Comparison of the ramp versus standard exercise protocols

To compare the hemodynamic and gas exchange responses of ramp treadmill and cycle ergometer tests with standard exercise protocols used clinically, 10 patients with chronic heart failure, 10 with coronary artery disease who were asymptomatic during exercise, 11 with coronary artery disease who were limited by angina during exercise and 10 age-matched normal subjects performed maximal exercise using six different exercise protocols. Gas exchange data were collected continuously during each of the following protocols, performed on separate days in randomized order: Bruce, Balke and an individualized ramp treadmill; 25 W/stage, 50 W/stage and an individualized ramp cycle ergometer test. Maximal oxygen uptake was 16% greater on the treadmill protocols combined (21.4 +/- 8 ml/kg per min) versus the cycle ergometer protocols combined (18.1 +/- 7 ml/kg per min) (p less than 0.01), although no differences were observed in maximal heart rate (131 +/- 24 versus 126 +/- 24 beats/min for the treadmill and cycle ergometer protocols, respectively). No major differences were observed in maximal heart rate or maximal oxygen uptake among the various treadmill protocols or among the various cycle ergometer protocols. The ratio of oxygen uptake to work rate, expressed as a slope, was highest for the ramp tests (slope +/- SEE ml/kg per min = 0.80 +/- 2.5 and 0.78 +/- 1.7 for ramp treadmill and ramp cycle ergometer, respectively). The slopes were poorest for the tests with the largest increments in work (0.62 +/- 4.0 and 0.59 +/- 2.8 for the Bruce treadmill and 50 W/stage cycle ergometer, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nitroglycerin on coronary collateral function during exercise evaluated by quantitative analysis of thallium-201 single photon emission computed tomography

A noninfarcted, entirely collateral-dependent myocardial region provides an opportunity to assess the effect of nitroglycerin on coronary collateral function during exercise. Stress thallium-201 computed tomography was performed in seven patients with effort angina and no history of myocardial infarction, both before and after nitroglycerin (0.3 mg). All patients had single-vessel disease with total or subtotal (99% with delay) occlusion of proximal left anterior descending coronary artery and well-developed collaterals. The pressure-rate product, mean blood pressure, and heart rate at peak exercise did not differ before and after nitroglycerin. The size of the perfusion defect and the severity of ischemia during exercise estimated by quantitative analysis of thallium-201 single photon emission computed tomography were significantly less after nitroglycerin administration (extent score: 23 +/- 17 vs 7 +/- 9, p less than 0.01; severity score: 20 +/- 22 vs 3 +/- 4, p less than 0.05). The pressure-rate products at peak exercise did not differ before and after nitroglycerin, which suggested that the reduction in perfusion defect size was unlikely to be the result of decreased myocardial oxygen consumption. These results suggest that nitroglycerin improved coronary collateral function during exercise and thus prevented exercise-induced myocardial ischemia.     

Dobutamine stress echocardiography: its role in the diagnosis of coronary artery disease.

We have assessed the usefulness of dobutamine infusion for the diagnosis of coronary artery disease by using two-dimensional echocardiography and 12-lead electrocardiogram. Dobutamine was infused at incremental doses (up to a maximum of 40 micrograms kg-1 min-1) in 52 patients with chest pain; all the patients underwent coronary angiography; significant coronary artery disease was quantitatively defined as greater than or equal to 50% diameter stenosis. Thirty-six patients were on betablockers. The test was considered positive when new regional wall motion abnormalities appeared during dobutamine infusion. No significant side effects occurred in any patient during the test. Transient wall motion abnormalities were detected in 20 of 37 patients with coronary artery disease (sensitivity = 54%); ischaemic ST segment changes were present on ECG in nine patients (sensitivity = 24%). Dobutamine stress echocardiography was negative in 12 of 15 patients with coronary artery diameter stenosis less than 50% (specificity = 80%). Exercise electrocardiography (ECG) was performed in 35 of these 52 patients. Maximum heart rate and systolic blood pressure were significantly higher during exercise than during dobutamine stress test (127 +/- 23 vs 99 +/- 24 beats min-1, P less than 0.0001; 179 +/- 25 vs 152 +/- 30 mmHg, P less than 0.0001). The exercise ECG test was positive in 12 of the 26 patients with significant coronary artery disease (sensitivity = 46%), and dobutamine stress echocardiography in 16 (sensitivity = 62%). Dobutamine stress echocardiography test is a safe and feasible diagnostic test for the noninvasive diagnosis of coronary artery disease and can be performed in patients unable to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial cell membrane stress ionic dyskinesia reversal by diltiazem

