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Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure. Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletal muscle energy production in male patients with congestive heart failure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercise was studied in 10 patients with chronic congestive heart failure (ejection fraction 0.22 +/- 0.05; peak oxygen consumption, VO2 15.1 +/- 4.9 ml.min-1.kg-1) and in nine healthy subjects (peak VO2 33.5 +/- 6.7 ml.min-1.kg-1). Activities of skeletal muscle enzymes were measured from the vastus lateralis muscle of 48 patients (ejection fraction 0.24 +/- 0.06, peak VO2 17.4 +/- 5.4 ml.min-1.kg-1) and 36 healthy subjects (peak VO2 38.3 +/- 8.4 ml.min-1.kg-1). RESULTS: Although blood lactate levels were lower in patients than in healthy subjects (2.2 +/- 0.3 vs 5.2 +/- 0.6 mmol.l-1; P < 0.001) at peak exercise (96 +/- 11 W for patients and 273 +/- 14 W for controls), skeletal muscle lactate was similarly elevated (25.6 +/- 3.2 vs 22.7 +/- 2.7 mmol.kg-1) and creatine phosphate was equally depressed (P < 0.02) to low levels (7.0 +/- 1.9 vs 6.7 +/- 0.9 mmol.kg-1). The muscle ATP decreased by 21% (P < 0.05) and 8% (P < 0.01) in the patients and controls, respectively. Activities of rate limiting enzymes of the citric acid cycle (alpha-ketoglutarate dehydrogenase) and oxidation of free fatty acids (carnitine palmitoyltransferase II) were 48% and 21% lower than in controls, but the mean phosphofructokinase activity was unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performance during heavy exercise is the same in congestive heart failure and healthy subjects, a high rate of skeletal muscle lactate accumulation and high-energy phosphate depletion. In congestive heart failure, the low activity of aerobic enzymes is likely to impair energy production and lead to lactate acidosis at low workloads.

Adenosine Triphosphate↗

Attenuation of hypercapnic carbon dioxide chemosensitivity after postinfarction exercise training: possible contribution to the improvement in exercise hyperventilation.

OBJECTIVE: To elucidate the responsible mechanisms of increased slope of minute ventilation relative to carbon dioxide production (VE/VCO(2)) during exercise after acute myocardial infarction without overt signs of heart failure, patients who had an acute myocardial infarction were examined after participating in a three month supervised exercise training programme. DESIGN: Exercise testing, hypercapnic CO(2) chemosensitivity measurement (rebreathing method), and pulmonary function test were repeated at entry and after three months in 50 acute myocardial infarction patients with neither symptoms nor signs of heart failure who completed the training programme. Ten patients who performed initial inhospital training served as controls. RESULTS: Age, peak oxygen uptake, left ventricular ejection fraction, CO(2) chemosensitivity, respiratory parameters (percentage of predicted normal vital capacity (%VC), forced expiratory volume in one second, and carbon monoxide transfer factor (%TLCO)) were all significantly correlated with VE/VCO(2) slope. Multivariate regression analysis showed that age (beta = 0.29, p = 0.01), %TLCO (beta = -0.27, p = 0.01), and CO(2) chemosensitivity (beta = 0.49, p < 0.001) were independent determinants of VE/VCO(2) slope. After three months, there was no significant change in these parameters in the control group. Peak oxygen uptake, %TLCO, and %VC and attenuation in CO(2) chemosensitivity increased significantly in the training group. The VE/VCO(2) slope decreased marginally (p = 0.11). The changes in VE/VCO(2) slope were correlated only with those in CO(2) chemosensitivity (r = 0.50, p < 0.001). CONCLUSION: After acute myocardial infarction, exercise hyperventilation is seen in association with aging, enhanced hypercapnic CO(2) chemosensitivity, and reduced TLCO, even in the absence of overt heart failure. The correlation of VE/VCO(2) attenuation after training with the reduction in CO(2) chemosensitivity suggests that exercise training may reduce increased VE/VCO(2) slope, at least partially by reducing CO(2) chemosensitivity.

Breath Tests↗

The effect of prolonged submaximal warm-up exercise on exercise-induced asthma.

