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Clofibrate effects: mitochondria vs exercise tolerance in aging hamsters.

Mitochondria in skeletal and cardiac muscle have been found to be less stable in aging hamsters, in contrast to preparations from young animals. We have found previously that clofibrate (Atromid-S) will reverse this degeneration in the older hamsters. This study examined the exercise tolerance of aged hamsters, to see if clofibrate had a parallel effect on exercise tolerance as had been shown for muscle mitochondria stability. Maximal duration of exercise for hamsters on a treadmill was measured in a control and treatment group before and after treatment with clofibrate. There was no improvement in exercise tolerance with clofibrate. We conclude that inferences of functional effects in intact animals from changes found in isolated tissue preparations should be drawn with caution.

Aging↗

[Effects of smoking tobacco on exercise tolerance in healthy subjects].

The aim of the study was to investigate the effects of smoking on exercise tolerance in middle aged smokers. Sixty two healthy subjects 55 males and 7 females with mean age 35 +/- 7 years were studied. There were 47 smokers (smoking 21.5 cigarettes per day for a mean of 16 years) and 15 non-smokers (control group). Resting pulmonary function was normal in both groups, however smokers had significantly lower VC as well as MEF 50 and MEF 75. A maximal incremental exercise on cycloergometer using ramp protocol was performed. Ventilatory parameters (breath by breath method) together with transcutaneous oxygen saturation (every minute), heart rate (continuously) and blood pressure (every minute) were recorded. Significant differences in exercise tolerance in studied groups were observed. Smokers tolerated a lower maximal workload for a shorter time and deferred significantly in both maximal oxygen consumption and oxygen consumption at anaerobic threshold. Five persons, all smokers did not reach the anaerobic threshold. In five smokers a decrease in ECG ST segment was observed. No differences were found in breathing reserve, heart reserve or maximal oxygen pulse. It seems that a decreases exercise performance is due to cardiac limitation.

Adult↗

[Exercise tolerance assessed by unilateral pulmonary artery occlusion test before and after pulmonary resection].

Pre- and post-operative exercise tests and unilateral pulmonary artery occlusion tests were performed on 15 surgical patients with pulmonary cancer. The relationship between these cardio-pulmonary parameters and exercise tolerance was studied, and pulmonary functional resectability was discussed. Pre- and post-operative anaerobic thresholds correlated with driving pressure (D.P: pulmonary artery pressure--pulmonary wedge pressure), and the pulmonary vascular-resistance index (PVRI). From the regression line and post-operative energy metabolic ratio, the standard limitation point of pulmonary resection can be estimated, (D.P = 22.6 mmHg PVRI = 621 dyne.sec.cm-5.m2). These data yielded a pulmonary pressure = 33.4 mmHg, total pulmonary vascular resistance index = 885 dyne.sec.cm-5.m2. These correlations were obtained because D.P and PVRI indicate the over all condition of the pulmonary vascular bed, gas exchange, ventilation and cardiac function. These data were in close agreement with previous results pertaining to the above indications. Unilateral pulmonary occlusion testing predicted the post-operative exercise tolerance of patients undergoing lung resection.

Aged↗

Effect of intravenous antibiotics on exercise tolerance (3-min step test)) in cystic fibrosis.

