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Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris.

A randomized, double-blind, placebo-controlled study in patients with clinical symptoms of stable angina pectoris and healed myocardial infarction (n = 22) has shown that oral supplementation with L-arginine (6 g/day for 3 days) increases exercise capacity (tested on a Marquette case 12 treadmill according to the modified Bruce protocol). Results suggest that the inefficient L-arginine/nitric oxide system contributes to limitation of myocardial perfusion and/or peripheral vasodilation during maximum exercise in patients with stable angina pectoris.

Adult↗

Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris.

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.

Administration, Topical↗

Effect of oral sustained-release nitroglycerin on exercise capacity in angina pectoris: dose-response relation and duration of action during double-blind crossover randomized acute therapy.

Ten men with documented coronary artery disease and stable exertional angina underwent a double-blind crossover study to examine the benefit and the duration of action on their symptom-limited exercise capacity of 2 doses (2.5 and 6.5 mg) of sustained-release nitroglycerin (SRNG). A multistage bicycle test was performed in the sitting position by steps of 30 W each 3 minutes until the onset of typical angina pectoris. It was performed 24 hours before the start of the study; 1 and 5 hours after administration of placebo, and repeated after 2.5 and 6.5 mg of SRNG administered in a double-blind crossover study according to a 4 successive days protocol. No differences appeared between administration of placebo (1 and 5 hours) and the results obtained at the first exercise test. The dose of 2.5 mg of SRNG was effective on the symptom-limited working capacity but only at 1 hour (+9%; p less than 0.01). The dose of 6.5 mg was more effective both at 1 hour (+25%; p less than 0.001) and at 5 hours (+27%; p less than 0.001). All patients had angina at a higher heart rate (+5 to 8%; p = NS [not significant] and p less than 0.01), whereas systolic blood pressure and double product tended to be slightly but insignificantly increased. S-T depression at the onset of angina was insignificantly changed with placebo, and 2.5 and 6.5 mg of SRNG. It is concluded that 6.5 mg of orally administered SRNG is effective during at least 5 hours, and that the magnitude of the benefit and its duration are dose-related.

Aged↗

[Sustained improvement in symptoms and exercise capacity up to six months after autologous transendocardial transplantation of bone marrow mononuclear cells in patients with severe ischemic heart disease].

OBJECTIVE: This study aimed at assessing the effects of autologous transendocardial transplantation of bone marrow mononuclear cells (ATTBMMC) on symptoms, exercise capacity, myocardial perfusion and contractility in patients with severe ischemic heart disease during a 6-month follow-up period. METHODS: This prospective study comprised 21 patients as follows: the first 14 patients forming the treated group, and the last 7 patients forming the control group. Initially, all patients underwent clinical and laboratory assessment, treadmill testing, echocardiography, myocardial scintigraphy, and 24-hour Holter. The bone marrow mononuclear cells (BMMC) were isolated, washed, and diluted in 0.9% saline solution for transendocardial injection in areas of viable myocardium in the treated group, (15 0.2-mL injections). All patients were reassessed in the end of 2 and 6 months of follow-up. RESULTS: The demographic data and other characteristics did not significantly differ between the groups in the initial evaluation. No major adverse events related to the ATTBMMC were observed. In the end of 6 months, a reduction in the ischemic area was observed on nuclear perfusion imaging (P=0.05), as was a significant improvement in symptoms, functional capacity, and left ventricular overall function. CONCLUSION: This study showed that transendocardial injections of BMMC are safe in human beings with ischemic heart disease associated with severe ventricular dysfunction. The effects observed in the short run were maintained up to the sixth month of follow-up.

Bone Marrow Transplantation↗

Reduced exercise capacity and stress-induced pulmonary hypertension in patients with scleroderma.

