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Objective: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. Design: Single centre double-blind randomized placebo controlled trial. Setting: Cardiac rehabilitation centre. Subjects and intervention: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. Main Measures: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. Results: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. Conclusion: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. beta1-tubulin is the major isoform within platelet and megakaryocyte microtubules. In 24.2% of 33 unrelated inherited macrothrombocytopenia patients and in 10.6% of 272 subjects of a healthy population a P for Q substitution in beta1-tubulin was found in the highly conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced platelet protein beta1-tubulin expression. Transfection of green fluorescent protein (GFP)-tagged Q43P beta1-tubulin in megakaryocytic MEG01 cells resulted in a disturbed tubulin organization. Electron microscopy revealed enlarged spherocytic platelets with a disturbed marginal band and organelle-free zones. In addition, platelets with the Q43P beta1-tubulin variant had reduced adenosine triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced aggregation and collagen adhesion. The prevalence of the Q43P beta1-tubulin variant was also 2 times higher (odds ratio, [OR] = 2.1;95% confidence interval [CI], 1.22-3.59) among control subjects than among patients with cardiovascular disease (10.4% versus 5.2%, P < .001). By analyzing this protective factor in men and women separately, this association was only found in men. This study thus presents the functional consequences of the platelet Q43P beta1-tubulin substitution that is frequent in the healthy population and may protect men against arterial thrombosis. ispartof: Blood vol:106 issue:7 pages:2356-2362 ispartof: location:United States status: published

Summary Objective: The effect of increasing work rate was studied on the determinants of the oxygen deficit. Methods: Exercise testing was performed on a treadmill and gas exchange was measured on a breath-by-breath basis. Eleven healthy subjects, aged 18–25 years, performed three square wave exercise tests of different intensity. Before exercise, gas exchange was measured at rest in the standing position for 3 min, followed by a 6-min square wave exercise test, randomly assigned at 4, 8 or 12% inclination. Immediately after exercise the recovery gas exchange was determined for 3 min. To calculate oxygen deficit, the oxygen uptake (O2) values at onset of exercise were subtracted from the steady-state value, the differences were cumulated and expressed as a percentage of the total oxygen cost for the 6-min exercise. Results: The oxygen deficit increased significantly (P

Aims This study compares the functional outcome and cardiorespiratory response to exercise, in patients who have undergone arterial switch for transposition of the great arteries, with normal controls and patients who have undergone atrial switch operation. Methods and Results Fifteen patients who had undergone arterial switch (mean age 8·5±2·9 years) were compared to 32 patients who had undergone atrial switch (9·2±1·8 years) and 27 normal controls (8·5±2·1 years). Exercise testing was performed on a treadmill and gas exchange measured breath-by-breath. Aerobic capacity, assessed by determination of the ventilatory anaerobic threshold, averaged 91±7·8% of normal (95% confidence limits: 92–108%) for arterial switch and 75·1±13·1% for atrial switch ( P

The aim of this preliminary study was to compare exercise performance and the effect of exercise training in cardiac patients with and without an implantable cardioverter-defibrillator (ICD). There are few data on exercise performance and on the effect of exercise training in patients with an ICD. Data in patients with an ICD (n = 8) were compared with those from a matched control group (n = 16). Patients performed maximal cycle-ergometer testing before and after 3 months of exercise training. All patients had to stop the exercise test for reasons of exhaustion. The predetermined heart rate threshold in ICD patients, set at the detection rate of the ICD minus 30 beats/min, was not reached. Before training, peak oxygen uptake was not different in the ICD patients compared with the control group (21.0 +/- 6.9 vs 21.9 +/- 5.0 ml oxygen standard temperature pressure dry/min/kg). Exercise training increased peak oxygen uptake to a similar extent in both groups, 20% and 24%, respectively. One ICD patient developed uneventful ventricular tachycardia at the end of the post-training exercise test, and another during training. Thus, exercise performance and the favorable response to a 3-month exercise training program are comparable in patients with ICD and matched control patients. However, tachyarrhythmias may occur during exercise testing or training and require special attention. Selected patients with ICD can be encouraged to participate in medically supervised exercise training programs. The results of this study should be confirmed with additional studies on larger numbers of subjects.