Most children with cystic fibrosis (CF) feel better and display more energy after a course of intravenous antibiotics (IVABs), but this is not always reflected by a satisfactory improvement in lung function. We assessed the change in exercise tolerance after treatment with IVABs using the 3-min step test, and compared it with changes in spirometric lung function and arterial oxygen saturation (SaO(2)). Thirty-six children (mean age, 13.8 years) were enrolled from two tertiary CF centers during an inpatient stay for IVABs. After 10-14 days of treatment, there was a significant improvement in median FEV(1) from 43% to 57% of predicted values (P < 0.0001), and median FVC from 66% to 73% of predicted values (P < 0.0001), while median SaO(2) significantly increased from 95% to 96.5% (P < 0.05). This was accompanied by a reduction in resting heart rate (median 118 bpm to 109 bpm, P < 0.005) and subjective breathlessness at rest (median visual analogue score 2.2 to 0.8, P < 0.005). All outcomes of exercise tolerance were improved after IVABs. There was a reduction in maximum heart rate (median 156 bpm to 150 bpm, P < 0.05) and an increase in minimum SaO(2) (median 93.5% to 94.5%, P = 0.08) measured during the step test. There was also a reduction in subjective breathlessness (median visual analogue score of 5.5 to 4.2, P < 0.005) and objective breathlessness (median 15-count score of 3 to 2, P < 0.0001) measured immediately after the step test. Exercise testing was a useful outcome measure for monitoring effectiveness of inpatient therapy, and complemented spirometry and SaO(2) monitoring. The simple ward-based 3-min step test was found to be a particularly suitable method for measuring changes in exercise tolerance in children with CF.

Adolescent↗

Exercise tolerance and behavior of blood pressure in children and adolescents after renal transplant.

OBJECTIVE: The purpose of the study was to evaluate the exercise tolerance and the behaviour of blood pressure during a maximal exercise testing on treadmill for a group of patients with renal transplant carried out at least 6 months earlier. EXPERIMENTAL DESIGN, SETTING AND PATIENTS: In a retrospective study, nineteen patients were examined in our laboratory: 13 boys and 6 girls, mean age 15.8 years (range 10.5-22). INTERVENTIONS: All patients were given a clinical examination, an ECG at rest, a maximal exercise testing on treadmill (Bruce protocol), a mono-2D echo, a lung function test and 24-hour Holter monitoring. The results of the exercise test were compared with those of two control groups of same age and body surface area. RESULTS: The clinical examination of their cardiovascular apparatus gave normal results. The echo revealed anatomical and heart function anomalies related to the original disease. Exercise testing on treadmill showed a reduction in exercise tolerance (p < 0.001) and the maximal heart rate showed a statistically significant difference (p < 0.001) in comparison to control groups. Maximal systolic blood pressure was higher than in patients with same body surface area (p < 0.001) and higher than in peers (p = 0.133). CONCLUSIONS: In view of this hypertensive response, strenuous physical activity should be undertaken with caution and indeed submaximal aerobic activity is more suitable for this population of patients.

Adolescent↗

Improved exercise tolerance following enhanced external counterpulsation: cardiac or peripheral effect?

The effect of treatment with enhanced external counterpulsation (EECP) on exercise hemodynamics and myocardial stress perfusion in 27 patients with chronic stable angina was studied. A majority (22/27 or 81%) of patients improved their exercise tolerance after EECP treatment, and a similar percentage (21/27 or 78%) of patients improved their radionuclide stress perfusion images. Post-EECP maximal exercise heart rate and blood pressure, while demonstrating a linear relation with exercise duration, did not increase significantly despite the increased exercise duration. This suggests that the increase in exercise duration after treatment with EECP is due to both improved myocardial perfusion and altered exercise hemodynamics. EECP therapy thus appears to exert a "training' effect, decreasing peripheral vascular resistance and the heart rate response to exercise. Coronary disease patients may improve their exercise tolerance after EECP because of both improved myocardial perfusion and a decrease in cardiac work load.

Aged↗

Echo derived variables predicting exercise tolerance in patients with dilated and poorly functioning left ventricle.

