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

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

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

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

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

Isometric thermogenesis at rest and during movement: a neglected variable in energy expenditure and obesity predisposition

Isometric thermogenesis as applied to human energy expenditure refers to heat production resulting from increased muscle tension. While most physical activities consist of both dynamic and static (isometric) muscle actions, the isometric component is very often essential for the optimal performance of dynamic work given its role in coordinating posture during standing, walking and most physical activities of everyday life. Over the past 75 years, there has been sporadic interest into the relevance of isometric work to thermoregulatory thermogenesis and to adaptive thermogenesis pertaining to body-weight regulation. This has been in relation to (i) a role for skeletal muscle minor tremor or microvibration – nowadays referred to as ‘resting muscle mechanical activity’ – in maintaining body temperature in response to mild cooling; (ii) a role for slowed skeletal muscle isometric contraction–relaxation cycle as a mechanism for energy conservation in response to caloric restriction and weight loss and (iii) a role for spontaneous physical activity (which is contributed importantly by isometric work for posture maintenance and fidgeting behaviours) in adaptive thermogenesis pertaining to weight regulation. This paper reviews the evidence underlying these proposed roles for isometric work in adaptive thermogenesis and highlights the contention that variability in this neglected component of energy expenditure could contribute to human predisposition to obesity

Ethanol-induced formation of colorectal tumours and precursors in a mouse model of Lynch syndrome

Lynch Syndrome (LS) confers an inherited cancer predisposition, particularly for colorectal cancer, due to germline mutations in one of the DNA mismatch repair (MMR) genes, such as MSH2. MMR is a DNA damage repair pathway involved in the removal of base mismatches and insertion/deletion loops, caused by several endogenous and exogenous factors. Loss of MMR through somatic alteration of the wild-type MMR allele in LS results in defective MMR (dMMR). Lifestyle factors can modify cancer risk for LS and sporadic patients. Ethanol and its metabolite acetaldehyde, are classified as group one carcinogens by the International Agency for Research on Cancer, and are risk factors for sporadic cancers of the upper aerodigestive tract, liver, breast and colorectum. Acetaldehyde is metabolised to acetate by the Aldh family of enzymes, particularly Aldh1b1 in the intestines. Acetaldehyde is very reactive and may cause a range of DNA lesions. However, DNA repair pathways responsible for correcting such lesions remain unknown. It was hypothesized that MMR plays a role in protecting intestinal cells from ethanol/acetaldehyde-induced DNA damage. This study aimed to determine if there is a gene/environment interaction between dMMR and ethanol/acetaldehyde that accelerates colorectal tumour development and progression.A conditional Msh2 knockout (“Msh2-LS”) mouse model with one deleted and one conditional knockout Msh2 allele was used, as it mimics the LS patients’ pattern of MMR gene inactivation. The Msh2-LS model mice were fed either with 20% ethanol in drinking water or normal drinking water. Long-term ethanol consumption led to large intestinal mucosal epithelial hyperproliferation and adenoma formation in 65% (15/23) mice and, in some cases, invasive adenocarcinoma (5/23 mice, 21.7%) within 6 months (mostly in the proximal and mid-colon), compared with 0% (0/23 mice) at 6 months and only one colonic tumour after 15 months in the water-treated mice (p<0.0001). No small intestinal tumours were observed. Additionally, a conditional Aldh1b1 knockout (Aldh1b1flox/flox) Msh2-LS mouse model and a constitutive Aldh1b1 knockout (Aldh1b1-/-) Msh2-LS mouse model were generated, in which the lack of Aldh1b1 enzyme caused increased acetaldehyde levels and acetaldehyde-induced DNA damage. In these Aldh1b1-deficient mice, long-term ethanol consumption led to increased numbers of colorectal adenomas per mouse (4.2, 21 neoplasms in 5 tumour-bearing conditional Aldh1b1fl/fl Msh2-LS mice; and 4.8, 35 neoplasms in 8 tumour-bearing constitutive Aldh1b1-/- Msh2-LS mice) compared with 2.4 (36 neoplasms in 15 tumour-bearing mice) colorectal adenomas per mouse observed in the Msh2-LS mouse model with wild-type Aldh1b1 (p=0.0319 and p=0.0103) , but no colonic tumours were observed in water-treated controls.Precursor lesions were observed as dMMR crypts in the murine colon in all of these mouse models, and their quantification showed increased numbers of dMMR crypt foci in ethanol-treated mice compared with water-treated controls (p=0.0029 in Aldh1b1wt Msh2-LS mice, p=0.0006 in Aldh1b1fl/fl Msh2-LS mice and p<0.0001 in Aldh1b1-/- Msh2-LS mice). A significant increase in DNA damage was detected in the large intestinal epithelium of ethanol-treated mice of all genotypes compared with the respective water-treated controls (p=0.0009 in Aldh1b1wt Msh2-LS mice, p<0.0001 in Aldh1b1fl/fl Msh2-LS mice and in Aldh1b1-/- Msh2-LS mice), along with increased plasma acetaldehyde levels in ethanol-treated mice and acetaldehyde levels were higher in the plasma of Aldh1b1flox/flox Msh2-LS mice and Aldh1b1-/- Msh2-LS mice than in the plasma of Msh2-LS mice.In this study, evidence was provided for a role for Msh2 in protecting the MMR-proficient colonic epithelial cells against ethanol/acetaldehyde-induced DNA damage by activating DNA mismatch repair, triggering cell cycle arrest or cell death by apoptosis. A key role for Aldh1b1 was confirmed for protecting the large intestines from acetaldehyde-induced DNA damage and tumour formation. Long-term ethanol/acetaldehyde exposure was shown to accelerate dMMR-driven intestinal tumour formation and this is proposed to act via promoting proliferation (mucosal epithelial hyperproliferation) and suppressing apoptosis, thus enhancing survival of aberrant dMMR intestinal epithelial cells/crypts relative to MMR-proficient intestinal epithelial cells/crypts, leading to adenoma development (with microsatellite instability) with some progressing to adenocarcinomas. In conclusion, there is strong evidence for a gene/environment interaction between acetaldehyde/dMMR, causing the acceleration of dMMR-driven intestinal tumour formation upon ethanol exposure