The aim of the present study was to investigate the reproducibility of the exponential method of CO2 rebreathing with the use of automated curve fitting and to determine whether this method is superior to the equilibrium method in terms of reproducibility and clinical practicability.Repeated measurements of cardiac output were performed using the automated equilibrium and exponential methods. These measurements were compared in 12 healthy male subjects at rest and during incremental exercise tests.Estimated cardiac output was not significantly different between duplicate measurements at rest nor at any level of exercise with either method. At rest the exponential method showed a tendency toward larger variability than the equilibrium method. The exponential method produced significantly higher (Por = 0.001) estimates at rest (averaging up to 9.8 L x min(-1)) compared with the equilibrium method (averaging up to 6.5 L x min(-1)). Reproducibility improved for both methods with increasing workloads, and a second measurement at rest also seemed more reproducible and valid than the first. During exercise, both methods produced comparable values for cardiac output, and highly significant relations between cardiac output and oxygen uptake were observed for both methods (ranging from r2 = 0.79 to r2 = 0.88, Por = 0.001). The equilibrium method produced unpleasant side effects more frequently (75% vs 21%, Por = 0.001) compared with the exponential method and lead more subjects to premature interruption of the exercise test because of the rebreathing maneuver (42% vs 17%, P = 0.058).Automated curve fitting for the exponential method gave reproducible and valid results during submaximal and maximal exercise but not at rest. The equilibrium method on the other hand interfered with exercise. Therefore, the equilibrium method is recommended at rest and at lower levels of exercise and the exponential method at higher intensities.

Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD).935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene.Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P0.001). Associations of P0.05 were found between aerobic power and the eNOS 273CT variant and the catalase -262CT variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P0.05). After Bonferroni correction of multiple testing no significant differences remained.We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.

AIMS The heritability of aerobic power and of the response to physical training has been shown in healthy subjects. beta(1)-Adrenergic receptor (beta(1)AR) function affects exercise performance. This study aims to investigate whether the Ser49Gly and Gly389Arg polymorphisms of the beta(1)AR gene or their haplotypes are associated with aerobic power or its response to physical training in coronary artery disease (CAD). METHODS AND RESULTS Nine hundred and thirty-five biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of exercise training from 1990 to 2001 (n = 1095) were eligible for inclusion in the CAREGENE (CArdiac REhabilitation and GENetics of Exercise performance) study. Polymorphisms were detected using the invader assay (Third Wave Technologiestrade mark, Madison, Wisconsin, USA). Patients with the Gly49Gly genotype had significantly higher covariate-adjusted aerobic power at baseline than those with Ser49Ser and Ser49Gly (P < 0.05). Adjusted aerobic power at baseline was highest in the Ser49-Gly389/Gly49-Gly389 and Gly49-Arg389/Gly49-Arg389 haplotype combinations. Aerobic power increased significantly (P < 0.001) with physical training. There was no association with the effect of physical training. CONCLUSION Ser49Gly and haplotype combinations of Ser49Gly and Gly389Arg of the beta(1)AR gene are associated with aerobic power, but not with the response to physical training in patients with CAD included in the CAREGENE study.

The Oxygen Uptake Efficiency Slope (OUES), a new parameter derived from respiratory gas analysis, has been suggested as a submaximal index of cardiopulmonary functional reserve. We evaluated the clinical application and the effect of physical training on the OUES in patients with coronary artery disease (CAD). Maximal cycle-ergometer testing with respiratory gas analysis (breath-by-breath) was performed in 590 patients with CAD and again after three months of physical training in 425 patients. OUES was determined from the linear relation of oxygen uptake (V.O (2)) vs. the logarithm of pulmonary ventilation (V (E)) during exercise, i.e. V.O (2) = a log (10) V (E) + b, where a is the OUES. The ventilatory anaerobic threshold (VAT) and the slope of the relation of V (E) nu carbon dioxide production (V.CO (2)) (V (E)-V.CO (2) slope) were also determined. Correlation coefficients of the relation from which OUES was derived in individuals averaged 0.975 +/- 0.024 (mean +/- SD) when calculated from data up to a respiratory gas exchange ratio of 1.0. Submaximal OUES was marginally lower (5.4 +/- 7.9 %, p < 0.05) than the OUES calculated from 100 % of respiratory exercise data. Of all submaximal parameters, submaximal OUES (r = 0.837, p < 0.001) and VAT (r = 0.860, p < 0.001) correlated best with peak V.O (2), followed by V (E)-V.CO (2) slope (r = - 0.469, p < 0.001). OUES was lower in patients who underwent coronary artery bypass grafting as compared with patients after coronary angioplasty (p < 0.05). Peak V.O (2) and OUES increased significantly (p < 0.001) after training with 24 +/- 19.2 % and 20.9 +/- 19.3 %, respectively. Changes in peak V.O (2) correlated better with changes in OUES and in VAT (r = 0.61 and r = 0.55, p < 0.001, respectively) than with changes in V (E)-V.CO (2) slope (r = - 0.171, p < 0.001). The submaximal OUES is clinically useful for the quantification of exercise performance and is sensitive to physical training in patients with CAD.