OBJECTIVE: To determine whether resting echo derived measurements predict exercise tolerance and its interrelation with heart rate response and ventilation drive in patients with systolic left ventricular disease. DESIGN: Prospective echocardiographic examination followed by cardiopulmonary exercise testing. SETTING: A tertiary referral centre for cardiac diseases. SUBJECTS: 21 patients (11 with coronary artery disease, 10 with idiopathic dilated cardiomyopathy) with end diastolic dimension > 6.4 cm, shortening fraction < 25%, and in sinus rhythm. There were 11 age matched normal controls. RESULTS: In the patients, peak oxygen consumption (mVo2) correlated with right ventricular long axis excursion (r = 0.62); 65% of the variance in mVo2 was predictable using a multivariate model with right ventricular long axis excursion and peak lengthening rate, and peak mitral atrial filling velocity as independent variables. Aetiology was not an independent predictor, although the right ventricular long axis excursion (mean (SD)) was greater in patients with idiopathic dilated cardiomyopathy than in those with coronary artery disease (2.4 (0.5) cm v 1.6 (0.5) cm, p < 0.001). Peak heart rate correlated with duration of mitral regurgitation (r = -0.52) and the slope of ventilation against CO2 production correlated with M mode isovolumic relaxation time (r = 0.61). CONCLUSIONS: In patients with systolic left ventricular dysfunction, more than half the variance in exercise tolerance can be predicted by factors measured on echocardiography at rest, particularly right ventricular long axis excursion.

Cardiomyopathy, Dilated↗

In normal postmenopausal women physiologic estrogen replacement therapy fails to improve exercise tolerance: a randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Our purpose was to test whether estrogen replacement therapy could increase exercise tolerance in postmenopausal women. STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover study in 31 healthy postmenopausal women who received 12 weeks of physiologic estrogen replacement therapy (micronized estradiol, 2 mg/day) and were evaluated with modified Balke exercise treadmill tests. RESULTS: Serum estradiol levels increased significantly during replacement therapy in this cohort of female volunteers with a mean age of 59 years, and resting heart rate was lower in women receiving estrogen replacement (p < 0.05). However, neither the heart rate nor the blood pressure responses to exercise was different, nor was the total exercise time, rate of oxygen uptake, or maximal oxygen uptake increased after estradiol treatment. Similarly, ventilatory parameters were unaffected by estradiol. The slope of the respiratory exchange ratio was slightly but significantly different (p < 0.05) while volunteers received estrogen replacement therapy. CONCLUSION: Estrogen replacement therapy, which achieves serum estradiol concentrations in the physiologic range for 12 weeks, fails to increase exercise tolerance or improve cardiovascular response to exercise in postmenopausal women.

Cross-Over Studies↗

Exercise tolerance and hyperinsulinemia in cardiac syndrome X.

The aim of the study was to evaluate the relationship between exercise tolerance, glucose and insulin levels and biochemical parameters related to endothelial function [endothelin-1 (ET-1), nitrite/nitrate (NOx)] in patients with cardiological syndrome X in comparison with healthy volunteers. The decrease of NOx level and NOx / ET-1 ratio suggests that endothelial dysfunction is present in cardiological syndrome X. Exercise tolerance correlated positively with NOx and negatively with insulin concentrations.

Adult↗

Short- and long-term effects of nisoldipine on cardiac function and exercise tolerance in patients with hypertrophic cardiomyopathy.