Based on previous observations of cardioplegic ionic myocardial distress, myocardial stress dyskinesia was investigated as another possible cause of exercise stress testing-induced silent myocardial ischemia by analyzing the efficacy of the myocytic calcium channel blocker diltiazem in normalizing the results of patients who previously tested positive.From October 2004 to February 2006, 25 patients (13 women [52%]; aged between 28 and 71 years; mean age 56.9 years) complaining of precordial pain, with no coronary artery obstruction detected by scintigraphy and coronary cineangiography studies, presenting with positive ergometric testing, defined by ST segment depression, with no precordial pain or arrhythmia during testing, were treated with diltiazem in three daily doses of 90 mg, and were restudied five or seven days after the first examination. Treadmill electrocardiography exercise testing was performed using the standard Bruce protocol, analyzing the following parameters: the J point and Y point of the ST segment depression, maximum oxygen uptake reached, heart rate, double product and exercise performance measured in metabolic equivalents.The administration of diltiazem abolished patients' complaints of atypical precordial pain in all cases and blocked ST segment depression, both J point (control: mean 2.3+/-0.5 mm; with treatment: 0.4+/-0.5 mm; P<0.001) and Y point (control: mean 1.9+/-0.7 mm; with treatment: 0.1+/-0.3 mm; P<0.001). The heart rate variations were not significant (P>0.05), with mean values of 156.2+/-12.0 beats/min for the control and 149.0+/-19.2 beats/min with treatment. There was significant (P<0.01) improvement in the functional classification of the heart with treatment (mean 2.7+/-0.9 for the control and 2.0+/-0.7 with treatment), without significant variations (P>0.05) in maximum oxygen uptake and double product results.The administration of the myocytic calcium channel blocker diltiazem impeded the occurrence of the silent ST segment depression, previously induced by exercise stress testing in patients without confirmed obstructive coronary artery disease, supporting the involvement of calcium-dependent myocardial contraction ionic dyskinesia in the genesis of silent ST segment depression.     

Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris

To analyze the mechanisms of action of molsidomine, a new antianginal drug, 10 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 1 hour after intravenous administration of 2 mg of molsidomine. When angina pectoris was prevented after the drug was given (6 of 10 patients), the exercise intensity was increased until the recurrence of angina (3 patients) or until exhaustion (3 patients), and hemodynamic data were recorded at this higher exercise capacity. At rest and during submaximal exercise, molsidomine increased heart rate and decreased cardiac output and mean systemic and pulmonary arterial pressures. The prevention of angina pectoris was attended by lower mean systemic and pulmonary arterial pressures and pressure-rate product; cardiac output and heart rate were unchanged. The greater exercise capacity (+26 percent) after molsidomine was attended by increases in maximal cardiac output (+19 percent) and in arteriovenous oxygen difference (+6 percent); the maximal pressure-rate product was unchanged and systemic vascular resistance was lower. The mechanisms of action of molsidomine are very similar to those of nitrates and imply a decrease in venous and arterial tone. Molsidomine deserves further study in patients with angina or congestive heart failure.     

