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[Mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery for severe emphysema].

To investigate the mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery (LVRS) for severe emphysema, we performed six-minute walk tests and pulmonary-function tests, and studied their correlation before and 3-to-5 months after LVRS in 7 patients with severe emphysema who underwent bilateral lung reduction via median sternotomy. Results of the tests showed a 59% increase in the 1-second forced expiratory volume (FEV1), a 25% reduction in the functional residual capacity (FRC), a 49% increase in the maximum voluntary ventilation (MVV), and a 20% increase in the distance walked in 6 minutes (6 MD). The degree of improvement in 6 MD correlated significantly with the degree of improvement in FEV1 (r = 0.97, p < 0.01), in FRC (r = 0.86, p < 0.05), and in MVV (r = 0.87, p < 0.05), and did not correlate with the degree of improvement in pulmonary gas exchange. These results support the hypothesis that an increase in lung elastic recoil after targeted emphysematous resection reduces airflow limitation, and thus leads to a short-term improvement in exercise tolerance after LVRS.

Aged↗

Effect of a calcium inhibitor, nifedipine, on exercise tolerance in patients with angina pectoris: a double-blind study.

The effect of nifedipine on exercise tolerance was studied in 30 patients with stable angina and positive graded exercise testing. Treadmill exercise testing was performed on each of five consecutive days. Placebo or nifedipine, 10 mg sublingually, was given 30 minutes before exercise on the third day. The following day the intervention was reversed in a double-blind manner. Angina was abolished by nifedipine but not by placebo in 12 patients (40 percent). The time to onset of angina in the remaining patients increased from 4.1 +/- 0.4 (SEM) to 6.7 +/- 0.6 min (p less than .001). Time to ST depression greater than or equal to 2 mm increased from 4.0 +/- 0.3 to 5.4 +/- 0.5 min, while duration of exercise increased from 6.3 +/- 0.3 to 8.2 +/- 0.4 min (p less than .001). The maximum heart rate was 145 +/- 3.3 with nifedipine and 122 +/- 3.8 min-1 with placebo (p less than .01). Resting systolic blood pressure decreased 30 min after nifedipine administration from 131 +/- 3.4 to 106 +/- 2.9 mm Hg (p less than .01). Maximal systolic blood pressure during exercise was lower with nifedipine (127 +/- 4.8 mm Hg) than with placebo (155 +/- 5.6 mm Hg, p less than .01). We conclude that nifedipine significantly improves the exercise tolerance of patients with stable angina pectoris by decreasing peripheral vascular resistance and myocardial oxygen demand.

Adult↗

Coronary artery calcium, exercise tolerance, and CHD events in asymptomatic men.

Coronary artery calcium (CAC) scores >/=100 are predictive of CHD events in asymptomatic men. Exercise tolerance of >/=10METs predicts lower event rates in CHD patients; however, its relationship with events in individuals with subclinical atherosclerosis is less known. Participants were 710 asymptomatic men from the Aerobics Center Longitudinal Study whose exercise tolerance (ET) was quantified (<10 or >/=10METs) and whose CAC score was >/=100 as measured by electron beam tomography. During 3.5 years of follow-up 59 CHD events occurred. The age-adjusted hazard ratio (HR) of CHD events was 0.26 (95% CI=0.15-0.45) in men whose ET was >/=10METs compared with men whose ET was <10METs. Adjustment for CHD risk factors and abnormal exercise ECG did not change the association between ET and CHD. The extent of underlying atherosclerosis did not influence the association between ET and CHD; for example, the HR for CHD events in the >/=10MET group among men with CAC scores <400 and >/=400 was 0.16 (95% CI=0.05-0.56) and 0.23 (95% CI=0.11-0.46), respectively. In asymptomatic men with subclinical coronary atherosclerosis, an ET of >/=10METs identifies patients at lower risk for manifest CHD.

Calcium↗

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

AIM: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET). METHODS: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET. RESULTS: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all). CONCLUSIONS: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Exercise Therapy↗

Relationship between the chest radiograph, regional lung function studies, exercise tolerance, and clinical condition in cystic fibrosis.

