Biomedical subjects

Tom D Brutsaert

Publications and source records attributed to Tom D Brutsaert.

12 recordsLinked to original sources

PubMed2026

High-altitude hypoxia alters the visual control of standing balance in lowlanders and Tibetan highlanders.

High-altitude hypoxia affects both visual function and postural control, yet the influence of optic-flow perturbations on standing balance under hypoxic stress remains unclear. Tibetan highlanders (TH) exhibit adaptations to chronic hypoxia, but whether their visually driven postural responses differ from those of lowlanders (LL) has not been investigated. We examined how high-altitude exposure and acclimatization influence static and dynamic visual contributions to balance by delivering sinusoidal optic-flow perturbations in virtual reality at low altitude (1,400 m) and after incremental ascent to high altitude (4,300 m) in acclimatizing LL (n = 15) and TH (n = 14). Anteroposterior center of pressure (AP CoP) velocity and mean power frequency (MPF) were measured during three visual-field conditions (full-, central-, and peripheral-vision) and two optic-flow velocities (peak 1 m/s and 8 m/s at 0.25 Hz). At high altitude, both groups showed attenuated responses to optic flow compared with 1,400 m, reflected by reduced AP CoP velocity and lower MPF across visual-field conditions, consistent with reduced responsiveness to dynamic visual-motion cues under high altitude hypoxia. In contrast, during eyes-open quiet stance [no virtual reality (VR)], TH but not LL exhibited increased AP CoP velocity and MPF at 4,300 m, and no altitude effect was observed with eyes-closed in either group. This finding indicates that TH adopt a visually dependent postural strategy at altitude, whereas LL show minimal changes in static visual balance control but reduced responsiveness to fast dynamic motion. Together, these findings demonstrate that high-altitude hypoxia disrupts dynamic visual processing for balance control in both groups, while revealing group differences in the use of static visual cues during quiet stance.NEW & NOTEWORTHY This is the first study to investigate how high-altitude hypoxia alters visually driven postural control using virtual reality (VR) optic-flow perturbations. We show that hypoxia attenuates sway responses to optic-flow in both lowlanders and Tibetan highlanders, and that visual weighting differs between these groups. These findings reveal altitude- and population-related changes in sensory weighting during standing balance, advancing sensorimotor understanding of postural control in hypoxia.

Humans↗

PubMed2006

What makes a champion? Explaining variation in human athletic performance.

Variation in human athletic performance is determined by a complex interaction of socio-cultural, psychological, and proximate physiological factors. Human physiological trait variance has both an environmental and genetic basis, although the classic gene-environment dichotomy is clearly too simplistic to understand the full range of variation for most proximate determinants of athletic performance, e.g., body composition. In other words, gene and environment interact, not just over the short term, but also over the lifetime of an individual with permanent effects on the adult phenotype. To further complicate matters, gene and environment may also be correlated. That is, genetically gifted individuals may be identified as children and begin training pulmonary, cardiovascular, and muscle systems at an early critical age. This review covers evidence in support of a genetic basis to human athletic performance, with some emphasis on the recent explosion of candidate gene studies. In addition, the review covers environmental influences on athletic performance with an emphasis on irreversible environmental effects, i.e., developmental effects that may accrue during critical periods of development either before conception (epigenetic effects), during fetal life (fetal programming), or during childhood and adolescence. Throughout, we emphasize the importance of gene-environment interaction (G x E) as a means of understanding variation in human physiological performance and we promote studies that integrate genomics with developmental biology.

Cardiovascular Physiological Phenomena↗

PubMed2006

Finding the genes underlying adaptation to hypoxia using genomic scans for genetic adaptation and admixture mapping.

The complete sequencing the human genome and recent analytical advances have provided the opportunity to perform genome-wide studies of human variation. There is substantial potential for such population-genomic approaches to assist efforts to uncover the historical and demographic histories of human populations. Additionally, these genome-wide datasets allow for investigations of variability among genomic regions. Although all genomic regions in a population have experienced the same demographic events, they have not been affected by these events in precisely the same way. Much of the variability among genomic regions is simply the result of genetic drift (i.e., gene frequency changes resulting from the effects of small breeding-population size), but some is also the result of genetic adaptation, which will only affect the gene under selection and nearby regions. We have used a new DNA typing assay that allows for the genotyping of thousands of SNPs on hundreds of samples to identify regions most likely to have been affected by genetic adaptation. Populations that have inhabited different niches (e.g., high-altitude regions) can be used to identify genes underlying the physiological differences. We have used two methods (admixture mapping and genome scans for genetic adaptation) founded on the population-genomic paradigms to search for genes underlying population differences in response to chronic hypoxia. There is great promise that together these methods will facilitate the discovery of genes influencing hypoxic response.