OBJECTIVES: We sought to determine the incidence of stress-induced pulmonary artery (PA) systolic hypertension in a referral population of patients with scleroderma, and to examine the relation between stress-induced pulmonary systolic hypertension and exercise capacity in this population. BACKGROUND: Early detection of patients with scleroderma at risk for pulmonary hypertension (PHTN) could lead to more timely intervention and thus reduce morbidity and improve mortality. The change in PA systolic pressure (PASP) with exercise provides a possible tool for such detection. METHODS: Sixty-five patients with scleroderma (9 men and 56 women; mean age 51 +/- 12 years [SD]), normal resting PASP, and normal resting left ventricular function underwent exercise Doppler echocardiography using a standard Bruce protocol. Tricuspid regurgitation velocity was measured before and after exercise. Exercise variables including workload achieved in metabolic equivalents (METS), total exercise time, percentage of target heart rate achieved, and PASP at rest and within 60 s after exercise were recorded. RESULTS: Thirty patients (46%) demonstrated an increase in PASP to > 35 mm Hg plus an estimated right atrial pressure of 5 mm Hg. Postexercise PASP inversely correlated to both the maximum workload achieved (r = - 0.34, p = 0.006) and exercise time (r = - 0.31, p = 0.01). In women, the correlation was more significant (r = - 0.38, p = 0.003). Patients in the lowest quartile of exercise time, with the least cardiac workload achieved, produced the highest postexercise PASP. CONCLUSION: Stress-induced PHTN is common in patients with scleroderma, even when resting PASP is normal. Stress Doppler echocardiography identifies scleroderma patients with an abnormal rise in PASP during exertion. Peak PASP is linearly related to exercise time and maximum workload achieved. Measurement of PASP during exercise may prove to be a useful tool for the identification of future resting PHTN.

Blood Pressure↗

[Prognostic factors of cardiac insufficiency: value of functional exercise capacity. Maximal oxygen consumption, anaerobic threshold].

This study concerned 43 patients with chronic cardiac failure. Twenty two patients had primary dilated cardiomyopathy and twenty one had ischaemic cardiomyopathy. Fifteen patients were in the NYHA functional Class II, 20 in Class III and 8 in Class IV. The parameters studied during a bicycle ergometric exercise stress test were the developed power (W), the duration (in seconds), the peak VO2 (in ml/kg/min), the anaerobic threshold (ml/kg/min) and pulse O2 (ml/beat). The ejection fraction and end systolic and end diastolic volumes were evaluated by M mode echocardiography. The results of the precited investigations were compared in survivors and patients who died. After 15 months, 7 patients had died and 36 survived, six of the patients who died were in NYHA Class IV. The peak VO2 was 10.1 ml/kg, the anaerobic threshold was 8.5 ml/kg and pulse 02 6.1 ml/beat in the patients who died compared to 17.6 ml/kg (p less than 0.001), 14.5 ml/kg (p less than 0.001) and 9 ml/beat (p less than 0.01) in the survivors. In addition, the ejection fraction was significantly lower in patients who died (24.7 +/- 8.3 versus 35.5 +/- 7.4%, p less than 0.001). Exercise capacity was therefore a predictive factor of mortality in cardiac failure. It is more discriminating than biological parameters such as natremia and serum adrenaline concentrations. However, these exercise stress parameters (VO2, anaerobic threshold) provide little complementary information with respect to the NYHA Classification in this study.

Adult↗

Estrogen replacement and exercise capacity in postmenopausal women: a randomized placebo-controlled study.

OBJECTIVE: We tested the hypothesis that estrogen replacement (2 mg estradiol/day, orally for 90 days) would improve cardiopulmonary and functional capacities in postmenopausal women. STUDY DESIGN: Twenty-three postmenopausal and sedentary women were divided into estrogen replacement (n = 13, 57 +/- 2 years) and placebo control (n = 10, 58 +/- 2 years) groups. They performed a cardiopulmonary exercise test before and after the intervention. RESULTS: Baseline measurements were similar between groups. Blood pressure and heart rate at rest and during exercise were unchanged by estrogen treatment, and estrogen did not alter pulmonary measurements at rest and during exercise. Oxygen consumption at anaerobic threshold, respiratory compensation point and peak exercise were lower after estrogen replacement, despite the unchanged workload and exercise time to exhaustion. In the placebo control group, no change in peak oxygen consumption, workload and time to exhaustion was found. CONCLUSIONS: Estrogen does not change cardiopulmonary responses to submaximal and maximal exercise in postmenopausal women. In addition, estrogen fails to improve exercise capacity in postmenopausal women.

Estradiol↗

Acute and chronic isosorbide dinitrate therapy in congestive heart failure: demonstration of improved exercise capacity and differing arterial and venous tolerance during chronic administration.

Thirty patients with congestive heart failure underwent a double-blind study after randomization into either isosorbide dinitrate or placebo. The initial dose (40 mg orally) of isosorbide dinitrate reduced resting and exercise pulmonary artery, pulmonary capillary wedge, and systemic blood pressure and pulmonary and systemic vascular resistance without improving exercise tolerance. Chronic dosing (40 mg orally every 6 h for 3 months) increased exercise tolerance and maintained a reduction in resting and exercise pulmonary artery and pulmonary capillary wedge pressures and pulmonary resistance, while systemic pressure and resistance returned to baseline. Chronic oral isosorbide dinitrate (40 mg every 6 h) improves exercise capacity over a 3-month period with disparate tolerance effects on systemic arterial, systemic venous, and pulmonary vasculature.

