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Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated. Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0–45th min) and with PEP = 10 cmH2O (PEP10, 46–90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10. Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (−16 ± 14 cm.s–1) and cardiac output (−0.7 ± 1.2 L.min–1) together with a reduced stroke volume (−9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (−1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043). Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

Background. In this study (the first of two related papers), we report whether the relationship between the demographic and anthropometric variables (DA, i.e. age, gender, height and weight) employed in current creatinin (Cr)-based glomerular filtration rate (GFR) estimation equations and actual GFR is mediated by muscle mass. Methods. We studied 77 patients (mean age ± SD, 65.1 ± 11.9 years) with chronic kidney disease (mean GFR 45.7 ± 28.6 ml/ min/1.73 m2). Actual GFR was measured by the renal clearance of inulin (GFRinu). Appendicular lean mass (ALM) and its index (ALMI) by dual energy X-ray absorptiometry provided markers of muscle mass. Multiple regression analyses identified variables explaining variance in (i) GFR, (ii) ALM and (iii) Cr. Results. (i) The DA variables used in the abbreviated modification of diet in renal disease (MDRD) equation accounted for only 59.6% (P < 0.001) of the variance in GFRinu, whilst adding ALM explained an additional 10.4% variance (P < 0.001). If ALMI was entered first, the relationship between DA variables and GFRinu was reduced (for weight) or completely abolished (for age, gender and height). (ii) After inputting all the commonly used DA variables, 17.2% of the variance in ALM was unexplained. (iii) All the DA variables explained only 60.6% (P < 0.001) of the variance in Cr, whilst adding ALM explained an additional 4.2% variance (P < 0.005). Conclusions. Muscle mass explained more variance in GFRinu than MDRD DA variables and mediated the relationship between GFRinu and DA variables. Furthermore, DA variables failed to account for individual differences in muscle mass or Cr. Consequently, there is a need to validate simpler, clinically obtainable measures of muscle mass and determine whether these measures will improve GFR estimation. © Copyright 2006 Oxford University Press.

Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients. Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-α (TNF-α) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting. Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 ± 0.9 versus 21.5 ± 1.5 kg, P

Background: Fatigue is one of the most prevalent symptoms in chronic kidney disease (CKD). However, fatigue mechanisms are poorly understood due in part to nonspecific definitions. This study investigates exertional fatigue during simulated activities of daily living, focusing on oxygen delivery and utilization. Study Design: "Explanatory" matched-cohort study. Participants & Setting: 13 patients with CKD (stages 3b-4; mean age, 62 ± 13 [SD] years) and 13 healthy controls, mean matched for age, height, body mass and composition, and physical activity level. Participants completed an incremental cycle ergometer test to simulate energy expenditure of typical activities of daily living. Factor: 4 exercise intensities: 1, 1.8, 2.4, and 3.1 metabolic equivalent tasks (METs). Outcomes: The primary outcome was exertional fatigue by rating of perceived exertion (RPE) on a 6-20 scale. Measurements: Other multidimensional measures of fatigue: UK Short Form Health Survey 36 (UK SF-36) Vitality and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) subscales. Physiologic measures of the oxygen transport and utilization chain (expired gas analysis, cardiac output, and arterial oxygen content) and blood lactate. Results: RPE was increased in patients compared with controls at 2.4 (10.5 [ie, light] ± 2.7 vs 8.7 [very light] ± 1.7 units) and 3.1 (12.5 [somewhat hard] ± 2.6 vs 10.2 [light] ± 1.7 units) METs (interaction P = 0.03), which was consistent with higher chronic fatigue in patients by both the UK SF-36 Vitality (P = 0.01) and FACIT-Fatigue (P = 0.004) subscales. Arterial oxygen content was decreased in patients (P = 0.001), but cardiac output and oxygen extraction ratio were unchanged, decreasing oxygen delivery (P = 0.04). Respiratory exchange ratio (P = 0.004) and blood lactate production (P = 0.002) were increased. Limitations: Those inherent to a matched-cohort study. Conclusions: Using a novel application of the outcome measure RPE, patients with non-dialysis-dependent CKD reported considerable exertional fatigue during simulated activities of daily living. Poor compensation for mild anemia contributed to this symptom. In addition to anemia, the entire oxygen transport chain needs to be targeted to treat fatigue in patients with CKD. © 2012 National Kidney Foundation, Inc.

Haemodialysis (HD) patients are characterized by muscle wasting and consequently decreased physical functioning and poor outcome. This pilot study investigated if a novel intradialytic exercise programme could increase lean mass via up-regulation of the insulin-like growth factor (IGF) system. Nine HD patients were assessed before (w-12) and after a 3-month control phase (w0), after a three-month intradialytic interval training programme using high intensity cycle exercise (w12), and after a withdrawal of treatment phase (w24). Body composition was determined by dual energy X-ray absorptiometry (DEXA) and bioelectrical impedance spectroscopy (BIS); physical functioning by knee extensor strength (KES) and 30-s sit stand test (SST); and IGF-I and IGFBP-3 in serum and muscle by radioimmunoassay. Despite significant increases in training load (+274%, P