Stability of heartbeat interval distributions in chronic high altitude hypoxia

Recent studies of nonlinear dynamics of the long-term variability of heart rate have identified nontrivial long-range correlations and scale-invariant power-law characteristics (1/f noise) that were remarkably consistent between individuals and were unrelated to external or environmental stimuli (Meyer et al., 1998a). The present analysis of complex nonstationary heartbeat patterns is based on the sequential application of the wavelet transform for elimination of local polynomial nonstationary behavior and an analytic signal approach by use of the Hilbert transform (Cumulative Variation Amplitude Analysis). The effects of chronic high altitude hypoxia on the distributions and scaling functions of cardiac intervals over 24 hr epochs and 4 hr day/nighttime subepochs were determined from serial heartbeat interval time series of digitized 24 hr ambulatory ECGs recorded in 9 healthy subjects (mean age 34 yrs) at sea level and during a sojourn at high altitude (5,050 m) for 34 days (Ev-K2-CNR Pyramid Laboratory, Sagarmatha National Park, Nepal). The results suggest that there exists a hidden, potentially universal, common structure in the heterogeneous time series. A common scaling function with a stable Gamma distribution defines the probability density of the amplitudes of the fluctuations in the heartbeat interval time series of individual subjects. The appropriately rescaled distributions of normal subjects at sea level demonstrated stable Gamma scaling consistent with a single scaled plot (data collapse). Longitudinal assessment of the rescaled distributions of the 24 hr recordings of individual subjects showed that the stability of the distributions was unaffected by the subject's exposure to a hypobaric (hypoxic) environment. The rescaled distributions of 4 hr subepochs showed similar scaling behavior with a stable Gamma distribution indicating that the common structure was unequivocally applicable to both day and night phases and, furthermore, did not undergo systematic changes in response to high altitude. In contrast, a single function stable over a wide range of time scales was not observed in patients with congestive heart failure or patients after cardiac transplantation. The functional form of the scaling in normal subjects would seem to be attributable to the underlying nonlinear dynamics of cardiac control. The results suggest that the observed Gamma scaling of the distributions in healthy subjects constitutes an intrinsic dynamical property of normal heart function that would not undergo early readjustment or late acclimatization to extrinsic environmental physiological stress, e.g., chronic hypoxi

Is the heart preadapted to hypoxia? Evidence from fractal dynamics of heartbeat interval fluctuations at high altitude (5,050 m)

The dynamics of heartbeat interval time series over large time scales were studied by a modifed random walk analysis introduced recently asDetrended Fluctuation Analysis. In this analysis, the intrinsic fractal long-range power-law correlation properties of beat-to-beat fluctuations generated by the dynamical system (i.e., cardiac rhythm generator), after decomposition from extrinsic uncorrelated sources, can be quantified by the scaling exponent (α) which, in healthy subjects, for time scales of ∼104 beats is ∼1.0. The effects of chronic hypoxia were determined from serial heartbeat interval time series of digitized twenty-four-hour ambulatory ECGs recorded in nine healthy subjects (mean age thirty-four years old) at sea level and during a sojourn at 5,050 m for thirty-four days (Ev-K2-CNR Pyramid Laboratory, Sagarmatha National Park, Nepal). The group averaged α exponent (±SD) was 0.99±0.04 (range 0.93-1.04). Longitudinal assessment of α in individual subjects did not reveal any effect of exposure to chronic high altitude hypoxia. The finding of α∼1 indicating scale-invariant long-range power-law correlations (1/f noise) of heartbeat fluctuations would reflect a genuinely self-similar fractal process that typically generates fluctuations on a wide range of time scales. Lack of a characteristic time scale along with the absence of any effect from exposure to chronic hypoxia on scaling properties suggests that the neuroautonomic cardiac control system is preadapted to hypoxia which helps prevent excessive mode-locking (error tolerance) that would restrict its functional responsiveness (plasticity) to hypoxic or other physiological stimul

