Diminished mitochondrial oxidative phosphorylation and aerobic capacity are associated with reduced longevity. We tested whether resveratrol (RSV), which is known to extend lifespan, impacts mitochondrial function and metabolic homeostasis. Treatment of mice with RSV significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1alpha acetylation and an increase in PGC-1alpha activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1(-/-) MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.

The objectives of this study were to evaluate the reliability and accuracy of a new impedance cardiograph device, the Physio Flow, at rest and during a steady-state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in the supine position. We compared cardiac output determined simultaneously by two methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty patients referred for right cardiac catheterisation, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease, took part in this study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(-1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(-1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34, +2.92 l x min(-1) during exercise. The difference between the two methods exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio Flow provides a clinically acceptable and non-invasive evaluation of cardiac output under these conditions. This new impedance cardiograph device deserves further study using other populations and situations.

The goal of the study was to determine the effects of continuous (CT) vs. intermittent (IT) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects. Eleven subjects (6 men and 5 women, 45 +/- 3 years) were randomly assigned to either of the two 8-wk training programs in a cross-over design, separated by 12 wk of detraining. Maximal oxygen uptake (Vo2max) increased after both trainings (9% with CT vs. 15% with IT), whereas only IT was associated with faster Vo2 kinetics (tau: 68.0 +/- 1.6 vs. 54.9 +/- 0.7 s, P < 0.05) measured during a test to exhaustion (TTE) and with improvements in maximal cardiac output (Qmax, from 18.1 +/- 1.1 to 20.1 +/- 1.2 l/min; P < 0.01). Skeletal muscle mitochondrial oxidative capacities (Vmax) were only increased after IT (3.3 +/- 0.4 before and 4.5 +/- 0.6 micromol O2 x min(-1) x g dw(-1) after training; P < 0.05), whereas capillary density increased after both trainings, with a two-fold higher enhancement after CT (+21 +/- 1% for IT and +40 +/- 3% after CT, P < 0.05). The gain of Vmax was correlated with the gain of TTE and the gain of Vo2max with IT. The gain of Qmax was also correlated with the gain of VO2max. These results suggest that fluctuations of workload and oxygen uptake during training sessions, rather than exercise duration or global energy expenditure, are key factors in improving muscle oxidative capacities. In an integrative view, IT seems optimal in maximizing both peripheral muscle and central cardiorespiratory adaptations, permitting significant functional improvement. These data support the symmorphosis concept in sedentary subjects.

Our findings identify statins as a new activating factor of cardiac mitochondrial biogenesis and antioxidant capacities, and suggest the importance of ROS/PGC-1 signalling pathway as a key element in regulation of mitochondrial function in cardiac as well as skeletal muscles.

. This first systematic literature review confirms the rarity of IM and may highlight certain genetic and environmental determinants of IM. There is a need for uniformity in diagnostic and classification criteria as well as more exhaustive case ascertainment to refine IM epidemiology.

One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.

This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak ◊ O 2 , expressed in ml min _1 kg _1 ). All volunteers underwent a cyclo-ergometric incremental exercise test to estimate their peak ◊ O 2 and ◊ O 2 at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (◊ 0 ) or in the presence (◊ max ) of saturating [ADP]. While ◊ 0 was similar, ◊ max differed among groups (sedentary, 3.7 ± 0.3, active, 5.9 ± 0.9 and athletic, 7.9 ± 0.5 mmol O 2 min _1 (g dry weight) _1). ◊ max was correlated with peak ◊ O 2 (P < 0.01, r = 0.63) and with ◊ T (P < 0.01, r = 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (◊ max /◊ 0 ) in the athletic individuals. The mitochondrial K m for ADP was significantly higher in athletic subjects (P < 0.01). Mitochondrial CK (mi-CK) activation by addition of creatine induced a marked decrease in K m in athletic individuals only, indicative of an efficient coupling of mi-CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co-ordination of energy fluxes by CK for higher efficacy.

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