Acute resveratrol supplementation in coronary artery disease: towards patient stratification.

Objective: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients. Design: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results: RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS). Conclusion: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III).

The beneficial effect of exercise training and exercise-based cardiac rehabilitation on symptom-free exercise capacity,cardiovascular and skeletal muscle function, quality of life, general healthy lifestyle, and reduction of depressive symptoms and psychosocial stress is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity (PA) and exercise training--frequency, intensity, time (duration), type (mode), and volume (dose: intensity x duration) of exercise--are the most effective. The present paper, therefore, will deal with these exercise characteristics in the management of individuals with cardiovascular disease, i.e. coronary artery disease and chronic heart failure patients, but also in patients with congenital or valvular heart disease. Based on the current literature, and if sufficient evidence is available, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding frequency, intensity, time and type of PA, and safety aspects during exercise inpatients with cardiovascular disease. This paper is the third in a series of three papers, all devoted to the same theme: the importance of the exercise characteristics in the management of cardiovascular health. Part I is directed to the general population and Part II to individuals with cardiovascular risk factors. In general, PA recommendations and exercise training programmes for patients with coronary artery disease or chronic heart failure need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible and to perform endurance exercise training 30­60 min daily (3­5 days per week) in combination with resistance training 2­3 times a week. Because of the frequently reported dose­response relationship between training effect and exercise intensity, one should seek sufficiently high training intensities, although more scientific evidence on effect sizes and safety is warranted. At present, there is insufficient data to give more specific recommendations on type, dosage, and intensity of exercise in some other cardiovascular diseases, such as congenital heart disease, valve disease, cardiomyopathies, channelopathies, and patients with implanted devices.

Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I).

Over the last decades, more and more evidence is accumulated that physical activity (PA) and exercise interventions are essential components in primary and secondary prevention for cardiovascular disease. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit in achieving cardiovascular health. The present paper, as the first of a series of three, will make specific recommendations on the importance of these characteristics for cardiovascular health in the population at large. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and the individual member of the public. Based on previous and the current literature, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and exercise.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial.

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; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). 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.

Reproducibility of energy cost of locomotion in ambulatory children with spina bifida.

OBJECTIVES: Many ambulatory children with Spina Bifida (SB) experience functional decline in ambulation despite stable or even improving motor exams. Improving or maintaining low energy cost of locomotion during childhood and throughout the teenage years, could be an important goal for children and adolescents with SB. Purpose of this study was to determine reproducibility of energy expenditure measures during gait in ambulatory children with SB. DESIGN: Reproducibility study. SETTING: Child Development and Exercise Center of the University Children's Hospital in Utrecht, the Netherlands. PARTICIPANTS: Fourteen ambulatory children (6 boys/8 girls) with SB. Mean age was 10.8 years (+ or - 3.4). INTERVENTIONS: Net and gross energy expenditure measures during locomotion were determined during a six-minute walking test. These measures consisted of energy consumption (ECS), expressed in J/kg/min, and energy cost (EC), expressed in J/kg/m. For reliability, the intra-class coefficient (ICC) was determined. For agreement, the smallest detectable difference (SDD) was calculated. RESULTS: ICCs vary from 0.86 to 0.96 for both EC and ECS. The SDD ranges from 18-24% for gross measures, up to over 30% for net values. CONCLUSION: Reproducibility of energy expenditure during ambulation in children with SB should be considered carefully when using these measures in the evaluation of gait. High reliability of energy expenditure measurements makes these measurements appropriate to use as discriminative tools in children with SB, while agreement of only gross EC seems acceptable to use as a evaluative tool in children with SB. Overall, measures of reliability and agreement seem higher in young children when compared to adolescents. Further research is recommended to determine clinically relevant changes in energy expenditure in children with SB.

Limiting factors in peak oxygen uptake and the relationship with functional ambulation in ambulating children with spina bifida.

The objective of this study is to interpret the outcomes of peak oxygen uptake (VO(2peak)) in children with SB and explore the relationship between VO(2peak) and functional ambulation using retrospective cross-sectional study. Twenty-three ambulating children with SB participated at Wilhelmina's Children's Hospital Utrecht, the Netherlands. VO(2peak) was measured during a graded treadmill-test. Eschenbacher's and Maninna's algorithm was used to determine limiting factors in reaching low VO(2peak) values. Energy expenditure during locomotion (both O(2) rate and O(2) cost) and percentage of VO(2peak) and HR(peak) were determined during a 6-min walking test (6MWT). Differences between community and normal ambulators were analyzed. VO(2peak), VO(2peak)/kg, HR(peak), RER(peak) and VE (peak) were significantly lower compared to reference values, with significant differences between normal and community ambulators. Limiting factors according to the algorithm were mostly "muscular and/or deconditioning" (47%) and ventilatory "gasexchange" (35%). Distance walked during 6MWT was 48.5% of predicted distance. Both O(2) rate and O(2) cost were high with significant differences between normal and community ambulators [17.6 vs. 21.9 ml/(kg min) and 0.27 vs 0.43 ml/(kg m)]. Also %HR(peak) and %VO(2peak) were significantly higher in community ambulators when compared to normal ambulators (resp. 97.6 vs. 75% and 90.2 vs. 55.9%). VO(2peak) seems to be mostly limited by deconditioning and/or muscular components and possible ventilatory factors. For both peak values and functional ambulation, community ambulators were significantly more impaired than normal ambulators. High energy expenditure, %VO(2peak) and %HR(peak) reflect high level of strain during ambulation in the community ambulators. Future exercise testing in children with SB should include assessment of ventilatory reserve. Exercise training in ambulatory children should focus on increasing both VO(2peak) and muscular endurance, as well as decreasing energy cost of locomotion.

Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment.

BACKGROUND: Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Studies in which activity, fitness and cognition are reported in the same individuals could help to resolve this question. OBJECTIVES: To assess the effectiveness of physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without known cognitive impairment. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PEDro, SPORTDiscus, PsycINFO, CINAHL, Cochrane Controlled Trials Register (CENTRAL), Dissertation abstracts international and ongoing trials registers on 15 December 2005 with no language restrictions. SELECTION CRITERIA: All published randomised controlled trials comparing aerobic physical activity programmes with any other intervention or no intervention with participants older than 55 years of age were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eleven RCTs fulfilling the inclusion criteria are included in this review. Two reviewers independently extracted the data from these included studies. MAIN RESULTS: Eight out of 11 studies reported that aerobic exercise interventions resulted in increased cardiorespiratory fitness of the intervention group (an improvement on the maximum oxygen uptake test which is considered to be the single best indicator of the cardiorespiratory system) of approximately 14% and this improvement coincided with improvements in cognitive capacity. The largest effects on cognitive function were found on motor function, auditory attention and delayed memory functions (effect sizes of 1.17, 0.52 and 0.50 respectively). However, the results for delayed memory functions should be interpreted with care since they are based on a single study. Moderate effects were observed for cognitive speed (speed at which information is processed; effect size 0.26) and visual attention (effect size 0.26). AUTHORS' CONCLUSIONS: There is evidence that aerobic physical activities which improve cardiorespiratory fitness are beneficial for cognitive function in healthy older adults, with effects observed for motor function, cognitive speed, delayed memory functions and auditory and visual attention. However, the majority of comparisons yielded no significant results. The data are insufficient to show that the improvements in cognitive function which can be attributed to physical exercise are due to improvements in cardiovascular fitness, although the temporal association suggests that this might be the case. Larger studies are still required to confirm whether the aerobic training component is necessary, or whether the same can be achieved with any type of physical exercise. At the same time, it would be informative to understand why some cognitive functions seem to improve with (aerobic) physical exercise while other functions seem to be insensitive to physical exercise. Clinicians and scientists in the field of neuropsychology should seek mutual agreement on a smaller battery of cognitive tests to use, in order to render research on cognition clinically relevant and transparent and heighten the reproducibility of results for future research.

Oxygen uptake efficiency slope in coronary artery disease: clinical use and response to training.

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.

Changes in QRS duration are associated with maximal exercise capacity in adult patients with repaired tetralogy of Fallot.

OBJECTIVE: In adult patients with repaired tetralogy of Fallot (TF) QRS duration at rest seems to be a predictor of maximal exercise. We examined the relationship between QRS duration during exercise and exercise performance. DESIGN: In 57 consecutive TF patients QRS duration in V1 (ms) was measured at rest, at maximal exercise (Wmax, W), and at peak oxygen consumption (peak VO2, ml/min). Stroke volume (SV) was calculated from cardiac output, obtained by CO2 rebreathing. Spearman rank correlation was used to describe the relationship between QRS duration and exercise performance. Statistical significance was defined as P<0.05. RESULTS: Seven patients, who didn't pass the anaerobic threshold, and one outlier (Wmax=340 W) were excluded, resulting in a sample of 49 patients (75.5% male; median age=24 years, range 16-43 years). QRS duration at rest (median=160 ms, range 78-194 ms) and at maximal exercise (median=153 ms, range 80-193 ms) did not differ significantly. The median change of QRS duration during exercise was -5 ms (range -31 to +83 ms). This was negatively correlated with Peak VO2 (2081+/-577 ml/min; rho=-0.33, P=0.02) and Wmax (182+/-53 Watt; rho=-0.33, P=0.02). In patients with QRS shortening peak VO2 and the exercise induced increase in SV were significantly higher than in patients with QRS shortening. CONCLUSIONS: This study indicates that QRS shortening during exercise in TF patients is related with a better exercise performance. Lower increase in stroke volumes may be responsible for this difference. Further research is needed to elaborate these findings.

Physical activity for primary and secondary prevention. Position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

There is now clear scientific evidence linking regular aerobic physical activity to a significant cardiovascular risk reduction, and a sedentary lifestyle is currently considered one of the five major risk factors for cardiovascular disease. In the European Union, available data seem to indicate that less than 50% of the citizens are involved in regular aerobic leisure-time and/or occupational physical activity, and that the observed increasing prevalence of obesity is associated with a sedentary lifestyle. It seems reasonable therefore to provide institutions, health services, and individuals with information able to implement effective strategies for the adoption of a physically active lifestyle and for helping people to effectively incorporate physical activity into their daily life both in the primary and the secondary prevention settings. This paper summarizes the available scientific evidence dealing with the relationship between physical activity and cardiovascular health in primary and secondary prevention, and focuses on the preventive effects of aerobic physical activity, whose health benefits have been extensively documented.

Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial.

OBJECTIVE: To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington's disease (HD). METHODS: A 1-year double-blind placebo-controlled study was performed in 41 patients with HD (stage I through III). At baseline and after 6 and 12 months, the functional, neuromuscular, and cognitive status of the patients was assessed by a test battery that consisted of 1) the Unified Huntington's Disease Rating Scale (UHDRS), 2) an exercise test on an isokinetic dynamometer to assess strength of the elbow flexor muscles, 3) a maximal exercise test on a bicycle ergometer to evaluate cardiorespiratory fitness, and 4) a test to assess bimanual coordination ability. Following the baseline measurements, the subjects were assigned to either a creatine (n = 26) or a placebo group (n = 15). RESULTS: Scores on the functional checklist of the UHDRS (p < 0.05), maximal static torque (p < 0.05), and peak oxygen uptake (p < 0.05) decreased from the start to the end of the study, independent of the treatment received. Cognitive functioning, bimanual coordination ability, and general motor function (total motor scale, UHDRS) did not change from baseline to 1 year in either group. CONCLUSION: One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromuscular, and cognitive status in patients with stage I to III HD.

High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification.

BACKGROUND: Electrocardiographic abnormalities and premature ventricular contractions are common in athletes and are generally benign. However, the specific outcome of high-level endurance athletes with frequent and complex ventricular arrhythmias is unclear. Also, information on the predictive accuracy of different investigations in this subgroup is unknown. RESULTS: We report on 46 high-level endurance athletes with ventricular arrhythmias (45 male; median age 31 years) followed-up for a median of 4.7 years. Eighty percent were cyclists. Hypertrophic cardiomyopathy or coronary abnormalities were present in < or =5%. Eighty percent of the arrhythmias had a left bundle branch morphology. Right ventricular (RV) arrhythmogenic involvement (based on a combination of multiple criteria) was manifest in 59% of the athletes, and suggestive in another 30%. Eighteen athletes developed a major arrhythmic event (sudden death in nine, all cyclists). They were significantly younger than those without event (median 23 years vs 38 years; P=0.01). Outcome could not be predicted by presenting symptoms, non-invasive arrhythmia evaluation or morphological findings at baseline. Only the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during invasive electrophysiological testing was significantly related to outcome (RR 3.4; P=0.02). Focal arrhythmias were associated with a better prognosis than those due to reentry (P=0.02) but the mechanism could be determined in only 22 (48%). CONCLUSIONS: Complex ventricular arrhythmias do not necessarily represent a benign finding in endurance athletes. An electrophysiological study is indicated for risk evaluation, both by defining inducibility and identifying the arrhythmogenic mechanism. Endurance athletes with arrhythmias have a high prevalence of right ventricular structural and/or arrhythmic involvement. Endurance sports seems to be related to the development and/or progression of the underlying arrhythmogenic substrate.

Secondary prevention through cardiac rehabilitation: position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

The purpose of this statement is to provide specific recommendations in regard to evaluation and intervention in each of the core components of cardiac rehabilitation (CR) to assist CR staff in the design and development of their programmes; the statement should also assist health care providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of such programmes. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, at national or at individual centre level, need to consider where and how structured programmes of CR can be delivered to the large constituency of patients now considered eligible for CR.

Exercise performance and training in patients with implantable cardioverter-defibrillators and coronary heart disease.

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.

Twenty-four hour blood pressure after exercise in patients with coronary artery disease.

The objective was to assess the influence of a cardiac rehabilitation training session on blood pressure measured shortly after exercise and during the subsequent 24 h in patients with stable coronary artery disease. Blood pressure was measured conventionally and by use of 24-h ambulatory blood pressure monitoring in seven men, mean age 53+/-8 (s.d.) years, after participation in a cardiac rehabilitation session and, in randomised order, on a non-exercise control day. Conventional blood pressure averaged 112+/-7/77+/-5 mm Hg in the sitting position on the control day and was not different at the same time of the day shortly after the patients had participated in a cardiac rehabilitation training session. Standing systolic pressure was lower by 7.8+/-4.3 mm Hg (P < 0.005) after exercise compared to the control situation, but this was not associated with orthostatic symptoms. However, ambulatory monitoring showed no differences in blood pressure with the non-exercise day during the subsequent 24-h period. In conclusion, standing but not sitting blood pressure was slightly lower shortly after a cardiac rehabilitation session, but the postexercise orthostatic hypotension was not sustained during normal activities of daily living.

Comparison of cardiac output measured by two automated methods of CO2 rebreathing.

PURPOSE: 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. METHODS: 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. RESULTS: 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 (P < or = 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, P < or = 0.001). The equilibrium method produced unpleasant side effects more frequently (75% vs 21%, P < or = 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). CONCLUSIONS: 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.