The effect of a prolonged warm-up period of exercise on subjects with exercise-induced asthma (EIA) has been studied. Seven asthmatic subjects with known EIA were exercised according to two different protocols on two separate days, which were randomized. On Day A, subjects performed a standard 6-min treadmill run (S1A), which increased heart rate to 98% predicted maximum, followed 45 min later by an identical run (S2A). Refractoriness was demonstrated on the second exercise test, with a mean maximal fall in FEV1 of 29 +/- 3.1% and a PEFR of 32 +/- 2.8% after S2A, compared with a mean maximal fall in FEV1 of 46 +/- 2.6% and a PEFR of 51 +/- 4.0% after S1A. On Day B, subjects performed a 30-min treadmill run at a lower gradient (W1B), followed 21 min later by another standard 6-min treadmill test (S2B). W1B was followed by significantly less EIA (mean maximal fall in FEV1 of 17 +/- 5.4% and a PEFR of 21 +/- 6.3%) than followed S1A. Nevertheless, when subjects subsequently performed a standard 6-min run (S2B), significant refractoriness to bronchoconstriction, comparable to that observed after S2A, developed, with a mean maximal fall in FEV1 of 26 +/- 3.6% and a PEFR of 27 +/- 2.3% (p less than 0.05). We conclude that a warm-up period of exercise can induce refractoriness to EIA without itself inducing marked bronchoconstriction.

Adolescent↗

Exercise testing and exercise rehabilitation for patients with peripheral arterial disease: status in 1997.

Intermittent claudication is a common manifestation of peripheral arterial occlusive disease (PAOD). Patients with claudication are limited in terms of work, housework and leisure activities so that functional status is very impaired. Therefore, the goals for treatment should focus on improving the functional impairment as well as on modifying risk factors. Evaluation of the functional status is of critical importance before beginning any therapy so that any resultant changes can be assessed. A validated graded treadmill protocol and validated questionnaires are used for this purpose. Three questionnaires that are currently used include the Walking Impairment Questionnaire, the PAOD Physical Activity Recall and the Medical Outcomes Study SF-36. Exercise rehabilitation is a method that has been particularly efficacious for treating the functional impairment associated with intermittent claudication. Exercise rehabilitation has been shown to improve pain-free treadmill walking distance by 44% to 300% and absolute walking distance by 25% to 442%. In addition, improvements have also been reported (using questionnaire data) in the ability to walk distances and speeds, in amount of habitual physical activity and in physical functioning. Thus, exercise rehabilitation has caused improvements not only in exercise capacity but also in community-based functional status. Because of the benefits of this treatment, in addition to the low associated morbidity, exercise therapy is recommended as an important treatment option for people with intermittent claudication due to PAOD.

Animals↗

Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity.

STUDY OBJECTIVE: To determine the effect of an aerobic conditioning program on fitness, respiratory physiology, and resting lung function in patients with mild asthma. DESIGN: Prospective cohort study. SETTING: Outpatient rehabilitation facility. METHODS: Five patients with mild intermittent asthma and five normal control subjects completed a 10-week aerobic conditioning program. Pulmonary function studies and noninvasive cardiopulmonary exercise tests were performed before and after the conditioning program. RESULTS: After aerobic conditioning, there were significant gains in maximum oxygen consumption (VO(2)max; 22.73 mL/kg/min vs 25.29 mL/kg/min, p = 0.01, asthma; 22.94 mL/kg/min vs 27.85 mL/kg/min, p = 0.03, control) and anaerobic threshold (0.99 L/min vs 1.09 L/min, p = 0.03, asthma; 0.89 L/min vs 1.13 L/min, p = 0.01, control) in both groups. Although FEV(1) was unchanged, the maximum voluntary ventilation (MVV) improved in the asthma group (96.0 L/min vs 108.2 L/min, p = 0.08, asthma; 134.0 L/min vs 131.2 L/min, p = 0.35, control). During exercise, minute ventilation (VE) for each level of work was decreased in the asthma group after conditioning, while little change occurred in the control group (68. 48 L/min vs 51.70 L/min at initial VO(2)max, p = 0. 02, asthma; 65.82 L/min vs 63.12 L/min at initial VO(2)max, p = 0.60, control). A significant decrease in the ventilatory equivalent (VE/oxygen consumption, 40.8 vs 30.4 at VO(2)max, p = 0.02, asthma; 37.2 vs 35.8 4 at VO(2)max, p = 0.02, control) and the dyspnea index (VE/MVV) at submaximal (0.44 vs 0.38, p = 0.05, asthma; 0.32 vs 0.38, p < 0.01, control) and maximal exercise (0.72 vs 0.63, p = 0.03, asthma; 0.49 vs 0.62, p = 0.02, control) occurred in the asthma group. CONCLUSIONS: Exercise rehabilitation improves aerobic fitness in both asthmatic and nonasthmatic participants of a 10-week aerobic fitness program. Additional benefits of improved ventilatory capacity and decreased hyperpnea of exercise occurred in patients with mild asthma.

