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Acebultolol: basis for the prediction of effect on exercise tolerance.

Twelve unselected males suffering from documented coronary insufficiency and moderately severe angina submitted to graded multistage treadmill exercise testing on 3 separate days, 3.5 hr after a single dose of 0,200, or 400 mg of acebulolol, a cardioselective beta blocker. Control measures included random allocation of 2 patients to each of 6 balanced sequences of administration, standardized double-blind conditions, and variance analysis for Latin-square design with repeated measures on each subject. Performance was evaluated by measuring time elapsed until anginal pain, peak heart rate, peak product of heart rate and blood pressure, and peak oxygen consumption. Mean values for all criteria were significantly atered by 400 mg of acebutolol. Seven out of twelve patients were classified as responders (i.e., exercise duration increased 100% or more). The response after acebutolol was correlated with the performance on placebo in the base of exercise duration, peak heart rate, and peak product of heart rate and blood pressure. It is concluded that: (1) performance criteria are useful predictors of response to beta blockade and (2) acebutolol is a potent antianginal agent when judged by an objective treadmill exercise test.

Acebutolol↗

Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction.

Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine.

BACKGROUND: Neuromuscular symptoms and impaired muscle energy metabolism have been described in subclinical hypothyroidism (sHT). AIM: The aim of the study was to evaluate the energy and substrate response to exercise in sHT patients using a standardized protocol and to test the effect of L-T(4) replacement in a double-blind, randomized, placebo-controlled fashion. PATIENTS AND METHODS: We studied 23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO(2)), carbon dioxide output, and heart rate were measured during incremental step-up exercise. Blood glucose, lactate, pyruvate, free fatty acid, glycerol, and beta-hydroxybutyrate concentrations were measured at rest, every 2 min during exercise, and during 20 min of recovery. The exercise protocol was repeated after 6 months of placebo or L-T(4)-restored euthyroidism. RESULTS: Maximal power output (P = 0.02) and VO(2) max (P = 0.04) were reduced in sHT, and, with increasing workload, patients achieved higher heart rates (P < 0.03) at VO(2) values equivalent to those of controls. The respiratory quotient increments were significantly higher in patients than controls (P < 0.04). Blood lactate and pyruvate and their ratio rose with a steeper slope (P < 0.0001, P < 0.001, and P < 0.01, respectively) in patients than controls. Resting plasma free fatty acid and blood glycerol levels were significantly higher in patients than controls (P < 0.0003 and P < 0.003, respectively) throughout baseline, exercise, and recovery. L-T(4) replacement, while improving neuromuscular symptoms, did not produce significant changes in the energy or substrate response to exercise. CONCLUSIONS: The response to exercise is altered both in terms of tolerance and pattern of substrate utilization in sHT patients. Restoring stable euthyroidism does not correct this defect over a 1-yr period.

Adult↗

Increased exercise tolerance after oral diltiazem, a calcium antagonist, in angina pectoris.

Effects of diltiazem, a recently introduced calcium antagonist, on exercise performance were studied in nine coronary disease patients with effort angina. The duration of exercise before the onset of angina and the time to the onset of ischemic ST depression 2 hours after 90 mg of oral diltiazem were compared with those 2 hours after oral placebo and a few minutes after 0.3 mg of sublingual nitroglycerin. Diltiazem prolonged the duration of exercise in all nine patients (average 2.5 minutes, p less than 0.001) and delayed the onset of ischemic ST depression (average 2.4 minutes, p less than 0.001). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 90 mg of oral diltiazem were almost equivalent to that following sublingual nitroglycerin. These results in fixed coronary atherosclerosis indicate the clinical antianginal efficacy of diltiazem which persists for at least 2 hours after oral administration.

Adult↗

Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.

BACKGROUND: We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. METHODS: We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. FINDINGS: Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. INTERPRETATION: Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.

Angiotensin II↗

[Exercise tolerance after correction of tetralogy of Fallot].

Twenty-six postoperative patients with tetralogy of Fallot (TF) were evaluated by exercise stress test with an upright cycle ergometer. Oxygen uptake was assessed at the anaerobic threshold and the peak achieved work load. Oxygen uptake at the anaerobic threshold (VO2AT) was in the normal range regardless of the existence of residual stenosis (PS) or pulmonary regurgitation (PR). However, oxygen uptake at the peak achieved workload (VO2max) was subnormal in patients with PS or PR. Maximal heart rate in TF patients was lower than normal. Patients with PR showed significantly reduced VO2max as compared with those without PR (p less than 0.05). This is found to be resulted from limitation of the oxygen pulses increase.

Adolescent↗

Normoxic and acute hypoxic exercise tolerance in man following acetazolamide.

