Bruce Protocol Treadmill Test Research Articles

THE ACUTE EFFECTS OF EXERCISE ON POST-EXERCISE INFLAMMATION AND IRON REGULATION: A COMPARISON BETWEEN TRAINED AND UNTRAINED MEN

This study examined whether the magnitude of the effects of an exercise bout on inflammatory markers and iron regulation in humans differs between trained and untrained men. Changes in cell...

Cardio-pulmonary fitness test by ultra-short heart rate variability

Objectives:It is known that exercise induces cardio-respiratory autonomic modulation. The aim of this study was to assess the cardio-pulmonary fitness by ultra-short heart rate variability.Materials and Methods:Study population was divided into 3 groups: Group-1 (n = 40) consisted of military sports man. Group-2 (n = 40) were healthy age-matched sedentary male subjects with normal body mass index [BMI = 19 - 25 kg/m2). Group-3 (n = 40) were healthy age-matched obese male subjects [BMI > 29 kg/m2). Standard deviation of normal-to-normal QRS intervals (SDNN) was recorded over 15 minutes. Bruce protocol treadmill test was used; and, maximum oxygen consumption (VO2max) was calculated.Results:When the study population was divided into quartiles of SDNN (first quartile: < 60 msec; second quartile: > 60 and < 100 msec; third quartile: > 100 and <140 msec; and fourth quartile: >140 msec), progressive increase was found in VO2max; and, SDNN was significantly linked with estimated VO2max.Conclusion:In conclusion, the results of this study demonstrate that exercise training improves cardio-respiratory autonomic function (and increases heart rate variability). Improvement in cardio-respiratory autonomic function seems to translate into a lower rate of long term mortality. Ultra-short heart rate variability is a simple cardio-pulmonary fitness test which just requires 15 minutes, and involves no exercise such as in the treadmill or cycle test.

Aerobic exercise in children with oxidative phosphorylation defects

Fatigue and exercise intolerance are symptoms in children with metabolic myopathy. Frequently this is combined with muscle pain in children with mitochondrial myopathy. Offering therapeutic advice remains challenging in this patient group. Here we describe five children above the age of four years, with normal intelligence, myopathy, exercise intolerance, motor developmental delay, and fatigue, who were diagnosed with a mitochondrial dysfunction. Based on the positive experience of condition training in adults with mitochondrial disease and inactivity, aerobic exercise training was advised for all the children. Because of the lack of clear protocols for individualized mitochondrial myopathies, regular training was initiated. The Movement Assessment Battery of Children, the Jamar dynamometer for grip force, and the Bruce protocol treadmill test were applied for evaluation. No patient showed significant disease progression on a weekly scheme of strength training or on aerobic training during periods varying between 6 and 18 months. Only one out of the five patients has shown an improvement after a period of structured, aerobic training, demonstrating good compliance and motivation over the course of 18 months. Some patients developed severe muscle pain after explosive exercise. Even in a relatively homogenous, intelligent group of patients and motivated parents, we could not reach full compliance. With our case studies, we would like to draw attention to the importance and pitfalls of movement therapy in children with mitochondrial disease.

Comparison of Myocardial Ischemia on the Ergocycle Versus the Treadmill in Patients With Coronary Heart Disease

We previously observed an attenuation of exercise-induced myocardial ischemia on the ergocycle during a ramp protocol compared to the standard Bruce protocol treadmill test in patients with coronary heart disease. However, it was uncertain whether decreased ischemia on the ergocycle resulted from the warm-up effect of the more gradual ramp protocol or from the mode of exercise itself (cycling vs running). Sixteen stable patients, aged 64 +/- 5 years, with documented coronary heart disease (> or =70% coronary artery stenosis and/or reversible myocardial perfusion defects) performed 3 symptom-limited exercise tests: the standard Bruce protocol treadmill test and 2 individualized ramp protocols (treadmill and ergocycle). We measured the ischemic threshold (heart rate x systolic blood pressure product at 1-mm ST-segment depression) and oxygen consumption (VO(2)). The ischemic threshold was higher during cycling (ergocycle ramp, 24,009 +/- 5,769 beats/min x mm Hg) compared to running (Bruce treadmill, 20,429 +/- 3,508 beats/min x mm Hg; and ramp treadmill, 19,451 +/- 3,392 beats/min x mm Hg; p <0.001), independently of exercise intensity (VO(2)). The peak VO(2) did not significantly differ among all tests (p = 0.25) despite a greater peak rate-pressure product achieved with the ergocycle (29,378 +/- 6,291 beats/min x mm Hg) compared to either treadmill protocol (Bruce, 26,202 +/- 5,831 beats/min x mm Hg; ramp, 25,654 +/- 6,492 beats/min x mm Hg; p <0.001). In conclusion, the mode of exercise (ergocycle vs treadmill), rather than the type of protocol (ramp vs Bruce), is associated with an attenuation of electrocardiographic parameters of myocardial ischemia, independently of exercise intensity (VO(2)) and myocardial demand (rate-pressure product).