Alleles↗

PubMed2005

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Adult↗

PubMed2005

Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation.

Understanding the distribution of human genetic variation is an important foundation for research into the genetics of common diseases. Some of the alleles that modify common disease risk are themselves likely to be common and, thus, amenable to identification using gene-association methods. A problem with this approach is that the large sample sizes required for sufficient statistical power to detect alleles with moderate effect make gene-association studies susceptible to false-positive findings as the result of population stratification. Such type I errors can be eliminated by using either family-based association tests or methods that sufficiently adjust for population stratification. These methods require the availability of genetic markers that can detect and, thus, control for sources of genetic stratification among populations. In an effort to investigate population stratification and identify appropriate marker panels, we have analysed 11,555 single nucleotide polymorphisms in 203 individuals from 12 diverse human populations. Individuals in each population cluster to the exclusion of individuals from other populations using two clustering methods. Higher-order branching and clustering of the populations are consistent with the geographic origins of populations and with previously published genetic analyses. These data provide a valuable resource for the definition of marker panels to detect and control for population stratification in population-based gene identification studies. Using three US resident populations (European-American, African-American and Puerto Rican), we demonstrate how such studies can proceed, quantifying proportional ancestry levels and detecting significant admixture structure in each of these populations.

Chromosomes, Human, X↗

PubMed2004

HIF and VEGF relationships in response to hypoxia and sciatic nerve stimulation in rat gastrocnemius.

To determine if hypoxia-inducible factor-1 (HIF-1) may regulate skeletal muscle vascular endothelial growth factor (VEGF) expression in response to exercise or hypoxia, rats underwent 1h sciatic nerve electrical stimulation (ES), hypoxic exposure (H) or combined stimuli. HIF-1alpha protein levels increased six-fold with maximal (8V) ES with or without H. Similar HIF-1alpha increases occurred with sub-maximal (6V and 4V) ES plus H, but not in sub-maximal ES or H alone. VEGF mRNA and protein levels increased three-fold in sub-maximal ES or H alone, six-fold in sub-maximal ES plus H, 6.3-fold with maximal ES, and 6.5-fold after maximal ES plus H. These data suggest: (1) intracellular hypoxia during normoxic exercise may exceed that during 8% oxygen breathing at rest and is more effective in stimulating HIF-1alpha; (2) HIF-1 may be an important regulator of exercise-induced VEGF transcription; and (3) breathing 8% O(2) does not alter HIF-1alpha expression in skeletal muscle, implying that exercise-generated signals contribute to the regulation of HIF-1alpha and/or VEGF.

Animals↗

PubMed2004

Effects of birthplace and individual genetic admixture on lung volume and exercise phenotypes of Peruvian Quechua.

Forced vital capacity (FVC) and maximal exercise response were measured in two populations of Peruvian males (age, 18-35 years) at 4,338 m who differed by the environment in which they were born and raised, i.e., high altitude (Cerro de Pasco, Peru, BHA, n = 39) and sea level (Lima, Peru, BSL, n = 32). BSL subjects were transported from sea level to 4,338 m, and were evaluated within 24 hr of exposure to hypobaric hypoxia. Individual admixture level (ADMIX, % Spanish ancestry) was estimated for each subject, using 22 ancestry-informative genetic markers and also by skin reflectance measurement (MEL). Birthplace accounted for the approximately 10% larger FVC (P < 0.001), approximately 15% higher maximal oxygen consumption (VO(2)max, ml.min(-1).kg(-1)) (P < 0.001), and approximately 5% higher arterial oxygen saturation during exercise (SpO(2)) (P < 0.001) of BHA subjects. ADMIX was low in both study groups, averaging 9.5 +/- 2.6% and 2.1 +/- 0.3% in BSL and BHA subjects, respectively. Mean underarm MEL was significantly higher in the BSL group (P < 0.001), despite higher ADMIX. ADMIX was not associated with any study phenotype, but study power was not sufficient to evaluate hypotheses of genetic adaptation via the ADMIX variable. MEL and FVC were positively correlated in the BHA (P = 0.035) but not BSL (P = 0.335) subjects. However, MEL and ADMIX were not correlated across the entire study sample (P = 0.282). In summary, results from this study emphasize the importance of developmental adaptation to high altitude. While the MEL-FVC correlation may reflect genetic adaptation to high altitude, study results suggest that alternate (environmental) explanations be considered.

