two days separated by an interval of less than 1 week. Respiratory gas exchange kinetics were measured and myocardial ischemia was estimated by electrocardiography before and during exercise. RESULTS: Infusion of L-arginine did not alter exercise-induced changes in heart rate and blood pressure, and objective parameters of capacity to exercise. Exercise-induced maximum ST-segment depression (by 2.1 +/- 0.9 mm; with L-arginine; by 1.9 +/- 0.9 mm with placebo, NS) and onset of 1 mm ST-segment depression after exercise (after 261 +/- 131 s with L-arginine; after 247 +/- 136 s with placebo, NS) also remained unchanged. However, ST-segment depression was restored to baseline after exercise significantly more quickly after infusion of L-arginine than it did with placebo (after 331 +/- 167 s with L-arginine; after 400 +/- 165 s with placebo: P < 0.01). CONCLUSION: Intravenous administration of L-arginine did not alter capacity to exercise or the threshold for exercise-induced myocardial ischemia. However, it did reduce the time taken for recovery after ST-segment depression, suggesting that an earlier resolution of exercise-induced myocardial ischemia occurred.     

Comparison of platelet function during exercise in normal subjects and coronary artery disease patients: Potential role of platelet activation in myocardial ischemia

Platelet function parameters as influenced by exercise stress were evaluated in 22 patients with coronary artery disease (CAD) and in 13 normal subjects. Upon exercise stress, 14 CAD patients exhibited positive tests and eight exhibited negative tests. Platelet counts during exercise increased similarly in normal and CAD patients. Platelet aggregation response to ADP was unaffected by exercise both in normal and CAD patients. Platelets from 7 of the 14 CAD patients with positive stress tests had increased sensitivity to endoperoxide analog (U-46619) defined as less than 200 ng/ml U-46619 required for 50% platelet aggregation. Resting plasma beta-thromboglobulin (B-TG) levels, an index of in vivo platelet activation, were significantly higher in CAD patients compared to normal subjects (74 +/- 7 and 41 +/- 5 ng/ml, respectively; p less than 0.02). During exercise plasma B-TG levels increased in normal subjects to 60 +/- 5 ng/ml. In contrast, B-TG levels increased to 102 +/- 14 ng/ml in CAD patients (p less than 0.01 compared to normal subjects). These increases were transient and B-TG declined to preexercise values soon after exercise. Eleven of the 12 CAD patients with positive exercise stress tests had increases in plasma B-TG levels, whereas only three of the eight CAD patients with negative stress tests had any increase. These observations of increased platelet activation in certain CAD patients during exercise may be related to exercise-induced myocardial ischemia.     

Alterations in myocardial metabolism and function at rest in stable angina pectoris: relations with the amount of exercise-induced thallium-201 perfusion defect

The relation between the amount of exercise-induced ischemia and alterations in left ventricular (LV) function and metabolism at rest was studied in 18 coronary patients with stable angina pectoris. An ischemic defect area score was computed from quantitative exercise thallium-201 (Tl-201) scintigraphy; this estimation of the amount of ischemic myocardium was used to classify the patients in group I (n = 8; score less than 15%, mean 6.7 +/- 2.5%) and II (n = 10; score greater than 15%; mean 27.2 +/- 8.9%). Hemodynamics and metabolism were studied in basal state. No patient had anginal pain during the study, and the extent of angiographic coronary artery disease (CAD) was comparable in the two groups. Heart rate, aortic pressure, coronary blood flow, and myocardial oxygen uptake were also similar in both groups. However, ejection fraction was reduced in group II (51 +/- 13 vs 63 +/- 5%; p less than 0.01) and LV relaxation was impaired as shown by the increase in time-constant of isovolumic pressure fall (55 +/- 16 vs 44 +/- 6 ms in group I; p less than 0.05); the LV end-diastolic pressure was also increased in group II (19 +/- 8 vs 10 +/- 4 mmHg in group l; p less than 0.05). Furthermore, in group II, myocardial lactate uptake was reduced (4 +/- 19 vs 30 +/- 29 mumole/min in group I; p less than 0.01) and the productions of alanine and glutamine were augmented (-7.5 +/- 4.4 vs -4.6 +/- 1.6 mumole/min in group I; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)