This study evaluated the accuracy of the interpretation of the chest film in delineating localised abnormalities of ventilation and perfusion, as well as the overall severity of airways obstruction, exercise tolerance, and clinical condition in children with cystic fibrosis. Radiographic findings in various regions of the chest film were compared with the functional values obtained with regional lung function tests which evaluated the arrival and disappearance of boluses of radioactive nitrogen given by inhalation and infusion. While the more severely affected areas on the chest radiograph were found to correlate with similar regions on the lung function tests, as did overall scores, errors occurred in some cases if the x-ray film alone was used as a judge of regional physiological derangement. In addition the degree of airways obstruction, the exercise tolerance on a cycle ergometer, and clinical grading, each correlated significantly with the radiographic score. We conclude that the chest radiograph is a good indicator of the overall severity of the lung disease and that it correlates well with exercise tolerance and clinical condition in cystic fibrosis.

Adolescent↗

[Effect of metoprolol on the exercise tolerance in patients with stable angina pectoris (author's transl)].

The effect on the exercise tolerance induced by a new selective beta1-receptor antagonist, metoprolol, given by a single administration per os, has been evaluated in 16 patients with stable angina pectoris. The study was a double blind cross-over between metoprolol 100 mg and placebo. Patients were hospitalized for the time required for the performance of the study; every cardioactive drug, except for trinitrine, was stopped 72 hours prior to the study period. Exercise testing was performed two hours after the intake of the drug, in a sitting position on a bicycle ergometer; the workload was increased by 25 Watts increments every two minutes. Compared to placebo, the total workload performed and duration of exercise increased after metoprolol (P less than 0.001), heart rate decreased (P less than 0.001) both in the resting state and during exercise test, systolic blood pressure didn't change in the resting state but decreased during exercise test (P less than 0.01), pressure-rate product, an useful index of changes in myocardial oxygen consumption decreased both in the resting state (P less than 0.001) and during exercise test (P less than 0.001). It is concluded that metoprolol induces a significant increase in exercise tolerance. This is due to a marked reduction in oxygen myocardial consumption resulting by both decreased heart rate and systolic pressure.

Adult↗

Effect of garlic (Allium sativum) oil on exercise tolerance in patients with coronary artery disease.

The effect of six weeks garlic oil administration was observed on cardiac performance and exercise tolerance in 30 patients of coronary artery disease. After initial treadmill stress test, they were administered garlic oil in the dose of four capsules twice a day for 6 weeks and treadmill stress test was repeated. Garlic significantly (P<0.01) reduced heart rate at peak exercise and also significantly reduced the work load upon the heart resulting in better exercise tolerance (P<0.05) as compared to the initial test. It appears to be a good adaptogen to be utilized in patients with coronary artery disease.

Blood Pressure↗

Myocardial perfusion, function and exercise tolerance after the arterial switch operation.

OBJECTIVES: This study was conducted to determine the prevalence of myocardial perfusion abnormalities at rest and exercise and to assess exercise capacity in children after the arterial switch operation. BACKGROUND: There have been sporadic reports of myocardial ischemia or sudden death in children after the arterial switch operation for transposition of the great arteries, possibly related to inadequate coronary perfusion due to kinking or stenosis of the translocated coronary arteries. METHODS: Myocardial perfusion at rest and peak exercise was assessed using the scintigraphic agent technetium-99m methoxyisobutyl isonitrile (sestamibi). Exercise capacity was determined with a modified Bruce protocol. Ambulatory electrocardiographic (ECG) Holter monitoring was performed. Ventricular function, contractility and wall motion were assessed echocardiographically. RESULTS: Twenty-three children (aged 4.2 to 7.9 years) underwent evaluation. Abnormalities were found on the rest perfusion scans in 22 children (95.6%). The left ventricular myocardium was divided into 13 segments for analysis. Of 299 rest segments, 225 (75.3%) were normal, 11 (3.7%) showed mild defects, 45 (15%) moderate defects and 18 (6%) severe defects at rest. At peak exercise, 237 segments (79.3%) were normal, 24 (8%) showed mild defects, 33 (11%) moderate defects and 5 (1.7%) severe defects. Compared with rest studies, myocardial perfusion grade at exercise was unchanged in 246 segments (82.3%), improved in 42 (14%) and worsened in 11 (3.7%). All patients had normal exercise tolerance without symptoms or ischemic ECG changes. No ventricular tachycardia was seen on Holter monitoring. All patients had a shortening fraction > or = 27%. Left ventricular contractility was normal in 12 children in whom it was assessed. Regional wall motion was normal in 17 children with adequate echocardiographic images for this analysis. CONCLUSIONS: Myocardial perfusion scan abnormalities assessed by technetium-99m sestamibi are common after an arterial switch operation. These abnormalities are of uncertain clinical significance and generally lessen with exercise. The normal exercise tolerance without symptoms or ECG changes suggests that myocardial perfusion is adequate during the physiologic stress of exercise in children up to 8 years after an arterial switch operation.