Heart Failure↗

Comparative effects of theophylline and isosorbide dinitrate on exercise capacity in stable angina pectoris, and their mechanisms of action.

While the role of nitrates in the prevention and treatment of myocardial ischemia is well established, the use of theophylline, proposed almost a century ago, is still controversial. Also controversial is its mechanism of action, initially thought to be coronary dilation. In this randomized, single-blind study, the acute effects on exercise capacity of sublingual isosorbide dinitrate (10 mg) and of intravenous theophylline ethylenediamine (7 mg/kg) were assessed in 10 patients with chronic stable angina and positive exercise test. After the administration of theophylline, the time to onset of angina, the heart rate-blood pressure product at 1-mm ST-segment depression and the exercise duration were similar to that after isosorbide dinitrate administration (9.8 +/- 2.3 vs 9.3 +/- 1.7 minutes, 207 +/- 41 vs 207 +/- 48 beats/min.mm Hg.10(-2) and 10.8 +/- 2 vs 10.4 +/- 2 minutes, respectively). Both drugs significantly (p less than 0.001) improved all these parameters compared to the baseline exercise test. The effect of the 2 drugs on the diameters of angiographically normal segments of large epicardial coronary arteries was then assessed using computerized quantitative angiography in 10 other patients with stable angina. Whereas theophylline failed to increase the coronary diameters compared to that in the baseline angiogram (2.9 +/- 0.6 vs 2.9 +/- 0.6 mm, respectively), the subsequent administration of isosorbide dinitrate resulted in an increase up to 3.2 +/- 0.7 mm (p less than 0.02). Thus, in patients with stable angina, theophylline delays the onset of angina, increases the ischemic threshold and prolongs the exercise duration to the same degree as isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effects of hydralazine on exercise capacity in pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy of pulmonary hypertension has been shown to improve hemodynamics in some patients, but the clinical benefits of this therapy have not been evaluated. We studied 14 patients who had pulmonary hypertension secondary to chronic obstructive pulmonary disease to determine the effect of hydralazine treatment on hemodynamics and maximal exercise. Baseline exercise in these subjects showed an abnormal pattern of excessive tachycardia and low stroke volumes, and the stroke volume correlated inversely with the pulmonary vascular resistance during exercise (r = -0.61, p less than 0.05). After 48 h of hydralazine there were decreases in the mean pulmonary artery pressure (43 +/- 8 to 38 +/- 8 mmHg, p less than 0.06) and pulmonary vascular resistance (3.97 +/- 0.97 to 2.88 +/- 1.28 units, p less than 0.05) measured at maximal exercise, and the maximal cardiac output was increased (8.05 +/- 2.57 to 10.13 +/- 2.79 L/min, p less than 0.05), but there was no change in symptom-limited maximal oxygen consumption (747 +/- 266 to 752 +/- 244 ml/min, p = NS). Significant increases in resting and maximal exercise values of minute ventilation and mixed venous oxygen tension were also noted with hydralazine. Repeat exercise testing after 2 to 4 months of chronic hydralazine therapy demonstrated no change in symptom-limited maximal oxygen consumption. We conclude that vasodilator therapy with hydralazine, although hemodynamically efficacious, does not increase exercise capacity in patients with severe chronic obstructive pulmonary disease and secondary pulmonary hypertension.

Exercise Test↗

[What is the exercise capacity of patients with heart infarction after surgery of heart wall aneurysms?].

29 patients with a postinfarction left ventricular aneurysm underwent an aneurysmectomy. The majority of patients exhibited a marked symptomatic improvement, a decrease in pulmonary artery pressure and an increase in cardiac index. The exercise capacity however was lower than normal in 80%. Good results were especially seen in patients with involvement of only one major coronary vessel by coronary artery disease and a good contractile function of the residual myocardium not involved by aneurysm.

Adult↗

Physiological pacing improves symptoms and increases exercise capacity in the elderly patient.