Noninvasive Detection of the Hemodynamic Stress of Exercise Using the Photoplethysmogram

Exercise induced hemodynamic stress has been studied extensively using a wide range of physiological sensors. While athletes can modulate their training intensity using EKG-based heart rate monitors, there are currently no noninvasive monitors that can be used to ascertain with a high degree of certainty the hemodynamic stress an individual is experiencing because of fatigue or an underlying pathology. We propose that cardiac stress will result in detectable changes in skin blood flow. In a clinical trial with eleven healthy subjects performing the Bruce Protocol treadmill test low frequency waves were observed in the blood flow to both the forehead and ear, but not the finger, using photople- thysmographs (PPG) measured by a pulse oximeter. As volitional fatigue approached, the low frequency (f = 0.05-0.2 Hz) amplitude modulation observed in the PPG became more pronounced; then, within several seconds of the cessa- tion of the protocol, they disappeared. Using a software-based detector, these distinct waves are reliably detected, with a low incidence of false positives, in all subjects before the onset of volitional fatigue. We hypothesize that the low frequency waves observed in the PPG of individuals exercising to volitional fatigue provide a mechanism for noninvasively detecting hemodynamic stress to the human vascular system.

Cardiovascular Responses to Climbing Mt. Rainier in Relation to Aerobic Fitness and Body Composition

Mountaineering provides considerable challenge to cardiovascular fitness because of vertical climbing, the additional weight of a backpack and the change in partial pressure of oxygen with increasing altitude. Few studies have looked at the relationship between VO2 max and body composition and the cardiovascular responses to high altitude summit climbs. Recent technological advances (heart rate data loggers and GPS) have made this sort of data collection possible. PURPOSE: The purpose of this study was to assess cardiovascular responses while ascending Mt. Rainier in middle age males with varying aerobic fitness and body composition. METHODS: Four middle-aged males volunteered to participate in this study. Aerobic capacity was determined by completing a Bruce protocol treadmill test with metabolic assessment. Body composition was assessed by skinfold thickness using the Jackson and Pollock three-site formula. Aerobic capacity and body composition were determined before attempting the summit climb. Heart rate during the climb was measured using a Polar Heart Rate data logger and elevation was determined using a handheld portable GPS. Climbers ascended from 5,420 feet to 10,030 feet over approximately 6h, during which data were collected. RESULTS: Four males with an age of 49.8 + 4.2y, an aerobic capacity of 44.0 + 8.0 ml.kg.min-1 and % fat of 21.4 + 4.3 completed the study. When assessing the relationship of %HRR to VO2max, an inverse relationship was observed (r= −.86). In addition, when assessing the relationship of %HRR to body fat%, a positive relationship was observed (r= .95). CONCLUSIONS: The results suggest that aerobic fitness has a pronounced effect on exercise intensity when climbing Mt. Rainier. In addition, body fat% demonstrated to have a strong positive influence on oneâЄ™s HR response when climbing Mt. Rainer. These results strongly suggest the need to promote aerobic fitness and decrease body fat when preparing to climb Mt. Rainer successfully.

The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease.