The influence of acetazolamide (ACZ) upon the ability to perform and sustain maximal and submaximal exercise bouts under normoxic and hypoxic conditions was examined in four groups of healthy male subjects (N = 27). ACZ (500 mg) or inert placebo (Pla) was administered prior to exercise in a quasi-randomized, double-blind, crossover fashion. ACZ was shown to lower venous pH (ACZ, 7.31 +/- 0.01, vs Pla, 7.35 +/- 0.08) and bicarbonate (ACZ, 22.4 +/- 0.27 mM, vs Pla, 25.4 +/- 0.6 mM) and to elevate urine pH (ACZ, 7.36 +/- 0.06, vs Pla, 5.84 +/- 0.19) and tended to elevate VE (P = 0.07) at rest. Peak VO2 measured using a continuous incremental protocol was unaltered in normoxia, while peak VCO2 and RER were lowered by ACZ. No significant effect of ACZ upon VO2, VCO2, RER, or heart rate (HR) was observed during submaximal exercise (75% of peak VO2) although VE was increased by 14% and time to exhaustion (EXHt) was reduced by 29%. During acute hypoxia at a simulated altitude of 4,270 m (Pbar = 446 mm Hg), no significant differences were noted in VE, VO2, VCO2, RER, HR, or arterial saturation (SaO2) at rest. Prior to exercise, venous pH (ACZ, 7.39 +/- 0.04, vs Pla, 7.44 +/- 0.007) and bicarbonate were lower with ACZ (ACZ, 21.6 +/- 0.46 mM, vs Pla, 24.2 +/- 0.25 mM), while urine pH was higher (ACZ, 7.6 +/- 0.07, vs Pla, 5.9 +/- 0.25). Other than a higher PCO2 and lower venous lactate with ACZ, no significant differences were identified at peak VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

Does an aortopulmonary shunt before repair of tetralogy of Fallot limit exercise tolerance in long-term survivors?

The purpose of this study was to evaluate the impact of an aortopulmonary shunt on exercise capacity in long-term survivors after total repair of tetralogy of Fallot (17.6(2.0) years' follow-up). Submaximal exercise tests, pulmonary function tests, lund diffusion tests for carbon monoxide, two-dimensional and Doppler echocardiography were performed in 12 patients with an aortopulmonary shunt (group A) and in 21 patients (group B) without a shunt before repair. There were no significant differences in two-dimensional and Doppler echocardiographic findings nor in pulmonary function. Group A showed a significantly lower diffusion capacity of the lung for carbon monoxide at rest (66.2(13.0)% versus 84.1(9.5)%; P < 0.01) and at the anaerobic threshold (71.8(11.0)% versus 87.2(9.8)%; P < 0.01) as well as a significantly reduced physical working capacity at ventilatory anaerobic threshold (1.6)(0.32) W/kg versus 2.41(0.43) W/kg; P < 0.01). A negative correlation was observed between the duration of palliative shunts and diffusion capacity of the lung for carbon monoxide at rest at ventilatory anaerobic threshold (r = -0.8635 and -0.9108 respectively). A shunt placed before definitive repair impairs the long-term working capacity, probably by diminishing the diffusion capacity of the lung for carbon monoxide, especially if the shunt is in place for more than 20 months.

Adolescent↗

[Exercise induced hypoxemia and exercise tolerance in patients with COPD and the benefits of oxygen supplementation].

In order to evaluate the benefits of O2 supplementation during exercise, slowly incremental treadmill exercise tests were performed twice with 30 minutes interval rest in fourteen patients with severe COPD. The patients breathed room air. 31/min of compressed air by nasal prongs, and 31/min of supplemental oxygen in single blind fashion at random. The patients who developed arterial desaturation below 88% on exercise, group D, showed slight but significant increase in walked distance (397 m vs 424 m) and significant decrease in breathlessness (22.9 vs 16.9) on oxygen as compared to on air. On the other hand in patients without significant arterial desaturation, group S, there was no improvement in those parameters. The increase in walked distance on oxygen was closely related with the decrease in mean inspiratory flow (VT/Ti), blood lactate level, and CO2 production at identical work load. Plasma human atrial natriuretic peptide (h-ANP) levels in group D increased with exercise from a resting value of 27.6 +/- 6.9 to 44.0 +/- 9.0 on compressed air whereas the increase was significantly suppressed to 35.4 +/- 9.0 on oxygen. In group S there was no difference in the increase of plasma h-ANP levels between air and oxygen breathing during exercise (33.1 +/- 5.1 vs 31.9 +/- 9.6). A close correlation (r = 0.908) was found between mean pulmonary artery pressures and plasma h-ANP levels at rest and during exercise performed in four patients breathing air and oxygen. Those findings suggested that arterial plasma h-ANP levels reflected the right ventricular afterload and that they could be used to evaluate the effectiveness of O2-supplementation during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of nicorandil on exercise tolerance in patients with stable effort angina: a double-blind study.

Effects of nicorandil, a recently introduced 2-nicotinamidethyl nitrate, on exercise performance were studied in 11 patients with stable effort angina. The duration of exercise before the onset of angina and time to the onset of ischemic ST depression 30 minutes after 20 mg of oral nicorandil were compared with events 30 minutes after oral placebo and 5 minutes after 0.3 mg of sublingual nitroglycerin. Nicorandil and placebo were given according to the randomized double-blind method. Nicorandil prolonged the duration of exercise in all 11 patients by 2.3 +/- 2.2 minutes (mean +/- SD, p less than 0.01) and delayed the onset of ischemic ST depression by 2.3 +/- 1.7 minutes compared to placebo (p less than 0.01). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 20 mg of oral nicorandil were almost equivalent to findings after sublingual nitroglycerin (by 2.0 +/- 1.8 and 2.5 +/- 1.7 minutes, respectively). Nicorandil also increased the pressure-rate product at the time of angina compared with placebo (20,420 +/- 480 vs 17,480 +/- 370, p less than 0.05). These results indicate that oral administration of nicorandil should be considered for the clinical treatment of effort angina.