Diversity of human skeletal muscle in health and disease: contribution of proteomics

Muscle represents a large fraction of the human body mass. It is an extremely heterogeneous tissue featuring in its contractile structure various proportions of heavy- and light-chain slow type 1 and fast types 2A and 2X myosins, actins, tropomyosins, and troponin complexes as well as metabolic proteins (enzymes and most of the players of the so-called excitation-transcription coupling). Muscle is characterized by wide plasticity, i.e. capacity to adjust size and functional properties in response to endogenous and exogenous influences. Over the last decade, proteomics has become a crucial technique for the assessment of muscle at the molecular level and the investigation of its functional changes. Advantages and shortcomings of recent techniques for muscle proteome analysis are discussed. Data from differential proteomics applied to healthy individuals in normal and unusual environments (hypoxia and cold), in exercise, immobilization, aging and to patients with neuromuscular hereditary disorders (NMDs), inclusion body myositis and insulin resistance are summarized, critically discussed and, when required, compared with homologous data from pertinent animal models. The advantages as well as the limits of proteomics in view of the identification of new biomarkers are evaluate

Asymmetric vortex merger: mechanism and criterion

The merging of two unequal co-rotating vortices in a viscous fluid is investigated. Two-dimensional numerical simulations of initially equal sized Lamb-Oseen vortices with differing relative strengths are performed. Results show how the disparity in deformation rates between the vortices alters the interaction. Key physical mechanisms associated with vortex merging are identified. A merging criterion is formulated in terms of the relative timing of core detrainment and destruction. A critical strain parameter is defined to characterize the establishment of core detrainment. This parameter is shown to be directly related to the critical aspect ratio in the case of symmetric merger

The point of maximum curvature as a marker for physiological time series

We present a geometric analysis of the model of Stirling. In particular we analyze the curvature of a heart rate time series in response to a step like increment in the exercise intensity. We present solutions for the point of maximum curvature which can be used as a marker of physiological interest. This marker defines the point after which the heart rate no longer continues to rapidly rise and instead follows either a steady state or slow rise. These methods are then applied to find analytic solutions for a mono exponential model which is commonly used in the literature to model the response to a moderate exercise intensity. Numerical solutions are then found for the full model and parameter values presented in Stirling

EFFECTS OF ACUTE OR CHRONIC HYPOXIA ON REACTIVE OXYGEN SPECIES PRODUCTION ASSESSED BY ELECTRON PARAMAGNETIC RESONANCE

There is indirect evidence from cells and tissue experiments that acute hypoxia induces accumulation of reactive oxygen species (ROS). This is also the case for the whole body of animals and man as appears from muscle proteomic analysis. Electronic Paramagnetic Resonance (EPR) is the only non-invasive technique available to detect and quantitate ROS accumulation. By means of a recently developed EPR Scanner (Bruker e-scan) suitable for 50 \uecl sample analysis and sensitive to very low (nM) concentration levels, the time course of ROS in capillary blood could be monitored: a) in sedentary subjects (n=6) at the onset (square wave), during and after 2-4 h of acute hypoxic exposure (equivalent to 4500 meters a. s.l.); b) in athletes (n=18) before and after 2wk exposure to moderate altitude (1860m). The data were compared with complementary enzymatic assays of Protein Carbonyls, PC and ThioBarbituric Acid Reactive Substances, TBARS. Results: In (a), a fast, initial elevation of ROS was observed, whose size appears to be related to the subjects\u2019 capillary PO2, followed within 2 h by a return to pre-hypoxia levels. Parenthetically, plasmatic concentrations of TBARS and PC were significantly increased after 4 h of hypoxia exposure and up to 1 h into recovery, then resuming pre-hypoxia levels within 8 h; (b) two weeks exposure to moderate hypoxia induced significant increases in both ROS and oxidative markers concentration. The experimental conditions under investigation, even though very different for degree of hypoxia and duration, were both characterized by comparable accumulation of ROS and oxidative damage