The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD. Thirty individuals from three groups (10 controls, 11 with type 1 VWD and 9 with type 2B VWD) completed the Standard Bruce Protocol Treadmill Test. A bleeding questionnaire was administered and blood tests were performed pre- and immediately postexercise. The groups were well matched for age, gender and body mass index (BMI). There was a correlation in all groups between the metabolic equivalents (METS) achieved and the degree of change of VWF and FVIII:C levels (P < 0.002, Pearson's correlation). There was a significant postexercise increase in VWF:Ag, VWF:RCo, FVIII:C and activated VWF levels in both the control group and in the type 2B VWD group, but not in the type 1 VWD group. Specific to the type 2B VWD group was an increase in the percentage of high molecular weight multimers (P = 0.022), a decrease in the mean platelet count compared with the other groups (P < 0.001) and an increase in the ADAMTS-13 level (P = 0.001). There are significant differences in the effects of exercise on individuals with type 1 and type 2B VWD compared with controls. Further clinical studies are necessary to evaluate exercise as a therapeutic option in VWD.

Evaluation Of Telemetric Heart Rate Monitors During Treadmill Exercise

Measurement of heart rate during exercise is extremely important to the understanding of energy expenditure and physical training of the cardiovascular system. Accurate measurements of heart rate have been encumbered by the size of the monitor, difficulty of use, and the reliability of the measurement devices in the presence of movement artifacts. There is interest in developing accurate, small, non-intrusive monitors for use in exercise regimens where direct wire leads cannot be tolerated, where ease of use is critical, and where movements may give rise to artifacts. PURPOSE This study evaluated three telemetric heart rate monitors, the Actiheart [AH] (Mini Mitter Co., Inc., Bend, OR), Polar #S-810i and XR [PL](Polar, Finland), and XHR VitalSense Heart Rate sensor [VS] (Mini Mitter Co., Inc., Bend, OR). METHODS All heart Rate sensors were compared to the Welch-Allyn Atlas (6200 Series) stationary heart rate monitor. Six (6) volunteers, three men and three women, wore the four sensors, placed in specific locations on the chest. All sensors were attached to 3M Red Dot electrodes in a specific placement to maximize the electrical signal and placement was in a random order so as not to bias the data due to placement alone. Data were recorded as beats per minute in fifteen-second epochs. Subjects rested for ten minutes to determine resting heart rate and then all subjects completed a modified Bruce protocol treadmill test (3 minutes 1.7 mph, 0% slope; 3 minutes 2.5 MPH, 3% Slope; 3 minutes 3.4 MPH, 6%; and 3 minutes 4.2 mph, 9% slope). Following the exercise protocol subjects were allowed to rest until heart rate returned to resting values. RESULTS All three of the devices demonstrated a similar specificity, 0.97, 0.98, 0.97, for AH, PL, and VS respectively. However, PL demonstrated a significantly, p < 0.01, reduced sensitivity (0.85) as compared to AH (0.98) and VS (0.98). In addition, PL also showed a significantly greater number of false positive readings (15.2%) as compared to AH (2.34%) and VS (2.5%). The correlation between PL and the Atlas standard was significantly worse during exercise as compared to rest. CONCLUSION The results reported here indicate that there is a need for additional studies to validate accurate measurements of heart rate in exercising subjects, particularly when the exercise is rigorous. Supported by Mini Mitter, CO., Inc and U.S. Army DAMD17-01-C-0022

Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study.

The value of exercise testing in women has been questioned. To determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years. Near-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995. A total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease. Cardiovascular and all-cause mortality. There were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P =.96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P =.002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001). The prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables.

Changes in QT interval with exercise in elite male rowers and controls

Background: QT interval prolongation occurs at rest and during exercise in pathological left ventricular hypertrophy. However, athletes with physiological hypertrophy have normal QT at rest. The aim of this study was to compare the effect of exercise on QT in athletes with echocardiographic left ventricular hypertrophy and normal controls, and explore differences in their response. Methods: Elite male rowers ( n=15) with echocardiographic left ventricular hypertrophy, and normal volunteers ( n=15) underwent 15 min of a Bruce protocol treadmill test. Electrocardiograms (ECGs) were recorded during each stage and every minute during recovery for 3 min. QT was measured at each stage. Corrected QT (QTc) was calculated using Bazett’s formula. Results: QT at rest was significantly greater than QT after 3 min of recovery in the controls (0.36±0.02 vs. 0.32±0.04 s; P=0.001) but not in the athletes (0.36±0.03 vs. 0.34±0.02 s; P=0.05). Regression lines for QT versus heart rate showed a strongly negative correlation in both athletes and controls ( y=0.463−0.0013 x ( r=0.91; P<0.0001) and y=0.461−0.0013 x ( r=0.93; P<0.0001), respectively), but greater individual homogeneity in the athletes. Conclusions: training-induced hypertrophy does not affect the heart rate/QT relationship. The more rapid recovery in QT and homogeneity of the heart rate/QT relationship in athletes compared to controls is likely to be a benign effect of myocardial fitness, but it is hypothesised that it may contribute to arrhythmias in the unfit individual after vigorous exertion.