Acclimatization↗

PubMed2004

Absence of work efficiency differences during cycle ergometry exercise in Bolivian Aymara.

This study tested the hypothesis that Andean natives are adapted to high altitude (HA) via high work efficiency during exercise in hypoxia. A total of 186 young males and females were tested in Bolivia, comprising eight different subject groups. Groups were identified based on gender, ancestry (Aymara vs. European), altitude of birth (highlands vs. lowlands), and the altitude where tested (420, 3600, 3850 m). This design allows partitioning of ancestral (i.e., genetic) and developmental effects. To minimize measurement error, subjects were given two submaximal exercise tests on a cycle ergometer (on separate days). Each test consisted of four 5-min work bouts (levels), each separated by a 5-min rest period. For all groups, the oxygen consumption (V(O2))-work rate relationship was not different from the sea-level reference. Gross and net efficiencies (GE and NE) were not different between groups at any work level, with the exception of European men born in the lowlands and acclimatized and tested at 3600 m. These men showed slightly lower V(O2) at high work output, but this may be due to a nonsteady-state V(O2) kinetic, rather than to an altered steady-state V(O2)-work rate relationship per se. There were no significant group differences in delta efficiency (DE). In sum, these results provide no support for the hypothesis of energetic advantage during submaximal work in Andean HA natives. A review and analysis of the literature suggest that the same is true for HA natives in the Himalayas.

Acclimatization↗

PubMed2003

Spanish genetic admixture is associated with larger V(O2) max decrement from sea level to 4338 m in Peruvian Quechua.

Quechua in the Andes may be genetically adapted to altitude and able to resist decrements in maximal O2 consumption in hypoxia (DeltaVo2 max). This hypothesis was tested via repeated measures of Vo2 max (sea level vs. 4338 m) in 30 men of mixed Spanish and Quechua origins. Individual genetic admixture level (%Spanish ancestry) was estimated by using ancestry-informative DNA markers. Genetic admixture explained a significant proportion of the variability in DeltaVo2 max after control for covariate effects, including sea level Vo2 max and the decrement in arterial O2 saturation measured at Vo2 max (DeltaSpO2 max) (R2 for admixture and covariate effects approximately 0.80). The genetic effect reflected a main effect of admixture on DeltaVo2 max (P = 0.041) and an interaction between admixture and DeltaSpO2 max (P = 0.018). Admixture predicted DeltaVo2 max only in subjects with a large DeltaSpO2 max (P = 0.031). In such subjects, DeltaVo2 max was 12-18% larger in a subgroup of subjects with high vs. low Spanish ancestry, with least squares mean values (+/-SE) of 739 +/- 71 vs. 606 +/- 68 ml/min, respectively. A trend for interaction (P = 0.095) was also noted between admixture and the decrease in ventilatory threshold at 4338 m. As previously, admixture predicted DeltaVo2 max only in subjects with a large decrease in ventilatory threshold. These findings suggest that the genetic effect on DeltaVo2 max depends on a subject's aerobic fitness. Genetic effects may be more important (or easier to detect) in athletic subjects who are more likely to show gas-exchange impairment during exercise. The results of this study are consistent with the evolutionary hypothesis and point to a better gas-exchange system in Quechua.

Adult↗

PubMed2003

Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women.

BACKGROUND: Tissue iron depletion may negatively affect endurance performance and muscle fatigability. OBJECTIVE: We investigated tissue-level iron depletion and progressive fatigue of the quadriceps during dynamic knee-extension exercise in young women. DESIGN: Twenty iron-depleted (serum ferritin < 20 micro g/L), nonanemic (hemoglobin > 110 g/L) women (macro x +/- SEM age: 29.1 +/- 1.2 y) received iron (iron group) or placebo (placebo group) for 6 wk in a randomized, double-blind trial (n = 10 per group). A protocol integrating 2-3-s maximal voluntary static contractions (MVCs) with dynamic knee extensions was used to assess fatigue. RESULTS: No significant differences between the groups in baseline iron status, MVC at rest, or MVC at the end of the protocol were observed. After treatment, serum iron and transferrin saturation increased significantly in the iron group (P = 0.02 and P = 0.03, respectively). Serum transferrin receptor concentrations increased significantly in the placebo group (P < 0.01) but not in the iron group. After treatment, the rate of decrease in MVC was attenuated in the iron group but not in the placebo group (P = 0.01). In the iron group, MVC at the sixth minute of the fatigue protocol and MVC at the end of the protocol were approximately 15% (P = 0.04) and approximately 27% higher (P < 0.01), respectively, after treatment. These improvements were not related to changes in iron-status indexes or tissue iron stores, although power was low (< 0.50) to detect these relations. CONCLUSIONS: Iron supplementation was associated with a significant improvement in muscle fatigability. Interpretation regarding the direct role of tissue iron status is limited by the study's low power to detect relations between tissue iron improvement and decreased muscle fatigue.