Antianginal effects of corwin, a new beta-adrenoceptor partial agonist

The hemodynamic effects of corwin were evaluated in 9 patients with coronary artery disease and without clinical signs of heart failure at rest, during submaximal exercise and during exercise-induced angina pectoris before and after administration of corwin. Angina pectoris was always prevented after the drug was given and the exercise intensity was increased until recurrence of angina pectoris; hemodynamic data were also recorded at this higher exercise capacity (+16%: p less than 0.001). At rest, corwin increased heart rate (from 80 to 84 beats/min) and pressure-rate product. During submaximal exercise, heart rate decreased from 105 to 96 beats/min, and pressure-rate product and ST-segment depression also decreased after corwin. The prevention of angina pectoris in all patients was accompanied by a lower heart rate (from 132 to 117 beats/min), pressure-rate product and ST-segment depression. At rest and during exercise, the cardiac output was unchanged and the pulmonary capillary wedge pressure was slightly decreased after corwin (from 12.5 to 10 mm Hg; p less than 0.001). At the 16% greater exercise capacity after corwin, angina pectoris recurred at the same values of cardiac output, pulmonary wedge pressure and ST-segment depression; maximal heart rate decreased from 132 to 124 beats/min, and the pressure-rate product was lower. Thus, corwin is an active antianginal drug. Its effects are likely due to a decrease in pressure-rate product and myocardial oxygen requirements during exercise. In contrast to beta-antagonists devoid of partial agonist activity, corwin does not depress left ventricular function either at rest or during exercise.     

Hemodynamics of patients with severe chronic obstructive pulmonary disease during progressive upright exercise

This study evaluated the relationship between the oxygen consumption (VO2) and cardiac output and heart rate during progressive exercise in the upright position in 26 patients with severe chronic obstructive pulmonary disease. Forced expiratory volume in one second (FEV1) was 0.82 +/- 0.21 L, and single-breath carbon monoxide diffusing capacity was 39 +/- 20% predicted. Cardiac outputs were measured by the direct Fick method. The patients as a group had a normal cardiac output for the level of VO2. The mean pulmonary artery pressure in our patients (22.5 +/- 10.1 mmHg) was increased at rest; during exercise, it increased abnormally to 45.5 +/- 18.9 mmHg. The heart rates were increased both at rest and during exercise, and the increase in heart rate for an increase in VO2 was higher than normal. The relative tachycardia observed was probably related to a combination of abnormal arterial blood gases, concomitant bronchodilator administration, deconditioning, and right ventricular dysfunction. The relative tachycardia did not appear to have an adverse effect on exercise tolerance because the ratio of maximal exercise ventilation to the FEV1 exceeded 35 in those patients with observed maximal heart rates above 90% of predicted. The results of this study suggest that improvements in the exercise tolerance of these patients is dependent upon improving their ventilatory capabilities or the efficacy of their ventilation.     

Comparison of chest pain, electrocardiographic changes and thallium-201 scintigraphy during varying exercise intensities in men with stable angina pectoris

This study was performed to evaluate the presence of angina pectoris, electrocardiographic changes and reversible thallium-201 defects resulting from 2 different levels of exercise in 19 patients with known coronary artery disease and evidence of exercise-induced ischemia. The exercise protocols consisted of a symptom-limited incremental exercise test (Bruce protocol) followed within 3 to 14 days by a submaximal, steady-state exercise test performed at 70% of the maximal heart rate achieved during the Bruce protocol. The presence and time of onset of angina and electrocardiographic changes (greater than or equal to 0.1 mV ST-segment depression) as well as oxygen uptake, exercise duration and pressure-rate product were recorded. Thallium-201 (2.5 to 3.0 mCi) was injected during the last minute of exercise during both protocols, and the images were analyzed using both computer-assisted quantitation and visual interpretations. Incremental exercise resulted in anginal symptoms in 84% of patients, and electrocardiographic changes and reversible thallium-201 defects in all patients. In contrast, submaximal exercise produced anginal symptoms in only 26% (p less than 0.01) and electrocardiographic changes in only 47% (p less than 0.05), but resulted in thallium-201 defects in 89% of patients (p = not significant). The locations of the thallium-201 defects, when present, were not different between the 2 exercise protocols. These findings confirm the sequence of the ischemic cascade using 2 levels of exercise and demonstrate that the cascade theory is applicable during varying ischemic intensities in the same patient.     