Adult↗

Therapeutic impact of exercise on psychiatric diseases: guidelines for exercise testing and prescription.

Aerobic exercise seems to be effective in improving general mood and symptoms of depression and anxiety in healthy individuals and psychiatric patients. This effect is not limited to aerobic forms of exercise. There are almost no contraindications for psychiatric patients to participate in exercise programmes, provided they are free from cardiovascular and acute infectious diseases. However, very little is known about the effects of exercise in psychiatric disease other than those in depression and anxiety disorders. A few reports indicate the need for controlled investigations in psychotic and personality disorders. Unfortunately, no general concept for a therapeutic application of physical activity has been developed so far. Reliance on submaximal measures is highly recommended for fitness assessment. Monitoring of exercise intensity during training sessions is most easily done by measuring the heart rate using portable devices (whereas controlling the exact workload may be preferable for scientific purposes). Appropriate pre- and post-training testing is emphasised to enable adequate determinations of fitness gains and to eventually allow positive feedback to be given to patients in clinical settings.

Adult↗

Exercise limitation and clinical exercise testing in chronic obstructive pulmonary disease.

Clinical exercise testing is an important tool in assessment of exercise limitation in COPD patients, in assessment of physiologic and psychological factors that contribute to exercise limitation, and in the differential diagnosis of cardiorespiratory disease. Further studies that examine the clinical utility of exercise testing are needed because there are currently insufficient data regarding the utility of many exercise variables.

Acidosis, Respiratory↗

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4&#xa0;weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45&#xa0;mL/kg/min) achieved with only ~11&#xa0;min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52&#xa0;min/session to achieve 80% of the&#xa0;maximal observed&#xa0;effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11&#xa0;min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

Journal Article↗

Effect of exercise training on the untrained limb exercise performance of men with angina pectoris.

This study examined the exercise capacity of trained and untrained limbs in men with angina pectoris before and after 8 weeks of arm ( n = 4) or leg (n = 7) physical training or a control (n = 4) period. Time to angina (mean +/- standard deviation) increased 3.6 +/- 2.7 minutes (p less than 0.01) during trained limb and 1.6 +/- 1.2 minutes (p less than 0.01) during untrained limb exercise. Myocardial oxygen demand at angina estimated by the product of heart rate and systolic blood pressure did not change with training. At a constant subanginal work load, rate-pressure product x 10(-2) was reduced by 35 +/- 22 (p less than 0.001) during trained limb and by 18 +/- 27 (p less than 0.05) during untrained limb exercise. The decrease in rate-pressure product with both trained and untrained limbs was greatest in subjects with the highest rate-pressure product at angina before training. Control subjects showed no change in any exercise measurement. Exercise training increases the exercise capacity of untrained limbs in patients with angina pectoris by a generalized training effect not dependent on adaptations in trained skeletal muscle. The improvement for both trained and untrained limbs results from a reduced rate-pressure product at subanginal work loads rather than from an increase in myocardial oxygen delivery. Subjects with the highest pretraining coronary arterial oxygen supply at the onset of angina benefit most from physical training.

Angina Pectoris↗

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↗

Exercise thallium scintigraphy versus high-dose dipyridamole echocardiography testing for detection of asymptomatic restenosis in patients with positive exercise tests after coronary angioplasty.

The usefulness of high-dose (< or = 0.84 mg/kg over 10 minutes) dipyridamole echocardiography testing was compared with that of exercise thallium-201 scintigraphy in detecting restenosis (> 70% lumen reduction) in 50 asymptomatic patients with ST-segment depression during maximal exercise testing 3 months after successful coronary angioplasty. Dipyridamole echocardiography testing and exercise thallium scintigraphy showed a similar sensitivity (75 vs 83%; p = NS) and specificity (90 vs 84%; p = NS) for the detection of restenoses, which occurred in 12 patients. It is concluded that dipyridamole echocardiography testing is as accurate as exercise thallium testing for the noninvasive detection of severe restenosis in patients with exercise-induced asymptomatic ST-segment depression after successful angioplasty. Furthermore, the site, extent and severity of the thallium perfusion defects during exercise are correlated to those of the dyssynergy during dipyridamole echocardiography.

Angioplasty, Balloon, Coronary↗

Exercise and heart disease. Epidemiology of the "exercise hypothesis".