We evaluated the benefits of physiological pacing in the elderly by recruiting 13 subjects > 75 years of age, already fitted with a physiological pacing system. All had been paced for complete or Mobitz II heart block. Double blind cross over study was performed comparing exercise capacity, measuring distance walked on a 6-min walking test and time taken to climb two flights of stairs; and symptoms, evaluated by an activity of daily living questionnaire, in atrioventricular synchronous and ventricular pacing. Mean distance walked was significantly higher in atrioventricular synchronous than in ventricular pacing (360 +/- 65 m vs. 327 +/- 69 m; P < 0.01). No significant difference was found in the ability to climb stairs but there was a marked improvement in the symptomatic questionnaire score, 19 +/- 5 in physiological pacing increasing to 28 +/- 10 with ventricular. Physiological pacing in the elderly produces an increase in exercise tolerance and improves symptoms; therefore, age alone should not be a contraindication to a physiological system.

Activities of Daily Living↗

Does chronic pacing affect exercise capacity after Mustard operation for transposition of the great arteries?

Late survival after Mustard repair of transposition of the great arteries is generally good but is often characterized by progressive deterioration of ventricular function and by late postsurgical arrhythmias, thus imposing the need for permanent pacing. To evaluate how chronic pacing affects long-term exercise capacity, we compared two groups of these patients: group 1, comprising 12 patients, aged 9.0 +/- 2.6 years, without pacemaker; and group 2, comprising 18 patients, aged 9.3 +/- 2.0 years, with pacemaker. Patient evaluation included history, physical examination electrocardiograph, Holter monitoring, and echocardiography. Pacing modes were as follows: AAI (6 patients), AAIR (9 patients), VVI (2 patients), and VVIR (1 patient). At exercise test we evaluated exercise tolerance, maximum heart rate, blood pressure, oxygen consumption, and cardiac output at rest and at peak exercise. The two groups were comparable for all variables examinated. All pacemakers showed normal function. During the exercise, 11 of 12 patients in group 1 showed sinus rhythm, and in group 2, 11 patients showed sinus rhythm, 5 junctional rhythm, and 2 continuous pacing. There were no significant differences between groups. Chronically paced Mustard patients but with restoration of spontaneous rhythm during the exercise test do not show reduced exercise tolerance in comparison with nonpaced Mustard patients.

Arrhythmias, Cardiac↗

Exercise capacity in young adults with hypertension and systolic blood pressure difference between right arm and leg after repair of coarctation of the aorta.

Coarctation of the aorta represents 5-7% of congenital heart defects. Symptoms and prognosis depend on the degree of stenosis, age at surgery, surgical method and the presence of other heart defects. Postoperative complications are hypertension, restenosis and an abnormal blood pressure response during exercise. This study includes 41 patients, 15-40 years old, operated in the period 1975-1996. All were exercised on a treadmill until maximal oxygen consumption was achieved. Blood pressure was measured in the right arm and leg before and immediately after exercise, and in the right arm during exercise. Oxygen consumption was monitored and we defined an aerobic phase, an isocapnic buffering phase and a hypocapnic hyperventilation phase. The resting systolic blood pressure correlates with the resting systolic blood pressure difference between right arm and leg. A resting systolic blood pressure difference between the right arm and leg of 0.13 kPa (1 mmHg) to 2.67 kPa (20 mmHg) corresponds with a slight increase in resting systolic blood pressure. This rise in blood pressure increases the aerobic phase of the exercise test, helping the patients to achieve higher maximal oxygen consumption. A resting systolic blood pressure difference of more than 2.67 kPa (20 mmHg) corresponds with severe hypertension and causes reduction in the aerobic phase and maximal oxygen consumption. Resting systolic blood pressure and resting systolic blood pressure difference between the right arm and leg are not indicators for blood pressure response during exercise. Exercise testing is important to reveal exercise-induced hypertension and to monitor changes in transition from aerobic to anaerobic exercise and limitation to exercise capacity.

Adolescent↗

Noninvasive diagnosis of coronary artery stenosis in women with limited exercise capacity: comparison of dobutamine stress echocardiography and 99mTc sestamibi single-photon emission CT.