Patients with congenital heart disease can usually perform low intensity exercise as well as healthy peers, but often have difficulty in reaching maximal exercise intensity. However, formal exercise testing has repeatedly shown impaired values for cardiorespiratory exercise performance.1 A considerable number of patients may complain of exercise intolerance and dyspnoea at heavy intensities of exercise. The aim of this study was to assess the efficiency of the ventilatory response to exercise by means of breath by breath analysis of gas exchange. Special attention was paid to total ventilation and alveolar ventilation as the difference between these values reflects the physiological dead space ventilation (VD), and is used as an index of ventilatory efficiency during exercise. More specifically, we assessed how the ventilatory response during exercise was affected by the clinical result of surgery and whether this correlated with the functional status after surgery for congenital heart disease. To study whether an inefficient ventilatory response to exercise could be related to the effect of a sternotomy, the ventilatory response to exercise in the present group of patients was compared with a group of age matched patients who had also undergone sternotomy for surgical closure of a ventricular septal defect (VSD). One hundred and six patients were used for this analysis. At a routine outpatient visit, the patients were clinically assessed, and also underwent echocardiographic, electrocardiographic, and radiological examinations. Three patient …

Aims Little research exists on exercise performance and training in patients with an implemented cardioverter defibrillator (ICD) and only in a limited number of patients. This study aims to investigate the effect of exercise training in ICD patients in comparison to the effects in other cardiac patients without an ICD. Methods and results 92 ICD patients were compared with a control group of 473 patients. A maximal cycle-spiroergometric test was performed until exhaustion before and after an ambulatory exercise training programme. Exercise training was offered 3 times a week for 3 months. The cut-off heart rate was set at (ICD detection rate −20 beats/min). At baseline, the ICD patients had a lower peak oxygen uptake (VO2) compared to the control group. Training effects were smaller for peak VO2 (mL/min/kg) and oxygen pulse in the ICD group (18 vs. 27%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.006\) \end{document} and 11 vs. 17%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.016\) \end{document}, respectively). Several appropriate shocks were delivered during (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=5\) \end{document}), and in between (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=7\) \end{document}), testing or training and one inappropriate shock during training. Conclusions ICD patients can safely participate in an exercise training programme with favorable results. A randomised control study with evaluation of the physical and the psychosocial effects is warranted.

The effect of increasing work rate was studied on the determinants of the oxygen deficit.Exercise testing was performed on a treadmill and gas exchange was measured on a breath-by-breath basis. Eleven healthy subjects, aged 18-25 years, performed three square wave exercise tests of different intensity. Before exercise, gas exchange was measured at rest in the standing position for 3 min, followed by a 6-min square wave exercise test, randomly assigned at 4, 8 or 12% inclination. Immediately after exercise the recovery gas exchange was determined for 3 min. To calculate oxygen deficit, the oxygen uptake (O2) values at onset of exercise were subtracted from the steady-state value, the differences were cumulated and expressed as a percentage of the total oxygen cost for the 6-min exercise.The oxygen deficit increased significantly (P0.001) with increasing work rate (6.1 +/- 1.4% for 4%, 8.4 +/- 2.1% for 8% and 9.4 +/- 1.7% at 12% inclination). This resulted from a somewhat slower increase of O2 at the onset of exercise at the highest work rate, reflected by a significantly higher time constant for O2 at 8 and 12% (24.6 +/- 7.3 s at 8% and 24.1 +/- 6.3 s at 12% versus 20.2 +/- 8.1 s at 4%). More importantly a significantly higher steady-state value for O2 was found at the highest exercise level, compared with the other exercise intensities.The higher oxygen deficit at the highest level of exercise is determined by a slower time constant and a higher asymptote value for O2.