J Musculoskelet Neuronal Interact

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed

Abnormal blood flow in the sublingual microcirculation at high altitude

We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas. Microcirculatory flow index (MFI) was calculated from the moving images of microcirculatory red blood cell flow, and comparison was made between the baseline and high altitude measurements. Peripheral oxygen saturation (SpO2) and Lake Louise scores (LLS) were recorded along with MFI. Our data demonstrate that there was a significant reduction in MFI from baseline to 4,900 m in small (less than 25 μm) and medium (26–50 μm) sized blood vessels (P = 0.025 and P = 0.046, respectively). There was no significant correlation between MFI and SpO2 or MFI and LLS. Disruption of blood flow within microcirculatory may explain persistent abnormal oxygen flux to tissues following the normalisation of systemic oxygen delivery that accompanies acclimatisation to high altitude

TCA cycle rewiring fosters metabolic adaptation to oxygen restriction in skeletal muscle from rodents and humans

In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile \uce\ub1 subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O2 delivery by tuning its metabolism. The present study provides a comprehensive overview of skeletal muscle metabolic adaptation to hypoxia in mice and in human subjects exposed for 7/9 and 19 days to high altitude levels. The investigation was carried out combining proteomics, qRT-PCR mRNA transcripts analysis, and enzyme activities assessment in rodents, and protein detection by antigen antibody reactions in humans and rodents. Results indicate that the skeletal muscle react to a decreased O2 delivery by rewiring the TCA cycle. The first TCA rewiring occurs in mice in 2-day hypoxia and is mediated by cytosolic malate whereas in 10-day hypoxia the rewiring is mediated by Idh1 and Fasn, supported by glutamine and HIF-2\uce\ub1 increments. The combination of these specific anaplerotic steps can support energy demand despite HIFs degradation. These results were confirmed in human subjects, demonstrating that the TCA double rewiring represents an essential factor for the maintenance of muscle homeostasis during adaptation to hypoxia

Sodium bicarbonate supplementation improves severe-intensity intermittent exercise under moderate acute hypoxic conditions

Acute moderate hypoxic exposure can substantially impair exercise performance, which occurs with a concurrent exacerbated rise in hydrogen cation (H+) production. The purpose of this study was therefore, to alleviate this acidic stress through sodium bicarbonate (NaHCO3) supplementation and determine the corresponding effects on severe intensity intermittent exercise performance. Eleven recreationally active individuals participated in this randomised, double-blind, crossover study performed under acute normobaric hypoxic conditions (FiO2% = 14.5%). Pre-experimental trials involved the determination of time to attain peak bicarbonate anion concentrations ([HCO3-]) following NaHCO3 ingestion. The intermittent exercise tests involved repeated 60 s work in their severe intensity domain and 30 s recovery at 20 W to exhaustion. Participants ingested either 0.3 g·kg bm-1 of NaHCO3 or a matched placebo of 0.21 g·kg bm-1 of sodium chloride prior to exercise. Exercise tolerance (+110.9 ± 100.6 s; 95% CI: 43.3 to 178 s; g = 1.0) and work performed in the severe intensity domain (+5.8 ± 6.6 kJ; 95% CI: 1.3 to 9.9 kJ; g = 0.8) were enhanced with NaHCO3 supplementation. Furthermore, a larger post-exercise blood lactate concentration was reported in the experimental group (+4 ± 2.4 mmol·l-1; 95% CI: 2.2 to 5.9; g = 1.8), while blood [HCO3-] and pH remained elevated in the NaHCO3 condition throughout experimentation. In conclusion, this study reported a positive effect of NaHCO3 under acute moderate hypoxic conditions during intermittent exercise and therefore, may offer an ergogenic strategy to mitigate hypoxic induced declines in exercise performance