The "exercise hypothesis" states that exercise protects against coronary heart disease. Reviewed herein is the epidemiologic evidence for and against the "exercise hypothesis." The weight of evidence supports the view that exercisers have a lower risk of coronary disease, but that vigorous exercise cannot always prevent progression of coronary atherosclerosis and does increase the risk of sudden death in persons with advanced coronary atherosclerosis. It is concluded that the "exercise hypothesis" is plausible, even likely, but still unproved.

Adult↗

Effect of endurance exercise training on plasma pancreatic polypeptide concentration during exercise.

The effect of exercise on human pancreatic polypeptide (hPP) levels was evaluated in five subjects preceding and following a conditioning program. During 90 min of exercise, the plasma concentration of hPP rose to a peak value five times higher than the resting level. After 2 mo of endurance exercise training, exercising at the same absolute work load resulted in only a twofold increase in hPP levels. Even at a higher work load, plasma hPP levels were significantly lower than the values observed prior to conditioning. These results show that plasma hPP concentrations rise during exercise and the magnitude of this response is significantly lower after 2 mo of endurance exercise training.

Adult↗

Pulmonary haemodynamics in the exercising horse and their relationship to exercise-induced pulmonary haemorrhage.

Exercise-induced pulmonary haemorrhage (EIPH) is a common occurrence in race horses. Although blood in cases of EIPH has been suspected to originate from the bronchial circulation, which receives approximately 1% of the left ventricular output, physiological evidence has recently emerged to indicate that the pulmonary circulation, which receives the entire output of the right ventricle, is a more likely source. High transmural pulmonary capillary pressures have been shown to cause breaks in the capillary endothelium, basement membrane as well as in the alveolar epithelium. Blood constituents escape into the interstitium and alveoli through such breaks in the blood-gas barrier--a phenomenon referred to as stress failure of pulmonary capillaries. Concomitant measurement of pulmonary arterial and venous pressures in strenuously exercising horses have revealed that both of these variables increased dramatically such that the intravascular pulmonary capillary pressure during exertion at 14 m/s (heart rate of 214 beats/min) approached 105 cm H2O (79 mmHg). Alveolar pressure during peak inhalation is likely to be negative; therefore, it is probable that transmural (intravascular minus perivascular) pulmonary capillary pressure of maximally exercising horses may be greater than 105 cm of water. Thus, the pulmonary blood-gas barrier, which has to be thin to provide for adequate diffusion of O2, is exposed to very high transmural forces associated with high cardiac output during exercise. Recent evidence suggests that the alveolar-capillary membrane may not be able to withstand the high transmural forces during maximal exertion, and that stress failure of pulmonary capillaries occurs, leading to EIPH. Intravenous furosemide premedication 4 h before exercise attenuates the exercise-induced rise in pulmonary arterial, capillary and venous pressures and, therefore, may be efficacious in reducing or limiting the extent of EIPH in race horses.

Animals↗

Influence of physical exercise on aging rats. III. Life-long exercise modifies the aging changes of the mechanical properties of limb muscle tendons.

We have previously shown that long-term regular physical exercise has a systemic influence on the rat by slowing the aging of its connective tissues, measured as thermal stability and biomechanical properties of tail tendons. This paper analyses whether the properties of limb muscle tendons are influenced not only by the aging process and the systemic effects of exercise but also from direct mechanical stimuli from long-term physical exercise. Male Sprague-Dawley rats were trained in a treadmill from the age of 5 to 23 months. The effects of training on muscle tendons were analyzed with respect to biomechanical properties. Also, the viscoelastic activation energies for interactions between collagen and the proteoglycan gel as well as between collagen fibrils were measured. Finally the asymptotes from the creep curves were calculated in order to estimate the magnitude of the viscoelastic creep. The effects of aging were analyzed with respect to the same parameters by comparing the group of 23-month-old sedentary rats with a 5-month-old baseline group. The biomechanical parameters did not change significantly with physical exercise. Neither did the activation energies change, but the asymptotes of the creep curves decreased, showing that there was less viscoelastic creep. Aging rendered the tendons significantly stronger and stiffer, increased the energy-absorbing capacity and decreased the strain values. The activation energies did not change with aging, but the high creep curve asymptote for the flexor tendons decreased. We conclude that aging rendered both types of tendons stiffer, and decreased their strain values at breaking point. Aging also increased the stress value, the energy absorption and the dry weight for the flexor tendon. Further, while physical exercise has a systemic delaying effect on age changes in connective tissues, in tendons subjected to substantial mechanical loads this effect as measured with biomechanical methods is counteracted by the optimization process elicited by the same physical exercise.

Aging↗