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

Oxygen affinity of blood in altitude Sherpas

Oxygen equilibrium curves on blood within 6 h from sampling have been estimated from polarographic measurements of oxyhemoglobin concentration, in 13 male 14- to 50-yr old Sherpas residing at 3,850 m above sea level (Kumjung, Nepal). In samples with red blood cell counts = 4.7 +/- 0.8 (SD) x 10(6)/mm3, total hemoglobin concentration [Hb] = 17.0 +/- 1.9 g/dl, and hematocrit = 53.3 +/- 5.0, the mean oxygen half-saturation of hemoglobin (P50) (pH = 7.4 and PCO2 = 40 Torr) was 27.3 +/- 1.8 Torr. The P50 of altitude Sherpas was not significantly different from that of acclimatized lowlanders (28.2 +/- 1.3; n = 7), sea-level Caucasian residents (26.5 +/- 1.0; n = 17), and Sherpas at sea level (27.1; n = 3). The 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio ([2,3-DPG]/[Hb]) in altitude Sherpas was 1.22 +/- 0.03, the same as that of acclimatized Caucasians (1.22 +/- 0.10). The Bohr effect measured for the blood of one altitude Sherpas by the ratio deltalog P50/deltapH was -0.32 and -0.45 at PCO2 levels of 40 and 20 Torr, respectively. These values are not significantly different from those found in Caucasians at sea level where deltalog P50/deltalpH was -0.35 and -0.42, respectively. It is concluded that the P50 in native highlanders is not significantly different from that observed in sea-level dwellers. [2,3-DPG]/[Hb] at altitude, both in natives and in newcomers, is 20% higher than in sea-level residents

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

HUMAN RED-BLOOD-CELL AGING AT 5,050-M ALTITUDE - A ROLE DURING ADAPTATION TO HYPOXIA

To test the hypothesis that the human red blood cell aging process participates actively in the adaptation to hypoxia, we studied some physical and biochemical hematologic variables in 10 volunteers at sea level (SL) and after 1 (1WK) or 5 wk (5WK) of exposure to 5,050-m altitude. The 2,3- diphosphoglycerate-to-hemoglobin ratio (2,3-DPG/Hb) was 0.88 \ub1 0.03 (mol/mol) at SL and increased to 1.08 \ub1 0.03 (P = 0.002) and 1.28 \ub1 0.05 (P < 0.0001) at 1WK and 5WK, respectively. The average red blood cell density (D50), which is inversely proportional to the fraction of young red blood cells and is therefore an index of the red blood cell aging process, was 1.1053 \ub1 0.0007 g/ml at SL and decreased to 1.1046 \ub1 0.0008 g/ml (NS) and 1.1018 \ub1 0.0008 g/ml (P < 0.0001) at 1WK and 5WK, respectively. D50 was correlated with 2,3-DPG/Hb at SL (P = 0.004), only weakly at 5WK (P = 0.1), but not at all at 1WK. The arterial O2 saturation was correlated with the change of 2,3-DPG/Hb in 1WK (P = 0.02) and that of D50 in 5WK (P = 0.04). It is concluded that short-term (1WK) increase of 2,3-DPG/Hb is not associated with the erythropoietic response but is presumably due to respiratory alkalosis. By contrast, after prolonged hypoxia (5WK), erythropoiesis may provide an efficient way for increasing blood 2,3-DPG through an augmented proportion of young red blood cells

Blood O2 affinity and maximal O2 consumption in elite bicycle racers

The PO2 at which hemoglobin is half-saturated with O2 (P50) at 37\ub0C, PCO2 = 42 Torr, measured pH and 2,3-diphosphoglycerate-to-hemoglobin concentration ratio ([2,3-DPG]/[Hb]) values, Hill's coefficient (n) at rest, and maximal O2 consumption (V\u307O2(max)) were determined in 11 world-class professional bicycle racers off-season (control, C), after 3 mo of 3 h daily training (preseason, PrS), and after additional 6 mo of competitions (competitive season, CoS). The results indicate that the P50 observed in trained athletes was the same as that of a comparable group of sedentary subjects (Sed) under the same conditions of pH, PCO2, and [2,3-DPG]/[Hb] and was similar to that obtained after 'normalization' in respect to pH and the [2,3-DPG]/[Hb]; [2,3-DPG]/[Hb] increased as a function of training from 0.72 to 0.95 (P < 0.001); the slope of the central portion of the O2 equilibrium curve (OEC) was nearly unaffected by endurance training as indicated by the n value (n(CoS) = 2.70 \ub1 0.08; n(Sed) = 2.65 \ub1 0.08); and V\u307O2(max) increased in the course of training 7 and 9% (P < 0.001), respectively, when expressed in absolute units or per kilogram body weight. The V\u307O2(max) predicted on the basis of a computer simulation does not increase significantly as a consequence of the measured rise in [2,3-DPG]. Therefore, the observed increase of V\u307O2(max) cannot be explained with adaptive changes of the OEC. The present results differ from previous findings reported in other types of athletes

Muscle Oxygen Delivery in the Forearm and in the Vastus Lateralis Muscles in Response to Resistance Exercise: A Comparison Between Nepalese Porters and Italian Trekkers

Altitude ascending represents an intriguing experimental model reproducing physiological and pathophysiological conditions sharing hypoxemia as the denominator. The aim of the present study was to investigate fractional oxygen extraction and blood dynamics in response to hypobaric hypoxia and to acute resistance exercises, taking into account several factors including different ethnic origin and muscle groups. As part of the “Kanchenjunga Exploration &amp; Physiology” project, six Italian trekkers and six Nepalese porters took part in a high altitude trek in the Himalayas. The measurements were carried out at low (1,450 m) and high altitude (HA; 4,780 m). Near-infrared spectroscopy (NIRS)-derived parameters, i.e., Tot-Hb and tissue saturation index (TSI), were gathered at rest and after bouts of 3-min resistive exercise, both in the quadriceps and in the forearm muscles. TSI decreased with altitude, particularly in forearm muscles (from 66.9 to 57.3%), whereas the decrement was less in the quadriceps (from 62.5 to 57.2%); Nepalese porters were characterized by greater values in thigh TSI than Italian trekkers. Tot-Hb was increased after exercise. At altitude, such increase appeared to be higher in the quadriceps. This effect might be a consequence of the long-term adaptive memory due to the frequent exposures to altitude. Although speculative, we suggest a long-term adaptation of the Nepalese porters due to improved oxygenation of muscles frequently undergoing hypoxic exercise. Muscle structure, individual factors, and altitude exposure time should be taken into account to move on the knowledge of oxygen delivery and utilization at altitude

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