OBJECTIVES: To compare the accuracy of dobutamine stress echocardiography (DSE) and simultaneous 99mTc sestamibi (MIBI) single-photon emission CT (SPECT) imaging for the diagnosis of coronary artery stenosis in women. PATIENTS: Seventy women with limited exercise capacity referred for evaluation of myocardial ischemia. METHODS: DSE (up to 40 microg/kg/min) was performed in conjunction with stress MIBI SPECT. Resting MIBI images were acquired 24 h after the stress test. Ischemia was defined as new or worsened wall motion abnormalities confirmed by DSE and as reversible perfusion defects confirmed by MIBI. Significant coronary artery disease was defined as > or = 50% luminal diameter stenosis. RESULTS: DSE was positive for ischemia in 35 of 45 patients with coronary artery stenosis and in 2 of 25 patients without coronary artery stenosis (sensitivity = 78% CI, 68 to 88; specificity = 92% CI, 85 to 99; and accuracy = 83% CI, 74 to 92). A positive MIBI study for ischemia occurred in 29 patients with coronary artery stenosis and in 7 patients without coronary artery stenosis (sensitivity = 64% CI, 53 to 76; specificity = 72% CI, 61 to 83; and accuracy = 67% CI, 56 to 78 [p < 0.05 vs DSE]). In the 59 vascular regions with coronary artery stenosis, the regional sensitivity of DSE was higher than MIBI (69% CI, 62 to 77 vs 51% CI, 42 to 59, p < 0.05), whereas specificity in the 81 vascular regions without significant stenosis was similar (89% CI, 84 to 94 vs 88% CI, 82 to 93, respectively). CONCLUSION: DSE is a useful noninvasive method for the diagnosis of coronary artery stenosis in women and provides a higher overall and regional diagnostic accuracy than dobutamine MIBI SPECT in this particular population.

Coronary Angiography↗

Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes.

CONTEXT: Despite the fact that the use of GH as a doping agent in sports is widespread, little is known about its short-term effects. OBJECTIVE: The objective was to study the effects of GH on exercise capacity. DESIGN: A double-blind, placebo-controlled study was used, with a treatment period of 28 d. SETTING: Subjects from general community studied ambulatory at a university hospital. PARTICIPANTS: Thirty healthy active young normal volunteers (15 women and 15 men) were recruited by local announcement, and all completed the study. INTERVENTION: All subjects were randomized to receive a low GH dose (0.033 mg/kg.d or 0.1 IU/kg.d), a high GH dose (0.067 mg/kg.d or 0.2 IU/kg.d), or placebo. MAIN OUTCOME MEASURES: Power output and oxygen uptake on bicycle exercise were the main outcome measures. RESULTS: We found no effect of the low or high dosages of GH on maximum oxygen uptake during exercise (mean +/- se for placebo, 45.2 +/- 1.6 to 45.2 +/- 2.1 ml/kg.min; GH low dose, 42.8 +/- 1.6 to 42.8 +/- 1.6 ml/kg.min; GH high dose, 44.8 +/- 3.4 to 44.8 +/- 2.2 ml/kg.min; not significant by two-way ANOVA). Neither was there any effect on maximum achieved power output during exercise or on blood pressure, heart rate, or the electrocardiographic ST level at rest or during exercise. GH significantly increased total body weight (P = 0.028), an effect predominantly ascribed to fluid retention (increased extracellular water volume), whereas muscle mass (as indicated by intracellular water volume) did not change. However, changes in the latter correlated to changes in physical performance, possibly due to different training efforts. CONCLUSION: Administration of supraphysiological recombinant human GH during a period of 4 wk does not improve power output or oxygen uptake.

Blood Pressure↗

Diltiazem versus propranolol in essential hypertension: responses of rest and exercise blood pressure and effects on exercise capacity.

Both beta-blocking and calcium channel-blocking drugs are being used with increasing frequency as initial therapy for essential hypertension. The present study was designed to compare the antihypertensive effects of a beta-blocking drug, propranolol, with a calcium channel-blocking drug, diltiazem, at rest and during upright bicycle exercise and to determine whether exercise capacity is altered by these therapies. Twenty-one patients with uncomplicated systemic hypertension and a diastolic blood pressure (BP) of 95 to 110 mm Hg without medication were randomly assigned to propranolol or diltiazem therapy in a double-blind manner. The total daily dosages were titrated as needed, from 160 to 480 mg of propranolol (mean 371 mg) and 120 to 360 mg of diltiazem (mean 307 mg) over 12 weeks, and the titrated dose was maintained for 4 additional weeks. Both drugs significantly reduced supine BP (from 149 +/- 14/101 +/- 4 to 136 +/- 17/89 +/- 10 mm Hg with propranolol and from 157 +/- 14/103 +/- 4 to 144 +/- 13/93 +/- 8 with diltiazem. Only diltiazem reduced BP during submaximal exercise, but both agents produced significant responses during maximal exercise. Diltiazem had no effect on maximal heart rate, exercise duration or O2 uptake, whereas propranolol reduced maximal VO2 from 27 +/- 6 to 22 +/- 6 ml/min/kg (p less than 0.01) and also shortened duration of exercise. Propranolol, despite its effects on heart rate, maintained the workload VO2 relation at submaximal loads, suggesting an increased oxygen delivery. However, these adaptive mechanisms appear to be insufficient during maximal effort.

Blood Pressure↗