PURPOSE Exercise training in cardiac patients with chronic atrial fibrillation (AF) has received little attention in the literature. Therefore, this study compared exercise performance and the effect of an exercise training program over a period of 3 months in patients with and without AF. METHODS Data in patients with AF (n = 19) were compared with a control group of patients in sinus rhythm (n = 44), drawn from a database of 2,116 patients. Patients performed a maximal exercise test on the bicycle until exhaustion before and after an ambulatory exercise training program where exercise training was offered 3 times a week for 3 months. RESULTS Before training, peak oxygen uptake (VO2) was significantly lower in patients with AF compared with the control group (1271 +/- 368 versus 1496 +/- 414 mL/min, P < 0.05). Exercise training significantly increased peak VO2 in both groups (+31%, P < 0.001 in AF and +25%, P < 0.001 in the control group). The gain in peak VO2 did not significantly differ between both groups. A significant decrease in resting heart rate was achieved in both groups after exercise training. AF was also a significant and independent determinant of peak VO2 in the total database, but not of the change in peak VO2. CONCLUSIONS Exercise training significantly improves exercise performance in cardiac patients with AF. AF affects exercise performance but does not impair the beneficial effects of training. Patients with chronic AF should therefore not be dissuaded from participating in exercise training after a cardiac event.

OBJECTIVE—To assess the relation between exercise intensity and oxygen uptake during graded exercise in paediatric patients who underwent surgical repair of congenital heart disease, and to compare it with conventional measures of aerobic exercise function. DESIGN—Cross sectional study. Exercise testing was performed on a treadmill and gas exchange was measured on a breath by breath basis. PATIENTS—29 patients who underwent an atrial switch operation for transposition of the great arteries (TGA) (mean (SD) age at testing 10.3 (2.5) years) and 30 patients who underwent total repair of tetralogy of Fallot (TF) (age 12.1 (3.3) years) performed graded exercise testing. Exercise responses were compared with data obtained in 24 normal controls (age 11.4 (2.6) years). RESULTS—The slope of oxygen uptake versus exercise intensity averaged 1.50 (0.64) ml O2/min2/kg in the patients with TGA and 1.68 (0.75) ml O2/min2/kg after TF repair, both lower (p

Objectives To compare the effects of a highly beta(1)-selective adrenoceptor antagonist bisoprolol with those of atenolol and placebo on endurance exercise capacity in young, healthy male volunteers. Design Twelve subjects randomly received oral placebo, atenolol (100 mg/day) or bisoprolol (10 mg/day) for 3 weeks, following a double-blind cross-over design. Methods At the end of each period, the subjects performed an endurance exercise test on the bicycle ergometer at 70% of maximal aerobic power. Cardiac output was measured by means of an automated CO2-rebreathing method. Venous blood was sampled before, during and after exercise. Results Exercise duration was not significantly different between the two drugs tested. Total exercise duration was significantly reduced by bisoprolol (-19.4 +/- 6.7%, P < 0.01) (mean +/- SEM) and by atenolol (-29.8 +/- 6.6%, P < 0.001), compared with placebo. Atenolol and bisoprolol were equally effective in lowering resting plasma renin activity, heart rate and systolic blood pressure. Resting and exercise stroke volume were significantly increased by both drugs, so that cardiac output was not significantly affected. Both drugs induced significant decreases in plasma-free fatty acid concentrations during recovery and blunted the exercise-induced increase. There were no significant relationships between the reduction of exercise duration and the haemodynamic changes or the degree of impairment of the exercise-induced increase in free fatty acid release resulting from beta-blockade. Conclusions It is concluded that both drugs affect endurance exercise capacity in young, normotensive men, with a tendency to a smaller reduction during bisoprolol treatment. Haemodynamic variables are unlikely to be involved in the reduction of endurance exercise capacity. The role of the reduced availability of plasma free fatty acids remains unclear. J Hypertens 2000, 18:35-43 (C) Lippincott Williams & Wilkins.

In coronary artery disease (CAD) the individual variation in aerobic power and the response to physical training are largely unexplained.1 The gene coding for the angiotensin converting enzyme (ACE) is expressed in several types of somatic cells, including vascular cells, heart, lung, and muscles.2 Intron 16 contains a polymorphism characterised by the presence (insertion (I)) or absence (deletion (D)) of a 287 bp Alu repeat sequence,3 which has been associated with endurance related phenotypes and the response to training.4 The objective of the present study was to investigate the role of ACE I/D polymorphism on aerobic power and its response to physical training in patients with CAD enrolled in the CAREGENE (cardiac rehabilitation and genetics of exercise performance) study. Biologically unrelated white patients with CAD (mean (SE) age 56 (0.3) years) who had achieved evident exhaustion during graded cycle ergometer testing before and after three months of physical training (three sessions weekly) from 1990 through 2001 (n = 1095) were eligible for inclusion. The methods for graded exercise testing and training have been …