Adolescent↗

PubMed2002

Regional differences in expression of VEGF mRNA in rat gastrocnemius following 1 hr exercise or electrical stimulation.

BACKGROUND: Vascular endothelial growth factor (VEGF) mRNA levels increase in rat skeletal muscle after a single bout of acute exercise. We assessed regional differences in VEGF165 mRNA levels in rat gastrocnemius muscle using in situ hybridization after inducing upregulation of VEGF by treadmill running (1 hr) or electrical stimulation (1 hr). Muscle functional regions were defined as oxidative (primarily oxidative fibers, I and IIa), or glycolytic (entirely IIb or IId/x fibers). Functional regions were visualized on muscle cross sections that were matched in series to slides processed through in situ hybridization with a VEGF165 probe. A greater upregulation in oxidative regions was hypothesized. RESULTS: Total muscle VEGF mRNA (via Northern blot) was upregulated 3.5-fold with both exercise and with electrical stimulation (P = 0.015). Quantitative densitometry of the VEGF mRNA signal via in situ hybridization reveals significant regional differences (P <or= 0.01) and protocol differences (treadmill, electrical stimulation, and control, P <or= 0.05). Mean VEGF mRNA signal was higher in the oxidative region in both treadmill run (approximately 7%, N = 4 muscles, P <or= 0.05) and electrically stimulated muscles (approximately 60%, N = 4, P <or= 0.05). These regional differences were not significantly different from control muscle (non-exercised, non-stimulated, N = 2 muscles), although nearly so for electrically stimulated muscle (P = 0.056). CONCLUSIONS: Moderately higher VEGF mRNA signal in oxidative muscle regions is consistent with regional differences in capillary density. However, it is not possible to determine if the VEGF mRNA signal difference is important in either the maintenance of regional capillarity differences or exercise induced angiogenesis.

Animals↗

PubMed2002

Effect of menstrual cycle phase on exercise performance of high-altitude native women at 3600 m.

At sea level normally menstruating women show increased ventilation (VE) and hemodynamic changes due to increased progesterone (P) and estrogen (E2) levels during the mid-luteal (L) compared to the mid-follicular (F) phase of the ovarian cycle. Such changes may affect maximal exercise performance. This repeated-measures, randomized study, conducted at 3600 m, tests the hypothesis that a P-mediated increase in VE increases maximal oxygen consumption (V(O(2)max)) during the L phase relative to the F phase in Bolivian women, either born and raised at high altitude (HA), or resident at HA since early childhood. Subjects (N=30) enrolled in the study were aged 27.7 +/- 0.7 years (mean +/- S.E.M.) and non-pregnant, non-lactating, relatively sedentary residents of La Paz, Bolivia, who were not using hormonal contraceptives. Mean salivary P levels at the time of the exercise tests were 63.3 pg ml(-1) and 22.9 pg ml(-1) for the L and F phases, respectively. Subset analyses of submaximal (N=23) and maximal (N=13) exercise responses were conducted only with women showing increased P levels from F to L and, in the latter case, with those also achieving true (V(O(2)max)). Submaximal exercise VE and ventilatory equivalents were higher in the L phase (P<0.001). P levels were significantly correlated to the submaximal exercise VE (r=0.487, P=0.006). Maximal work output (W) was higher (approximately 5 %) during the L phase (P=0.044), but (V(O(2)max)) (l min(-1)) was unchanged (P=0.063). Post-hoc analyses revealed no significant relationship between changes in P levels and changes in (V(O(2)max))) from F to L (P=0.072). In sum, the menstrual cycle phase has relatively modest effects on ventilation, but no effect on (V(O(2)max)) of HA native women.

Adult↗