Hemodynamic and antianginal effects during rest and exercise of intravenous isradipine, a new dihydropyridine calcium antagonist

In an open randomized study, hemodynamic and antianginal effects of nifedipine and the new dihydropyridine derivative isradipine were compared in patients with stable, angiographically confirmed coronary heart disease. Right heart hemodynamics, systemic arterial blood pressure, ECG, and drug plasma concentrations were measured before medication at rest and exercise, after infusions of increasing doses at rest, and again after treatment at rest and exercise. A linear relationship between serum concentrations and cumulated dosages was obtained for both drugs. At rest, both drugs significantly increased cardiac output and heart rate. The reduction of arterial blood pressure was significantly greater after isradipine (systolic from 148 +/- 3 to 104 +/- 3 mmHg; diastolic from 90 +/- 4 to 58 +/- 2 mmHg) than after nifedipine (systolic 149 +/- 6 to 125 +/- 4 mmHg; diastolic 92 +/- 4 to 76 +/- 3 mmHg). The minimal effective plasma level of isradipine regarding blood pressure reduction was estimated at 5 ng/ml (nifedipine: 10-25 ng/ml). During exercise both medications significantly reduced mean pulmonary artery pressure (isradipine: 40 +/- 3 to 20 +/- 1 mmHg, nifedipine: 37 +/- 4 to 22 +/- 1 mmHg), pulmonary artery wedge pressure (isradipine: 23 +/- 3 to 10 +/- 1 mmHg, nifedipine 24 +/- 3 to 14 +/- 1 mmHg), and diastolic arterial pressure (isradipine: 103 +/- 3 to 73 +/- 4 mmHg, nifedipine: 99 +/- 3 to 91 +/- 2 mmHg), whereas systolic pressure was reduced by only isradipine (189 +/- 4 to 147 +/- 5 mmHg). Neither medication significantly changed electrocardiographic ST depression during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of left ventricular function and severity of coronary artery disease on exercise-induced pulmonary thallium-201 uptake

Pulmonary uptake of thallium-201 during exercise was measured in 58 patients with coronary artery disease and compared with the results from 21 patients with normal coronary arteries and 5 normal volunteers. A quantitative method was used to assess the pulmonary thallium uptake relative to cardiac activity (heart/lung ratio). This ratio was calculated for exercise and for redistribution imaging. The mean exercise heart/lung ratio for the group with coronary artery disease was 1.43 +/- 0.36 SD (n = 58); and for the "normal" group was 2.76 +/- 0.41 (n = 26) (P less than 0.001). Increased pulmonary uptake after exercise in the coronary disease group was reversible (mean redistribution heart/lung = 1.96 +/- 0.37 SD; P less than 0.001). The exercise heart/lung ratio differed significantly between groups with single-, two- and three-vessel disease; patients with and without prior infarction; and patients with exercise-induced ST segment depression and elevation. Linear regression analysis between ejection fraction calculated from equilibrium radionuclide angiography at rest and the exercise heart/lung ratio in the coronary artery disease group gave the equation: exercise heart/lung = 0.857 +/- 0.014 ejection fraction for n = 58; r = 0.695; P less than 0.001. It would appear that the exercise heart/lung ratio is a simple and valuable non-invasive index which should be used as part of routine thallium scan interpretation to provide additional information on left ventricular function after exercise and as an indicator of the severity of obstructive coronary artery disease.     

