Prognostic value of resting end-tidal carbon dioxide in patients with heart failure

Background: Cardiopulmonary exercise testing (CPET) variables provide valuable prognostic information in the heart failure (HF) population. The purpose of the present study is to assess the ability of resting end-tidal carbon dioxide partial pressure (PETCO2) to predict cardiac-related events in patients with HF. Methods: 121 subjects diagnosed with compensated HF under-went CPET on an outpatient basis. Mean age and ejection fraction were 49.3 years (+/- 14.7) and 28.4% (+/- 13.4), respectively. Resting P(ET)CO2 was determined immediately prior to the exercise test in the seated position. Peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production (VE/VCO2) slope were also acquired during CPET. Results: There were 41 cardiac-related hospitalizations and 9 cardiac-related deaths in the year following CPET. Mean resting PETCO2, peak VO2 and VE/VCO2 slope were 34.1 mmHg (+/- 4.6), 14.5 ml(.)kg(-1.)min(-1) (+/- 5.1) and 35.9 (+/- 8.7) respectively. Univariate Cox regression analysis revealed that resting PETCO2 (Chi-square=28.4, p < 0.001), peak VO2 (Chi-square=21.6, p < 0.001) and VE/VCO2 slope (Chisquare=54.9, p < 0.001) were all significant predictors of cardiac related events. Multivariate Cox regression analysis revealed resting PETCO2 added to the prognostic value of VE/VCO2 Slope in predicting cardiac related events (residual Chi-square=4.4, p=0.04). Peak VO2 did not add additional value and was removed (residual Chi-square=3.2, p=0.08). Conclusions: These results indicate a resting ventilatory expired gas variable possesses prognostic value independently and in combination with an established prognostic marker from the CPET. Resting PETCO2 may therefore be a valuable objective measure to obtain during both non-exercise and exercise evaluations in patients with HF

Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work

PURPOSE: We explored whether altered expression of factors tuning mitochondrial metabolism contributes to muscular adaptations with endurance training in the condition of lowered ambient oxygen concentration (hypoxia) and whether these adaptations relate to oxygen transfer as reflected by subsarcolemmal mitochondria and oxygen metabolism in muscle. METHODS: Male volunteers completed 30 bicycle exercise sessions in normoxia or normobaric hypoxia (4,000 m above sea level) at 65 % of the respective peak aerobic power output. Myoglobin content, basal oxygen consumption, and re-oxygenation rates upon reperfusion after 8 min of arterial occlusion were measured in vastus muscles by magnetic resonance spectroscopy. Biopsies from vastus lateralis muscle, collected pre and post a single exercise bout, and training, were assessed for levels of transcripts and proteins being associated with mitochondrial metabolism. RESULTS: Hypoxia specifically lowered the training-induced expression of markers of respiratory complex II and IV (i.e. SDHA and isoform 1 of COX-4; COX4I1) and preserved fibre cross-sectional area. Concomitantly, trends (p < 0.10) were found for a hypoxia-specific reduction in the basal oxygen consumption rate, and improvements in oxygen repletion, and aerobic performance in hypoxia. Repeated exercise in hypoxia promoted the biogenesis of subsarcolemmal mitochondria and this was co-related to expression of isoform 2 of COX-4 with higher oxygen affinity after single exercise, de-oxygenation time and myoglobin content (r ≥ 0.75). Conversely, expression in COX4I1 with training correlated negatively with changes of subsarcolemmal mitochondria (r < -0.82). CONCLUSION: Hypoxia-modulated adjustments of aerobic performance with repeated muscle work are reflected by expressional adaptations within the respiratory chain and modified muscle oxygen metabolism

Age, muscle fatigue, and walking endurance in pre-menopausal women

Aging is associated with loss of endurance; however, aging is also associated with decreased fatigue during maximal isometric contractions. The aims of this study were to examine the relationship between age and walking endurance (WE) and maximal isometric fatigue (MIF) and to determine which metabolic/fitness components explain the expected age effects on WE and MIF. Subjects were 96 pre-menopausal women. Oxygen uptake (walking economy) was assessed during a 3-mph walk; aerobic capacity and WE by progressive treadmill test; knee extension strength by isometric contractions, MIF during a 90-s isometric plantar flexion (muscle metabolism measured by 31P MRS). Age was related to increased walking economy (low VO2, r = −0.19, P 0.80). In premenopausal women, age is related to WE and MIF. In addition, these results support the hypothesis that age-related increases in metabolic economy may decrease MIF. However, decreased muscle strength and oxidative capacity are related to WE