Child, Preschool↗

Effects of once-daily benazepril therapy on exercise tolerance and manifestations of chronic congestive heart failure. The Benazepril Heart Failure Study Group.

The effects of the long-acting angiotensin-converting enzyme inhibitor benazepril hydrochloride on exercise tolerance and signs and symptoms of congestive heart failure (CHF) were evaluated in a double-blind, multicenter, placebo-controlled clinical trial. Patients with chronic New York Heart Association class II to IV symptoms of CHF and an ejection fraction by radionuclide scanning of less than or equal to 35% were randomized in a 2:1 ratio to treatment with ascending doses of oral benazepril (n = 114) or placebo (n = 58) once daily, while continuing to receive background therapy with digoxin and diuretics. After randomization, patients were evaluated clinically every 2 weeks during a 12-week, double-blind treatment period. Maximal exercise tolerance was measured before and at specified time points after randomization by graded treadmill exercise testing. At week 12, mean exercise time increased 95 +/- 12 (SEM) seconds in the group receiving benazepril, whereas the increase was 37 +/- 18 seconds in the group receiving placebo (p less than 0.01 for the difference between the groups). There was also greater improvement in overall clinical status and in the signs and symptoms of CHF in benazepril-treated patients than in control subjects. There were 3 deaths in placebo-treated patients and none in benazepril-treated patients (p less than 0.05); the overall incidence of adverse effects was identical in the 2 groups. Benazepril is a well-tolerated angiotensin-converting enzyme inhibitor that provides clinically important improvement in exercise tolerance and in signs and symptoms when given once daily to patients with CHF receiving background therapy with digoxin and a diuretic.

Adult↗

Assessing exercise tolerance: a review.

The purpose of this article is to provide guidelines for monitoring and assessing exercise tolerance. Monitoring and interpreting pulse rate, blood pressure, respiration, skin characteristics, fatigue, pain, coordination, and electrocardiography are discussed. The basis for applying these principles to graded-exercise-tolerance testing is also discussed.

Adult↗

The effects of cigarette smoking on cardiopulmonary function and exercise tolerance in teenagers.

Teenagers who smoke are frequently warned that cigarette smoking will have detrimental effects on the function of their cardiopulmonary system and on their ability to perform exercise. However, there is little published evidence to support this statement. Therefore, in the present study, peak expiratory flow was measured as an indicator of lung function, expired carbon monoxide level was measured as an indicator of current smoking and the associated reduction in the oxygen carrying capacity of the blood, and blood pressure and heart rate were measured as indicators of cardiovascular hemodynamics before and after a one-mile run in 27 teenagers. The results show that, even at a young age, cigarette smoking is associated with significant detrimental effects on cardiopulmonary function and exercise tolerance. Objective evidence of an effect of smoking on cardiopulmonary function and exercise tolerance in this age group may assist educators and health care professionals in convincing teenagers to quit smoking.

Adolescent↗

Exercise tolerance is lower in type I diabetics compared with normal young men.

The present investigation was conducted to study metabolic and hormonal responses to prolonged exercise to exhaustion in insulin-dependent diabetic subjects. Sixteen healthy subjects (control) and 15 diabetics with no-insulin administration for 12 hours were studied. They were submitted to short-term exercise to exhaustion on a cycle ergometer at 55% to 60% of maximum oxygen consumption (VO2max). Exercise tolerance was significantly lower in diabetic subjects (66 +/- 6.7 v 117 +/- 9.4 minutes), and glucose concentration was significantly higher in these subjects. At exhaustion, only diabetic subjects showed a significant decrease in glycemia (142 +/- 20 v 111 +/- 16 mg/dL). Lactate concentration increased significantly during exercise up to 30 minutes, but at exhaustion only control subjects showed a reduction. No significant difference in free fatty acid (FFA) concentrations was observed between the groups during a 30-minute exercise period; however, at exhaustion levels were significantly higher in control subjects. Prolactin and C-peptide concentrations were significantly lower in diabetic subjects, whereas glucagon concentration was higher. No significant differences between the groups were observed for cortisol and growth hormone (GH) concentrations. We conclude that (1) diabetic subjects show reduced exercise tolerance when no insulin is administered for 12 hours, and (2) exercise to exhaustion reduces serum glucose concentrations in insulin-dependent diabetics.

Adult↗

Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.

BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease (COPD). However, appropriately controlled studies have not previously been performed, nor have the benefits of different types of continuation programme for rehabilitation been investigated. Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty six patients with severe airways obstruction (mean SD) forced expiratory volume in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC) 37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner. During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11 patients (group A) received a session of physiotherapy once weekly while 12 patients (group B) received a session of physiotherapy once a month. The control group C (13 patients) received no rehabilitation at all. Quality of life was assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six minute walking distance, and lung function by FEV1 and IVC. Outcome measures were assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term improvements in quality of life were found in patients in groups A and B, but not in those in group C compared with baseline, but these only reached significance in group B at all time points. Patients in group B had a higher quality of life than those in group C only at three and 12 months. There was a decrease in both six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18 months) in patients in group C compared with the baseline measurement. Between groups analysis showed no differences for six minute walking distance, FEV1, and IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months. The change in quality of life was not associated with a change in exercise tolerance.

Exercise Tolerance↗

Exercise tolerance in heart transplant patients with altered pulmonary diffusion capacity.

To test whether orthotopic heart transplant (OHT) patients with low pulmonary diffusion capacity have a greater limitation to exercise than OHT patients with normal pulmonary diffusion capacity, we investigated cardiorespiratory responses and blood gases in two groups of OHT patients, one with low (LdG) and the other with normal pulmonary diffusion capacity (NdG), during a graded exercise test. The results showed 1) significantly reduced peak power (P < 0.05), peak oxygen uptake (VO2, P < 0.001), peak oxygen pulse (VO2/heart rate, P < 0.01), peak minute ventilation (VE, P < 0.05), and delta PaO2 (peak PaO2 - rest PaO2, P < 0.05) in LdG versus NdG; 2) a nonsignificant decrease in peak heart rate in LdG (P < 0.13, P = 24%); and 3) significant increases in peak respiratory equivalent for oxygen (VE/VO2, P < 0.05) and delta P(A-a)O2 (peak P(A-a)O2 - resting P(A-a)O2, P < 0.05) in LdG versus NdG. No significant difference was found for PaO2 and PaCO2 at rest or at peak exercise between the groups. A strong correlation was found between pulmonary diffusion capacity (TLCO/VA) and peak VO2 (r = 0.81, P < 0.01); that is, TLCO/VA explains 66% of the variance in peak VO2. We conclude that OHT patients with decreased pulmonary diffusion capacity have a lower exercise tolerance than patients with normal pulmonary diffusion capacity. However, because of the lack of exercise-induced hypoxemia, diffusion abnormalities are not the main limiting factor for exercise tolerance in the low diffusion group.

Blood Gas Analysis↗

[Changes in blood volume in the muscles of the thigh and calf during exercise and recovery and their relationships to exercise tolerance in patients with cardiac disease].

OBJECTIVES: This study compared the blood-volume changes and recovery in the thigh and calf during leg exercise and evaluated the relationships to exercise tolerance. METHODS: The peak oxygen uptake and total hemoglobin level(blood-volume index), oxyhemoglobin level, and deoxyhemoglobin level in the thigh and calf were measured by near-infrared spectroscopy during leg ergometer exercise and recovery in 13 patients with cardiac disease(mean age: 66 +/- 6 years, left ventricular ejection fraction: 31-82%). RESULTS: There was no significant difference between the increase in blood-volume index during exercise in the thigh and that in the calf. The increase in the blood-volume index during recovery in the calf was significantly greater than that in the thigh, mainly due to the difference in deoxyhemoglobin levels. There were no positive relationships between the peak oxygen uptake and increases in blood-volume index except for the increase in blood-volume index in the thigh during exercise(r = 0.73). CONCLUSIONS: There was no significant difference between the increase in blood-volume index in the thigh and that in the calf during exercise, whereas the increase in blood-volume index during recovery in the calf was significantly greater than that in the thigh in patients with cardiac disease. Only the increase in the blood-volume index in the thigh during exercise is related to the leg-exercise tolerance in patients with cardiac disease.

Aged↗

Relationship between impaired chronotropic response, cardiac output during exercise, and exercise tolerance in patients with chronic heart failure.