The role of ecosystem services in the spatial assessment of land degradation: a transdisciplinary study in the Ethiopian Great Rift Valley

Land degradation is a widespread problem that affects about 1.5 billion people globally. It can be defined as the decline in the productive capacity of the land, and the loss of functionality of ecosystems. Overall, land degradation leads to ecosystem services degradation, because it affects and causes the depletion of several soil functions (e.g. sediment retention, nutrient cycling, carbon stocks, and water retention). Therefore, it is also a constraint in securing food production and it could cause food insecurity. Hence, land degradation represents a considerable problem especially in developing countries, where people strongly rely on the ecosystems and natural resources for their livelihoods. The principal aim of this study was to assess land degradation by integrating different sources of knowledges and data, to derive a synthesis relevant to inform decision-making processes, and to target priority areas for conservation and restoration interventions. In this study, three ecosystem services (ESS) were modelled to infer land degradation in a small area, in the Halaba special woreda, located in the Ethiopian Great Rift Valley. In particular, sediment erosion and retention, nutrient retention and export, and carbon storage and sequestration were modelled. Data from a local soil survey, from global coverage datasets, and from a supervised land use cover classification were used for the ESS modelling. Remote Sensing data were used during the parametrisation phase of the ESS modelling. Local knowledges and perspectives were gathered using an extensive participatory approach that targeted the communities of three kebeles in the study area, and the experts of the Halaba woreda Agricultural Office. 33 focus group discussions and 32 semi-structured interviews were conducted in the summer 2016. The information acquired through the ESS modelling and during the participatory approach was then integrated in a Bayesian Belief Network (BBN), a probabilistic graphical model, to derive a spatial explicit land degradation risk assessment. The results showed that assessing land degradation through the lens of key ecosystem services represents a valid approach. The ESS modelling results showed that the study area is characterised by high soil erosion rates, low carbon storage and sequestration, and low nitrogen retention. Moreover, the ESS modelling also showed that using data from global coverage datasets could affect the reliability of the ESS assessment. Furthermore, the qualitative study, derived from the participatory approach, highlighted the presence of complex linkages between environmental and socio-economic factors, which exacerbate land degradation. The integration of ESS modelling results, participatory approach and literature data in the BBN proved to be an efficient approach to derive a synthesis of the several knowledges acquired during the several steps of this PhD project. Overall, this study demonstrated that a transdisciplinary and interdisciplinary approach is an effective means to address land degradation risks, taking into consideration people needs and priorities. In order to reverse land degradation trends, there is the need to adopt intense restoration and sustainable land management programs. However, there is also the need to couple conservation interventions with development strategies, such as market access and development, land tenure system improvements, off-farm job opportunities generation, and livelihoods diversification. This could foster land conservation and restoration, and could support sustainable economic growth and inclusive development

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

Pulmonary oxygen uptake and muscle deoxygenation kinetics during recovery in trained and untrained male adolescents

Previous studies have demonstrated faster pulmonary oxygen uptake ( V ˙ O 2 ) kinetics in the trained state during the transition to and from moderate-intensity exercise in adults. Whilst a similar effect of training status has previously been observed during the on-transition in adolescents, whether this is also observed during recovery from exercise is presently unknown. The aim of the present study was therefore to examine V ˙ O 2 kinetics in trained and untrained male adolescents during recovery from moderate-intensity exercise. 15 trained (15 ± 0.8 years, V ˙ O 2max 54.9 ± 6.4 mL kg−1 min−1) and 8 untrained (15 ± 0.5 years, V ˙ O 2max 44.0 ± 4.6 mL kg−1 min−1) male adolescents performed two 6-min exercise off-transitions to 10 W from a preceding “baseline” of exercise at a workload equivalent to 80% lactate threshold; V ˙ O 2 (breath-by-breath) and muscle deoxyhaemoglobin (near-infrared spectroscopy) were measured continuously. The time constant of the fundamental phase of V ˙ O 2 off-kinetics was not different between trained and untrained (trained 27.8 ± 5.9 s vs. untrained 28.9 ± 7.6 s, P = 0.71). However, the time constant (trained 17.0 ± 7.5 s vs. untrained 32 ± 11 s, P < 0.01) and mean response time (trained 24.2 ± 9.2 s vs. untrained 34 ± 13 s, P = 0.05) of muscle deoxyhaemoglobin off-kinetics was faster in the trained subjects compared to the untrained subjects. V ˙ O 2 kinetics was unaffected by training status; the faster muscle deoxyhaemoglobin kinetics in the trained subjects thus indicates slower blood flow kinetics during recovery from exercise compared to the untrained subjects