UNLABELLED: Nisoldipine is a second generation dihydropyridine calcium antagonist having characteristics of strong coronary artery dilating effect and less negative inotropic action. The purpose of this study was to evaluate the effect of nisoldipine on the cardiac function (systolic and diastolic) and the exercise tolerance, in patients with hypertrophic cardiomyopathy (HCM). SUBJECTS: Twenty-three patients with HCM were studied. METHODS: We measured the following indices using M-mode and pulsed wave Doppler echocardiography before and after nisoldipine therapy; left ventricular fractional shortening (LVFS), isometric relaxation time (IRT), deceleration half-time (DHT) of early diastolic mitral (E) flow, late diastolic mitral (A) flow and A/E ratio. Symptom-limited treadmill exercise test was performed. Exercise tolerance (EX) time was measured. Nisoldipine of 10 mg/day was orally administered. Same tests were repeated on day 14 and after 6 months. RESULTS: 1) Short-term effects; LVFS did not change (55.9 +/- 5.9%-->57.0 +/- 7.4%, NS) after 2 weeks. However, LV diastolic function significantly improved (IRT; 92.1 +/- 7.7 ms-->85.2 +/- 11.6 ms, p < 0.05, DHT; 70.7 +/- 16.2 ms-->63.3 +/- 3.7 ms, p < 0.05). EX time increased (8.9 +/- 2.6 min-->10.0 +/- 3.3 min, p < 0.05), 2) Long-term effects; LV diastolic function had a tendency toward improvement, but is statistically not significant (IRT; 91.1 +/- 7.6-->83.8 +/- 11.6 ms, DHT; 73.1 +/- 23.4-->61.0 +/- 11.4 ms, A/E; 1.26 +/- 0.29-->1.11 +/- 0.36) after 6 months. EX time was significantly increased (9.4 +/- 1.7--> 10.1 +/- 1.7 min, p < 0.05). CONCLUSIONS: Nisoldipine improved LV diastolic dysfunction and exercise tolerance in patients with HCM. These effects were similar to the first generation calcium antagonists. LV diastolic dysfunction may be improved due to the reduction of intracellular calcium concentration and the relief of myocardial ischemia by strong coronary artery dilating effect. However, nisoldipine did not affect the LV systolic function because of its less negative inotropic effect.

Adult↗

Influence of fluid removal rate during hemodialysis on left ventricular performance and exercise tolerance in patients with coronary artery disease.

The effect of hemodialysis (HD) on left ventricular (LV) function and exercise tolerance were measured at rest and during exercise using gated equilibrium radionuclide ventriculography in seven patients with confirmed coronary artery disease (CAD). To separate the effects of fluid removal rate on LV function in CAD, we investigated the same patients with identical overall volume loss of 4 liters during two different treatment times (4 hr and 2 hr). HD significantly increased resting LV ejection fraction (EF) from 55.7 +/- 8% to 64.7 +/- 8% (P less than 0.01) during the 4 hr HD and from 58.1 +/- 9 to 68.1 +/- 10 (P less than 0.05) during the 2 hr HD. Indicating ischemia, EF decreased at pre- and postdialysis peak exercise without differences between both treatments. HD also resulted in an improved segmental wall motion score. Exercise duration as well as S-T segment depression and angina score improved during HD, whereas heart rate, blood pressure and double product remained unchanged. We conclude that HD improves global and regional resting LV function and exercise tolerance in patients with CAD. The degree of interdialytic hydration and not the degree of fluid removal per time affects LV performance in CAD. Since LV function is the major prognostic factor in CAD, those patients require volume restriction and/or shorter interdialytic phases.

Adult↗

Tissue Doppler imaging identifies asymptomatic normotensive diabetics with diastolic dysfunction and reduced exercise tolerance.

BACKGROUND: Early recognition of heart disease in diabetics is a highly desirable goal, and diastolic dysfunction, one of its earliest manifestations, can be readily assessed by tissue Doppler imaging. We tested in normotensive diabetics without signs of coronary artery disease whether tissue Doppler imaging would improve the diagnosis of diastolic dysfunction beyond classical criteria and identify patients already presenting impaired cardiac performance. METHODS: We studied 79 patients (56 males, 55 type-2 diabetes mellitus) who underwent Doppler echocardiography, and exercise testing. Diastolic dysfunction was diagnosed either based on European Study Group on Diastolic Heart Failure guidelines or by tissue Doppler imaging provided that both of the following criteria were met: Em/Am ratio <1; and Em < 8.5 cm/sec. RESULTS: Tissue Doppler imaging identified diastolic dysfunction in 26.6% of diabetics, while classical criteria did so in 40.5% of the cases. The group identified by classical criteria did not differ significantly from patients without diastolic dysfunction, while in the group identified by Tissue Doppler imaging, significant differences were highlighted, including worse exercise tolerance and higher left ventricular mass index. Moreover, in multiple regression analysis, Em myocardial velocity and body mass index were the only variables independently related to exercise tolerance. CONCLUSION: Differently from classical criteria based on pulsed Doppler, Tissue Doppler imaging identifies a group of asymptomatic normotensive diabetics with diastolic dysfunction and reduced exercise tolerance. Confirmation of the prognostic importance of our findings could justify the use of Tissue Doppler imaging for diastolic function assessment in diabetics with otherwise healthy hearts.