The present study was undertaken to investigate the relationship between the extent of impaired chronotropic response and cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. The subjects consisted of 24 patients (mean 60.1 +/- 14.0 years) who had mild chronotropic incompetence. Cardiopulmonary exercise testing was performed in all patients, and heart rate (HR), anaerobic threshold (AT), maximum oxygen uptake (peak VO2), slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO2 slope), and exercise time were measured. Cardiac output (CO) was measured by a thoracic bioimpedance method and cardiac index (CI) was calculated. Plasma norepinephrine (NE) was measured at rest and immediately after the exercise test. The changes in HR, NE, and CI from the resting state to immediately after exercise were calculated as deltaHR, deltaNE, and deltaCI, respectively. The deltaNE was converted to a logarithmic scale and deltaHR/log deltaNE was used as a parameter of HR response to sympathetic nerve stimulation. The results were as follows: HR and NE in the resting state had no correlation with AT and with peak VO2. DeltaHR/log deltaNE correlated positively with both AT and peak VO2, and negatively with the VE/CO2 slope. DeltaHR/log deltaNE correlated positively with peak CI, %deltaCI, and deltaCI/exercise time. The data suggest that one of the mechanisms of low exercise tolerance in chronic heart failure patients was due to an inadequate increase in CO response against exercise caused by an impaired HR response to increased NE.

Adult↗

Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To determine if supervised cardiovascular training improves exercise tolerance, aerobic capacity, depression, functional capacity, and quality of life in patients with systemic lupus erythematosus (SLE). METHODS: Sixty women with SLE (ages 18-55 years) were evaluated using Short Form 36, visual analog scale for pain, scale for fatigue, Beck Depression Inventory, and Health Assessment Questionnaire (HAQ), and participated in a training protocol of incremental load on a treadmill with computed gas metabolic analysis. Maximum oxygen consumption (VO(2max)) and anaerobic threshold VO(2) were calculated with a SensorMedics Vmax29C analyzer (Sensor Medics, Yorba Linda, CA), and heart rate was measured by electrocardiogram. Patients were divided into 2 groups: a training group (41 patients) that participated in the supervised cardiovascular training program and a control group (19 patients) that did not participate in the program. All variables were analyzed at baseline and after 12 weeks for both groups. The training program occurred in the morning for 60 minutes, 3 times a week for 12 weeks. Statistical analysis included Wilcoxon's rank sum test, Mann-Whitney U test, chi-square test, and Fisher's exact test. P values <0.05 were considered to be statistically significant. RESULTS: The 2 groups were homogeneous and comparable at baseline. The training group showed a significant improvement of aerobic capacity measured by anaerobic threshold VO(2) (14.67 +/- 3.03 versus 17.08 +/- 3.35 ml/kg/minute, P < 0.001). Comparison of the training group and control group after 12 weeks showed a significant difference relating to VO(2max) (24.31 +/- 4.61 versus 21.21 +/- 3.88 ml/kg/minute, P = 0.01) and anaerobic threshold VO(2) (17.08 +/- 3.35 versus 13.66 +/- 2.82 ml/kg/minute, P < 0.0001). After cardiovascular training, we found a significant improvement of Beck inventory score (8.37 +/- 12.79 versus 2.90 +/- 3.00, P < 0.001) and HAQ score (0.14 +/- 0.21 versus 0.06 +/- 0.19, P < 0.01) in the training group. CONCLUSION: This study showed significant improvement in exercise tolerance, aerobic capacity, quality of life, and depression after a supervised cardiovascular training program in patients with SLE.

Adolescent↗

The effects on exercise tolerance of a new transdermal therapeutic system containing nitroglycerine, in patients with stable angina pectoris.

In two randomized, double blind, placebo-controlled, within patient, studies, the effects of 4 doses of a new transdermal therapeutic system containing nitroglycerin (TTS-NTG) were studied in a total of 15 patients with stable exercise-induced angina pectoris. A single 24-hour application of TTS-NTG 10 cm2, TTS-NTG 20 cm2 and TTS placebo (1st study: 6 patients) and of TTS-NTG 40 cm2, TTS-NTG 80 cm2 and TTS placebo (2nd study: 9 patients) was applied on 3 different days, and a symptom-limited cycloergometric exercise test was performed 3, 12 (only in the 2nd study) and 24 hours after the application of each treatment. In comparison with placebo, the doses tested in the 1st study induced, at the 3rd hour post-dosing, a decrease in standing systolic blood pressure and an improvement in exercise tolerance which, however, were not statistically significant while the effects at the 24th hour were similar to those of placebo. In the 2nd study, in comparison with placebo, both TTS-NTG doses induced, 3 hours post-dosing, a significant decrease in both lying and standing systolic (P less than 0.01) blood pressure at rest, and a significant (P less than 0.01) improvement in exercise tolerance throughout the 24 hours of application. It is concluded that, in patients with exercise-induced angina pectoris due to coronary artery disease, a single application of TTS-NTG 40 cm2 or 80 cm2 results in a 24-hour increase in exercise tolerance.

Administration, Cutaneous↗