Abnormal responses for blood pressure in children and adults with surgically corrected aortic coarctation.

Despite successful surgical repair of aortic coarctation, life expectancy is reduced, and up to one-third of patients remain or become hypertensive. So as to characterize the responses for blood pressure, we have studied 55 patients with surgically repaired coarctation. Their mean age was 11.3 +/- 5.97 years. We documented maximal uptake of oxygen, anaerobic threshold, plasma renin activity and blood pressures during a Bruce protocol treadmill test. The velocity across the site of repair as imaged by cross-sectional echocardiography was measured before and after exercise. We measured the changes in heart rate and blood pressure subsequent to an infusion of 1 ug per kg of isoprenalin, monitoring blood pressure over 24 hours in all patients. When compared with 40 healthy age-matched controls, the patients with coarctation had a normal exercise capacity. Resting systolic blood pressures above the 95th percentile were present in 45% of the patients. Exercise-induced hypertension, and an elevation in the average systolic 24 hour blood pressures, were observed, but less frequently than elevated baseline values, suggesting that so-called white-coat" hypertension may be present in this population. Abnormal reactions and elevation of plasma renin activity were related to a history of paradoxical hypertension at the time of surgery. Attenuation of the circadian rhythm for blood pressure was a frequent finding, and may have implications in the development of long-term damage to end-organs. A high correlation was found between mean systolic blood pressure measured by 24 hour monitoring and left ventricular hypertrophy (r=0.65, p<0.05). Abnormalities in blood pressure occurred independently of significant mechanical obstruction. Despite successful surgical repair, abnormalities in the shape of the aortic arch, reduced sensitivity of baroreceptor reflexes, and neurohumoral factors may all contribute to the development of hypertension.

Exercise-induced ventricular arrhythmias in patients with healed myocardial infarction

Background: Controversy exists about the clinical and prognostic significance of exercise-induced ventricular arrhythmias late after myocardial infarction. The aim of the study was to identify the main clinical and prognostic features of exercise-induced ventricular arrhythmias in out-patients with healed Q-wave myocardial infarction. Methods: The study population was 777 consecutive patients who underwent a symptom-limited (Bruce protocol) treadmill test from May 1988 to January 1991 after myocardial infarction (at least 1 year). Clinical and exercise data were prospectively entered in a computerized database and retrospectively two different groups were selected: (1) 228 patients with exercise-induced ventricular arrhythmias; (2) 549 patients without. Incidence and morphology of exercise-induced ventricular arrhythmias, various exercise parameters and a follow-up were evaluated. Results: Patients with exercise-induced ventricular arrhythmias were older ( P < 0.001), had higher blood pressure ( P < 0.03) and peak exercise rate pressure product ( P < 0.00) than the others. No difference was found in the incidence of exercise-ischaemia: either symptomatic or not. When simple (≤2 Lown) versus complex (≥3 Lown) exercise-induced ventricular arrhythmias were considered, the latter were more frequent in patients with anterior myocardial infarction, shorter exercise duration ( P < 0.001) and lower exercise rate pressure product, lower ejection fraction and lower incidence of exercise-induced ischaemia. In the follow-up (mean 24 ± 13 month) there were 24 deaths: five (2.2%) in patients with exercise-induced ventricular arrhythmias and 19 (3.4%) in patients without. Cardiac event rate was similar in both groups. Conclusions: We conclude that in out-patients with healed myocardial infarction exercise-induced ventricular arrhythmias are quite frequent, but they are not associated with exercise-induced ischaemia, either symptomatic or not. Exercise-induced ventricular arrhythmias seem to be related to age or peak workload. Moreover patients with these arrhythmias have no adjunctive negative risk on prognosis.