Effects of pharmacologically-induced hypertension on myocardial ischemia and coronary hemodynamics in patients with fixed coronary obstruction

Twenty patients with fixed coronary artery obstruction were studied during rapid atrial pacing and methoxamine infusion. During pacing to heart rates of 142 +/- 4 (mean +/- SEM) beats per minute coronary sinus flow increased from 108 +/- 8 to 187 +/- 15 cc/min and myocardial oxygen consumption increased by + 80 +/- 11%. During methoxamine infusion that raised arterial systolic pressure to 196 +/- 5 mm Hg, similar increases in coronary sinus flow (to 179 +/- 13 cc/min) and myocardial oxygen consumption (+ 77 +/- 12%) occurred. Chest pain and ischemic ST segment changes developed in 17 and 14 patients respectively during atrial pacing, an incidence significantly greater (P less than 0.05) than during infusion of methoxamine (6 and 3 patients). Myocardial lactate extraction which averaged 26 +/- 4% during control was decreased to 10 +/- 8% during pacing and to 24 +/- 7% during methoxamine; the difference between decreases was not significant. The data show that at similar increases in myocardial oxygen consumption stress of increased heart rate results in more myocardial ischemia than stress of increased afterload.     

Effects of diltiazem during tachycardia-induced angina pectoris

To investigate the mechanism of relief of angina pectoris by diltiazem administration, 14 patients with effort angina were studied using a protocol to control heart rate. Coronary, systemic and left ventricular (LV) hemodynamic function was assessed at rest and during tachycardia stress (atrial pacing)-induced angina before and during diltiazem infusion. Angina occurred in all patients during tachycardia stress before diltiazem administration. During tachycardia stress at the heart rate that produced angina after diltiazem infusion, pressure-rate product, coronary sinus flow and resistance and ST-segment depression were all similar to findings before diltiazem. Although at the onset of angina, systolic pressure was usually slightly lower after diltiazem infusion (138 +/- 11 vs 128 +/- 11 mm Hg, p less than 0.05), the pacing rate at onset of angina was higher in only 3 patients and the pressure-rate product was higher in only 1 patient. After diltiazem, left ventricular end-diastolic pressure increased less frequently after interruption of pacing. The results suggest that diltiazem favorably alters the relation between myocardial oxygen demand and supply at rest, but during tachycardia, anginal threshold and coronary reserve do not change. Diltiazem's potent antianginal action, shown in previous investigations using exercise-induced angina, is not prominent when heart rate is controlled. The major benefit of diltiazem in patients with stress-induced angina is related to reduction of myocardial oxygen demand rather than improved myocardial oxygen delivery.     

Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with chronic obstructive pulmonary disease. A controlled double-blind study

To determine whether nifedipine reduces pulmonary artery pressure and pulmonary vascular resistance index during rest and exercise in patients with hypoxic pulmonary hypertension, we studied 6 clinically stable patients using a randomized, double-blind, crossover design. While patients were hypoxic, nifedipine significantly lowered mean pulmonary artery pressure during rest from (mean +/- SEM) 38 +/- 2 mmHg with placebo to 35 +/- 3 mmHg with nifedipine (p less than 0.01) and during exercise from 63 +/- 4 mmHg with placebo to 51 +/- 3 with nifedipine (p less than 0.01). During hypoxia nifedipine reduced pulmonary vascular resistance index during rest by 27% from 7.84 +/- 0.5 units with placebo to 5.71 +/- 0.6 units with nifedipine (p less than 0.02) and during exercise by 44% from 7.84 +/- 1 units with placebo to 4.37 +/- 1 units with nifedipine (p less than 0.001). Nifedipine when added to low flow oxygen reduced pulmonary vascular resistance index during rest by 16% from 6.15 +/- 0.8 units with oxygen to 5.14 +/- 0.5 units with oxygen plus nifedipine (p less than 0.007) and during exercise by 27% from 5.9 +/- 0.9 units with oxygen to 4.3 +/- 0.7 units with oxygen plus nifedipine (p less than 0.005). On room air nifedipine decreased PaO2 during rest by only 4 +/- 1 mmHg and did not decrease exercise PaO2. During oxygen therapy nifedipine decreased PaO2 during rest by 12 +/- 4 mmHg and during exercise by 8 +/- 3 mmHg. Nifedipine therapy, however, substantially increased oxygen delivery during rest and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient left ventricular dysfunction during provocative mental stress in patients with coronary artery disease