Adult↗

Effect of propranolol on exercise tolerance of patients with atrial fibrillation.

Six patients with atrial fibrillation who were taking digitalis were exercised before and after 30 mg. of propranolol twice daily. Though there was a lower pulse rate at rest and on exercise in all patients, three suffered deterioration of exercise tolerance. It is concluded that propranolol does not improve the exercise tolerance of patients with atrial fibrillation whose resting ventricular rate is controlled with digitalis.

Adult↗

Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease.

Previous studies have shown that opiates increase the maximal external work performed at exhaustion in patients with chronic obstructive pulmonary disease (COPD). The mechanism responsible for this improvement in exercise tolerance is unknown. The purpose of this study was to determine the effects of an oral morphine solution (0.8 mg/kg) on the exercise tolerance, perception of dyspnea, and arterial blood gases of patients with COPD. Thirteen eucapnic patients with stable COPD (FEV1 = 0.99 +/- 0.48) underwent duplicate incremental cycle ergometer tests to exhaustion (Emax) after the ingestion of placebo and after the ingestion of morphine. After the ingestion of morphine, the maximal workload increased by 18% (p less than 0.001) and the VO2 increased by 19.3% (p less than 0.001). Ten of the 13 patients had a higher ventilation at Emax after morphine ingestion. Despite the higher ventilation at Emax after morphine, the mean Borg score was not significantly higher. At Emax after morphine ingestion, the PaO2 (65.8 +/- 11.6 mm Hg) was significantly lower and the PaCO2 (43.5 +/- 8.3 mm Hg) was significantly higher than at Emax after placebo (71.9 +/- 15.5 and 38.3 +/- 8.5, respectively). When data at the highest equivalent workload were analyzed, the ventilation and the Borg scores were significantly lower, whereas the VO2 and VCO2 were comparable. From this study, we conclude that the administration of opiates can substantially increase the exercise capacity of patients with COPD. The improved exercise tolerance appears to be related to both a higher PaCO2 resulting in lowered ventilation requirements for a given workload and also to a reduced perception of breathlessness for a given level of ventilation.

Aged↗

Exercise tolerance in patients with angina pectoris after pentaerythritol trinitrate and alprenolol studied by two different methods.

Exercise tolerance has been studied by two different methods, heart-rate-controlled exercise and stepwise increased load, in 12 patients with angina pectoris. The response to a beta-adrenergic blocking agent, alprenolol, and an alkyl nitrate derivative, pentaerythritol trinitrate (PETRIN) was studied by the two methods after double-blind administration of the drugs. Rating scales were used to quantitate the degree of dyspnoea, angina pectoris and tiredness in the legs. After PETRIN both methods showed significant increases in exercise tolerance (19 and 21 per cent). The heart-rate-controlled test showed a significant increase (33%) after alprenolol, but the change was not significant by the other method. In the patients studied, heart-rate-controlled exercise discriminated between active drug and placebo better than the stepwise increased load test, what might have been due to more optimal matching of the loads obtained in the heart-rate-controlled test. Indications are given about how to design an exercise study in patients with angina pectoris.

Aged↗

Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD.