Spectrum of hypertensive heart disease in Nigerians: cross-sectional study of echocardiographic indices and their correlation with treadmill exercise capacity

The aims of this study were to provide cross-sectional data on echocardiography in Nigerians with normotension, essential hypertension and hypertensive heart failure, and to correlate the echocardiographic indices with treadmill functional capacity. M-mode and two-dimensional echocardiography and a Bruce protocol treadmill test were undertaken in Nigerians with essential hypertension (n = 22) and hypertensive heart failure (n = 12), and in matched healthy volunteers (n = 15). A striking echocardiographic feature was the tendency to eccentric or asymmetric left ventricular hypertrophy in Nigerians. The septum to posterior wall ratios were 1.4 +/- 0.1 in the normotensives, 1.6 +/- 0.1 in the hypertensives and 1.5 +/- 0.1 in the heart failure group. There was a progressive increase in left ventricular mass index and a reduction in fractional fibre shortening in the hypertensive spectrum. Treadmill exercise capacity also showed a progressive fall from normotensives through hypertensives to the heart failure group. A significant positive correlation was found between fractional fibre shortening and treadmill time in the heart failure group. In Nigerians with hypertensive heart disease, there was a striking tendency for eccentric (asymmetric) rather than concentric left ventricular hypertrophy. Systolic left ventricular contractility may be predictive of treadmill exercise capacity in hypertensives.

Long‐Term Pacing in Heart Transplant Recipients is Usually Unnecessary

The indications for and timing of permanent pacing were reviewed in all 17 of 154 adult heart transplant recipients at this center who have had permanent pacemakers implanted. Resting 12-lead ECGs recorded during routine follow-up were examined. A prospective study of pacing requirement was then undertaken. Holter monitoring was performed before and after reprogramming the pacemakers to VVI mode at 50 beats/min. Exercise responses in various pacing modes were then assessed in seven patients with rate responsive pacemakers using a standard Bruce protocol treadmill test. The indication for pacing was sinus node dysfunction in 59% (10/17) and atrioventricular (AV) block in 41% (7/17). The majority of pacemakers were implanted between seven and 21 days after transplantation. There was a progressive reduction in the frequency of pacing on 12-lead ECGs with time after transplantation. There was a progressive reduction in the frequency of pacing on 12-lead ECGs with time after transplantation. Eight of 14 patients with empirically selected programming paced during Holter monitoring. After reprogramming to 50 beats/min VVI mode only three of 14 patients, all with sinus node dysfunction, paced. Rate responsive pacing made no difference to exercise time. The requirement for long-term pacing in cardiac transplant recipients is small (3/154) and is limited to patients with sinus node dysfunction. Rate responsive pacing did not increase exercise tolerance.

Clinical correlates and prognostic significance of type A behavior and silent myocardial ischemia on the treadmill

Type A patients with coronary artery disease (CAD) tend to ignore or underreport symptoms, especially during challenging tasks such as the treadmill exercise test. To determine whether type A CAD patients might be more likely than type B patients to have silent ischemia during exercise and consequently a worse prognosis, 403 patients with stable CAD who had significant coronary disease on angiography, a positive Bruce protocol treadmill test and a structured interview to assess type A behavior were studied. Median follow-up time was 6 years. Type A patients were more likely to experience silent ischemia during exercise than were type B patients (35 vs 25%, p = 0.05). Patients with silent ischemia during exercise had a history of fewer anginal episodes/week, and type A patients with silent ischemia were less likely to have had a history of typical angina. However, using the Cox model, there were no significant differences in survival between type A patients and B patients with silent ischemia (4-year survival 86 vs 79%, p = 0.44) and no significant differences in survival between type A patients with silent ischemia and type A patients with symptomatic ischemia (6-year survival 86 vs 80%, p = 0.59). Similar results were obtained for infarction-free survival. Type A patients are more likely than type B patients to have silent ischemia during exercise, but long-term survival is not affected.