Aged↗

Diastolic mechanisms of impaired exercise tolerance in aortic valve disease.

In order to determine the significance of abnormalities of diastolic function in patients with left ventricular hypertrophy, exercise echocardiography to heart rates of 140 to 150 beats/min was performed in 18 normal subjects and 14 patients after aortic valve replacement. Simultaneous echo-, phono-, and electrocardiograms were recorded. Left ventricular cavity size was determined at end-diastole and end-systole. The timing of mitral valve opening and closure was measured, and hence left ventricular filling time derived, expressed either as ms/beat, or s/min when multiplied by heart rate. Isovolumic relaxation was taken as the interval between A2 and mitral valve opening. Systolic function, assessed from cavity dimensions, peak VCF, and QA2 interval was normal in all but two patients at rest and on exercise. Isovolumic relaxation was prolonged at rest in the patients to 85 +/- 8 ms (normal 69 +/- 9 ms), but left ventricular filling times were normal. With exercise, in normal subjects, isovolumic relaxation remained constant, but filling times dropped strikingly from 380 +/- 66 ms/beat, or 27 +/- 2 s/min at rest to 115 +/- 10 ms/beat or 16 +/- 2 s/min. In patients with left ventricular hypertrophy, isovolumic relaxation dropped on exercise to 41 +/- 15 ms. Filling periods were normal at rest, 367 +/- 67 ms/beat or 27 +/- 3 s/min, but failed to show the normal drop with exercise, being 240 +/- 44 ms/beat or 28 +/- 4 s/min. At heart rates above 120/min, separation between the two groups was complete. Thus, striking abnormalities of left ventricular filling can be demonstrated on exercise in patients with left ventricular hypertrophy. They appear to represent loss of mechanisms whereby rapid diastolic filling is achieved in the normal subject.

Aged↗

Nitroglycerin-induced improvement in exercise tolerance and hemodynamics in patients with chronic rheumatic heart valve disease.

Nitroglycerin reduces elevated left ventricular filling and pulmonary arterial pressures in resting patients with rheumatic valve disease and reduces symptoms when given over long periods to patients with primary myocardial disease. To determine whether nitroglycerin may prove effective therapeutically in ambulatory patients with heart valve disease, its effects on hemodynamics and exercise capacity were studied in 11 severely symptomatic adults who were already receiving optimal treatment with digitalis and diuretic agents. Seven had predominant mitral valve disease, one had predominant aortic insufficiency and three had equally severe mitral and aortic valve disease. Maximal exercise capacity was assessed with graded treadmill exercise after placebo and after nitroglycerin (0.5 mg sublingually) administered in random sequence to each patient. Exercise capacity (exercise time to limiting fatigue or dyspnea) increased from a mean of 8.3 minutes after placebo to 9.8 minutes after nitroglycerin (P less than 0.005). Eight patients were studied hemodynamically during further intense treadmill exercise. Pulmonary arterial pressure was significantly lower (P less than 0.05) after nitroglycerin than after placebo (mean 44 versus 56 mm Hg), but cardiac output was greater after nitroglycerin (5.0 versus 4.6 liters/min, P less than 0.005). Thus, nitroglycerin appears to increase exericse tolerance and improve the hemodynamic response to exercise in patients with heart valve disease and may be valuable in the long-term pharmacologic therapy of such patients.

Administration, Oral↗

Cardiorespiratory responses during cycle ergometer exercise with different ramp slope increments in patients with chronic obstructive pulmonary disease.

OBJECTIVE: The ramp exercise test has been widely used to evaluate cardiopulmonary responses to an incremental exercise load. This study was performed to clarify whether different slopes of the ramp exercise test influence exercise tolerance, exercise limiting factors, and respiratory pattern in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: We applied three different slopes (5 W/min, 10 W/min and 20 W/min) of the ramp exercise test in 9 patients with COPD and evaluated cardiopulmonary responses. RESULTS: There were no significant differences in peak oxygen uptake, anaerobic threshold (AT), minute ventilation, heart rate, arterial oxygen saturation, expired tidal volume, or respiratory rate at the maximal load among the three different ramp exercises tested. AT could be determined in six of nine patients (67%) at the slope of 5 W/min, in 8/9 (89%) at the slope of 10 W/min, and in 9/9 (100%) at the slope of 20 W/min. CONCLUSION: The findings suggest that the ramp slope does not affect exercise tolerance, exercise limiting factors, or respiratory patterns and each of these ramp slopes is useful for the evaluation of COPD. Ramp slopes of 10 W/ min or 20 W/min should be appropriate for the determination of AT.

Aged↗