STUDY OBJECTIVES: Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-h improvements in airflow and lung hyperinflation reduction. We hypothesized that ventilatory mechanics improvements from tiotropium would permit enhanced ability to train muscles of ambulation and therefore augment exercise tolerance benefits of PR. DESIGN: In a randomized, double-blind, placebo-controlled trial (tiotropium, n = 47; placebo, n = 44), tiotropium (18 microg qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training three times a week; >/= 30 min per session) at 17 sites. Study drug was administered 5 weeks prior to, 8 weeks during, and 12 weeks following PR. The primary end point was treadmill walking (0% incline) endurance time at 80% of maximum speed attained in an initial incremental test. The transition dyspnea index (TDI), St. George's respiratory questionnaire (SGRQ), and rescue albuterol use were secondary end points. PARTICIPANTS: Mean age of the 93 participants was 67 years, 57% were men, and mean FEV(1) was 0.88 L (34% predicted). RESULTS: Mean endurance time differences (tiotropium minus placebo) prior to PR, at the end of PR, and 12 weeks after PR were 1.65 min (p = 0.183), 5.35 min (p = 0.025), and 6.60 min (p = 0.018), respectively. Mean TDI focal scores at the end of PR were 1.75 for tiotropium and 0.91 for placebo (p > 0.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (p < 0.05). Relative to placebo, tiotropium improved SGRQ total scores by 3.86 at the end of PR and 4.44 at 12 weeks after PR (p > 0.05). Mean albuterol use declined following PR plus tiotropium, compared to PR alone (p </= 0.05 for 17 of 25 weeks). CONCLUSIONS: Tiotropium in combination with PR improved endurance of a constant work rate treadmill task and produced clinically meaningful improvements in dyspnea and health status compared to PR alone. Improvements with tiotropium were sustained for 3 months following PR completion.

Administration, Inhalation↗

Improved pulmonary function and exercise tolerance with inspiratory muscle conditioning in children with cystic fibrosis.

This study documented the effect of inspiratory muscle conditioning in children with cystic fibrosis. Subjects, ages 7 to 14 years, were divided into two groups. The experimental group (n = 10) trained at a high pressure load (> or = 29 cm H2O) and the control group (n = 10) trained at a minimal pressure load (< or = 15 cm H2O), using a threshold loading device. Subjects trained 30 min a day for 10 weeks. Pulmonary function, inspiratory muscle strength, and exercise tolerance were measured at the beginning and end of the training period. Pulmonary function was measured by body plethysmography. Inspiratory muscle strength was determined by standard measures of maximal inspiratory pressure against an occluded airway. Exercise tolerance was measured by the length of time subjects could walk on a treadmill. Findings indicated that the experimental group showed significant increases in inspiratory muscle strength, vital capacity, total lung capacity, and exercise tolerance in comparison to the control group.

Adolescent↗

Effects of enoximone on exercise tolerance in patients with mild to moderate heart failure.

To evaluate the efficacy of enoximone on exercise tolerance in patients with mild to moderate heart failure, 33 patients underwent cardiopulmonary exercise tests before and 3 hours after placebo or after receiving 25 or 100 mg of enoximone administered randomly in a double-blind manner. The electrocardiogram was monitored and blood pressure measured every minute throughout cycle ergometer exercise testing with a ramp protocol in which the work rate increased 1 W every 6 seconds after a 4-minute 20-W warm-up. Minute ventilation, oxygen uptake (VO2), and carbon dioxide output were measured every 10 seconds in order to determine anaerobic threshold (AT) and peak VO2. Five patients were excluded from evaluation before breaking the double-blind key because of insufficient data. Heart rate increased and systolic blood pressure decreased throughout the testing only in the group taking 100 mg (n = 10). Significant increases in AT (14.4 to 16.2 ml/min/kg) and peak VO2 (20.8 to 22.9 ml/min/kg) were observed in the group taking 100 mg. The increases in AT showed a dose response, namely +0.7% in the placebo (n = 9), +6.9% in the 25-mg (n = 9) and 12.5% in the 100-mg group. The work rates at the AT point increased in the 25- and 100-mg groups. These results indicate that a single oral administration of enoximone improves exercise tolerance in patients with mild to moderate heart failure.

Aged↗