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.

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.

We examined the transcriptional signaling cascade involved in the changes of mitochondrial biogenesis and mitochondrial function of skeletal muscle and of the exercise capacity of humans in response to long-term physical activity and chronic heart failure (CHF). Biopsy samples of vastus lateralis muscle were obtained from 18 healthy subjects with different fitness levels (assessed by maximal oxygen uptake, VO2 peak). We compared 9 sedentary subjects with 10 CHF patients undergoing transplantation. Muscle oxidative capacity was measured in permeabilized fibers (Vmax). Transcript levels of target genes were quantified by RT-PCR. In healthy subjects, VO2 peak was linearly related to Vmax (P<0.01) and to the gene expression of mitochondrial proteins and of the coactivator PGC-1alpha and its downstream transcription factors. A coordinate increase in PGC-1alpha and mRNA levels of proteins involved in degradation, fusion, and fission of mitochondria was observed associated with calcineurin activation. Despite decreased VO2 peak, in CHF patients skeletal muscles showed preserved Vmax in accordance with preserved markers and transcription factors of mitochondrial biogenesis and dynamics, with no calcineurin activation. The results provide strong support for a central role for PGC-1alpha and calcineurin activation in mitochondrial biogenesis in healthy and diseased human skeletal muscles.

In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.