We studied the temporal effects of various types of mental stress and physical exercise on the left ventricular ejection fraction (LVEF) in seven normal volunteers and nine patients with coronary artery disease. Three types of psychological stress were administered: mental arithmetic, the Stroop color word test, and a personally relevant speaking task. In the normal volunteers the LVEF response was either flat or increased (p less than 0.05) compared to the baseline value during the mental tasks and increased by a mean of 10 +/- 5% (p less than 0.05) during exercise. In contrast, in patients with coronary disease in whom LVEF did not increase greater than or equal to 5% during exercise, LVEF decreased significantly during the mental tasks (p less than 0.05 for arithmetic and Stroop tasks). Typically LVEF decreased quickly during mental stress with an immediate rebound after intervention. Decreases in LVEF during mental stress occurred without chest pain and were not associated with ECG changes. In patients with coronary disease in whom LVEF increased normally with exercise (LVEF increase greater than or equal to 5%), no significant changes in LVEF occurred during mental stress. The heart rate x systolic blood pressure double product during mental stress was significantly less than that achieved during exercise (p less than 0.05) in each normal subject and patient. Thus psychological stress can provoke acute decreases in LVEF in patients with coronary disease and exercise-inducible dysfunction. The silent nature of the mental stress-induced abnormalities and their occurrence at a lower physiologic workload compared to abnormalities during exercise parallel characteristics of transient ischemia noted during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X.

The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of increases in heart rate in determining the occurrence and frequency of myocardial ischemia during daily life in patients with stable coronary artery disease.

OBJECTIVES. The goal of this study was to investigate the role of increases in heart rate in the development of ischemic episodes recorded during ambulatory electrocardiographic (ECG) monitoring in patients with stable coronary artery disease and to establish the importance of such increases in determining the frequency of ambulatory myocardial ischemia. BACKGROUND. The factors that determine the occurrence and frequency of episodes of myocardial ischemia that patients with stable coronary artery disease experience during daily life have not been clearly defined. In particular, the role of increases in heart rate in the development of myocardial ischemia is controversial. METHODS. To address these issues, 54 patients (42 men and 12 women, mean age 60.5 +/- 8 years) with proved coronary artery disease who had > or = 1 mm ST segment depression during exercise testing underwent an exercise treadmill test with use of the National Institutes of Health combined protocol and a 48-h period of ambulatory ECG monitoring. The exercise ischemic threshold was determined as the heart rate at the onset of ST segment depression during exercise testing. RESULTS. During monitoring, 48 (89%) of the 54 patients had at least one episode of ST segment depression (mean +/- SD 6.6 +/- 5 episodes, range 0 to 22). The majority (320 of 359 or 89%) of ischemic episodes were preceded by an increase in heart rate > or = 10 beats/min; the most significant increase (22.3 +/- 10 beats/min) occurred during the 5-min period before the onset of the episode. An ischemic episode occurred 80% of the times the heart rate reached the exercise ischemic threshold. A strong correlation was observed between the number of times the exercise ischemic threshold was reached during monitoring and both the number and the duration of ischemic episodes (r = 0.90 and 0.71, respectively, p < 0.0001). CONCLUSIONS. Increases in heart rate that exceed the exercise ischemic threshold are commonly observed before the onset of episodes of ambulatory myocardial ischemia in patients with stable coronary artery disease. Moreover, such increases constitute an important determinant of the frequency of myocardial ischemia during daily life. These findings may explain the variability observed in the number of ischemic episodes and may have important implications for the mechanisms that contribute to myocardial ischemia in daily life and for the clinical evaluation of patients with coronary artery disease.     

Effect of beta-blockade on low heart rate-related ischemia during mental stress.

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.     

Evidence for emotionally-induced coronary arterial spasm in patients with angina pectoris.