Plasma beta-endorphin levels in silent myocardial ischemia induced by exercise

Although silent myocardial ischemia is a well recognized phenomenon, the reasons for the lack of symptoms in patients with coronary artery disease (CAD) is unclear. Because the endogenous opioid β-endorphin has been related to pain modulation, plasma β-endorphin levels were studied before, during and after exercise-induced ischemia in symptomatic and asymptomatic men. Because β-endorphin responses have been closely linked to adrenocorticotropic hormone (ACTH) and cortisol responses, these hormones also were measured. Nine symptomatic and 12 asymptomatic patients with a high probability (at least 95%) of CAD and 8 apparently healthy men completed a Bruce protocol treadmill test. Blood samples were drawn before, during and 10 minutes after exercise. During exercise the measured hormones showed no significant increases from basal levels. However, plasma β-endorphin, ACTH and cortisol levels were significantly elevated (p ≤0.01) 10 minutes after exercise in all 3 groups. There was no significant difference in plasma β-endorphin levels curing or after exercise between the symptomatic and asymptomatic patients with CAD. Thus, differences in circulating levels of β-endorphin, ACTH and cortisol are not associated with the presence or absence of pain during exercise-induced myocardial ischemia.

Myocardial ischemia during daily activities and stress

Twenty-four-hour, 2-channel Holter monitoring during daily activities was performed in 210 patients; during the same day a Bruce protocol treadmill test was also performed and the electrocardiogram was recorded using the same Holter system. Significant ST-segment depression was observed during daily activities in 97 patients, while similar changes were recorded during the treadmill test in 122 patients. Thus, 77% of patients with ST depression during the provocation of the treadmill test had ischemic episodes during their everyday life. On the other hand, 3 patients with proven significant coronary artery disease had spontaneous ischemic episodes during daily activities, but had a negative stress test. The ischemic changes during daily activity developed at a lower heart rate than during stress testing (94 beats/ min vs 109 beats/min, respectively, p < 0.05). A total of 351 ischemic episodes were recorded during daily activities, 241 (69%) of these were asymptomatic. In 46 patients all episodes were asymptomatic, in 15 all were symptomatic, while in 36 both symptomatic and silent episodes were detected. The mean duration of the symptomatic episodes was 13.7 minutes and that of the asymptomatic ones was 14.9 minutes (difference not significant). The degree of ST depression in these 2 groups was also similar. Because of more advanced symptomatology in 143 patients, coronary arteriography was performed; 43 had normal and 100 had pathologic coronary arteries. In this selected group, the sensitivity of Holter monitoring during daily activity was 87% and during stress 97%; the specificity during daily activity was 95% and during stress 88%. These data support the use of Holter monitoring for evaluating ischemic changes during daily activity and suggest its potential application for judging efficacy of antianginal therapy.

Comparison of Nadolol, A New Long-Acting Beta-Receptor Blocking Agent, and Placebo in the Treatment of Stable Angina Pectoris

Nadolol, a new nonselective beta 1 and beta 2 adrenergic blocking agent, has a plasma half-life of 17 to 23 hours. We studied 37 volunteers with stable angina pectoris who had five or more episodes of pain per week and who also had a 1 mm or greater ST segment depression 80 msec past the J point during a Bruce protocol treadmill test. An eight-week placebo controlled run-in period preceded double-blind randomization to nadolol administered once per day (17 patients) or identical appearing placebo for four weeks (20 patients), after which an exercise test was done. Diaries for pain episodes and nitroglycerin consumption were kept. Exercise tests were performed 24 hours after the last nadolol or placebo dose. Episodes of pain per week were reduced 59.8 percent after nadolol and 28.2 percent after placebo (P less than .01). Nitroglycerin consumption after nadolol was reduced 66.8 percent while after placebo it was reduced 36.2 percent (P less than .05). Resting and peak heart rates and peak rate-pressure products showed typical reductions due to beta-blockade 24 hours after nadolol compared with stability of these during placebo, all P less than .001. Exercise time after nadolol increased 42.2 percent, which was more than the 14.5 percent increase after placebo (P less than .05). Exercise work after nadolol increased 64.7 percent, greater than the 22 percent increase after placebo (P less than .05). Mean ST segment depression at end of exercise was little changed before and after treatment in both groups, reflecting consistency of effort. Improvement in symptoms and work capacity associated with nadolol significantly exceeded the placebo group responses. Unlike other available agents of this class, a single daily dose of nadolol produced therapeutically effective 24-hour beta-blockade in patients with disabling angina pectoris.