Twelve executives with typical angina pectoris, given a 12-minute quiz, designed to be psychologically stressful, responded with ST depressions of greater than or equal to 1.0 mm. Each of these patients was given an exercise tolerance test on an upright bicycle to induce an amount of ST depression equivalent to that observed during the quiz. A statistical analysis was made of the products of the heart rate and the systolic blood pressure (rate-pressure product), at the onset of equivalent ST depression on both tests. At the maximal ST depression during the quiz, the mean rate-pressure product was 181 +/- 64 (SD) X 10(2), and at an equivalent ST depression during exercise it was 225 +/- 54 X 10(2); the mean difference was 44 +/- 40 X 10(2). Inasmuch as the rate-pressure product is an index of myocardial oxygen consumption, the differences in rate-pressure product suggest that myocardial ischaemia occurred at a lower myocardial oxygen consumption during emotional stress than during exercise. If equivalent degrees of ST depression during exercise and the quiz are indicative of equivalent ischaemia, than a relative reduction in coronary blood flow during emotional stress, probably by coronary spasm, may be postulated as the most reasonable explanation for these observations.     

Effects of propafenone on coronary and systemic hemodynamics

This study was undertaken to evaluate the effects of intravenous Propafenone (2 mg/kg over 5') on Left Ventricular (LV) function and coronary blood flow. Twelve patients with coronary artery disease and post-ischemic LV disfunction were examined during routine cardiac catheterization. Serial measurements of central hemodynamics, LV high-fidelity pressure and coronary blood flow were recorded at rest and every 10' after Propafenone administration. Heart rate was unchanged, suggesting that Propafenone did not affect sympathetic tone. Cardiac index slightly decreased (from 3.3 +/- 0.9 L/min/m2 to 3.1 +/- 0.6 L/min/m2 at 10', p = ns), LV end-diastolic pressure rose significantly (from 17.7 +/- 2.1 mmHg to 22.7 +/- 4.2 mmHg at 20', p less than 0.01) and dP/dt max fell from 1897 +/- 291 mmHg/sec to 1577 +/- 312 mmHg/sec (p less than 0.02). Systemic vascular resistances had only minimal changes. Concomitantly, coronary vascular resistances decreased (from 0.77 +/- 0.17 mmHg/ml/min to 0.61 +/- 0.12 mmHg/ml/min, p less than 0.02) and coronary blood flow increased (from 138 +/- 29 ml/min to 172 +/- 21 ml/min, p less than 0.01). No significant difference was noted in myocardial oxygen consumption. No symptoms related to LV failure were observed during the study. In conclusion hemodynamic effects of Propafenone are characterized by moderate LV depression and by coronary artery dilatation, probably due to a calcium blocker-like activity.     

The threshold for myocardial ischemia varies in patients with coronary artery disease depending on the exercise protocol

It is generally accepted that angina pectoris and, presumably, myocardial ischemia occur at a fixed heart rate-systolic blood pressure product in a given patient. This concept of a fixed threshold has recently been challenged. To evaluate the effects of varying exercise intensity on the ischemic threshold, 33 patients with coronary artery disease and provokable myocardial ischemia, documented by thallium-201 myocardial perfusion imaging, underwent two exercise tests 2 to 7 days apart. A symptom-limited incremental treadmill exercise test was followed by a 20 min submaximal treadmill test at an intensity approximating 70% of the peak heart rate attained during the incremental test. During the incremental exercise test, angina pectoris developed in 16 patients and 17 patients were asymptomatic. At least 0.1 mV of ST segment depression developed in all subjects during the incremental exercise test at a mean exercise duration of 5.3 +/- 2.6 min, a rate-pressure product of 19,130 +/- 5,735 and oxygen uptake of 19.6 +/- 7.0 ml/kg per min. During the submaximal exercise test, 28 (85%) of the 33 patients had significant ST segment depression. Of these patients, 24 (86%) were asymptomatic, including 10 patients who had previously reported anginal symptoms during the incremental test. The average time to onset of 0.1 mV ST segment depression during the submaximal test was 8.1 +/- 4.5 min. These changes occurred at a rate-pressure product of 15,250 +/- 3,705 and an oxygen uptake of 14.3 +/- 5.9 ml/kg per min, and were significantly (p less than 0.001) lower than values observed during the graded exercise.(ABSTRACT TRUNCATED AT 250 WORDS)