Diving response and arterial oxygen saturation during apnea and exercise in breath-hold divers.

This study addressed the effects of apnea in air and apnea with face immersion in cold water (10 degrees C) on the diving response and arterial oxygen saturation during dynamic exercise. Eight trained breath-hold divers performed steady-state exercise on a cycle ergometer at 100 W. During exercise, each subject performed 30-s apneas in air and 30-s apneas with face immersion. The heart rate and arterial oxygen saturation decreased and blood pressure increased during the apneas. Compared with apneas in air, apneas with face immersion augmented the heart rate reduction from 21 to 33% (P < 0.001) and the blood pressure increase from 34 to 42% (P < 0.05). The reduction in arterial oxygen saturation from eupneic control was 6.8% during apneas in air and 5.2% during apneas with face immersion (P < 0.05). The results indicate that augmentation of the diving response slows down the depletion of the lung oxygen store, possibly associated with a larger reduction in peripheral venous oxygen stores and increased anaerobiosis. This mechanism delays the fall in alveolar and arterial PO(2) and, thereby, the development of hypoxia in vital organs. Accordingly, we conclude that the human diving response has an oxygen-conserving effect during exercise.     

Knee angle-dependent oxygen consumption during isometric contractions of the knee extensors determined with near-infrared spectroscopy.

Fatigue resistance of knee extensor muscles is higher during voluntary isometric contractions at short compared with longer muscle lengths. In the present study we hypothesized that this would be due to lower energy consumption at short muscle lengths. Ten healthy male subjects performed isometric contractions with the knee extensor muscles at a 30, 60, and 90 degrees knee angle (full extension = 0 degrees ). At each angle, muscle oxygen consumption (m.VO2) of the rectus femoris, vastus lateralis, and vastus medialis muscle was obtained with near-infrared spectroscopy. m.VO2 was measured during maximal isometric contractions and during contractions at 10, 30, and 50% of maximal torque capacity. During all contractions, blood flow to the muscle was occluded with a pressure cuff (450 mmHg). m.VO2 significantly (P < 0.05) increased with torque and at all torque levels, and for each of the three muscles. m.VO2 was significantly lower at 30 degrees compared with 60 degrees and 90 degrees and m.VO2 was similar (P > 0.05) at 60 degrees and 90 degrees . Across all torque levels, average (+/- SD) m.VO2 at the 30 degrees angle for vastus medialis, rectus femoris, and vastus lateralis, respectively, was 70.0 +/- 10.4, 72.2 +/- 12.7, and 75.9 +/- 8.0% of the average m.VO2 obtained for each torque at 60 and 90 degrees . In conclusion, oxygen consumption of the knee extensors was significantly lower during isometric contractions at the 30 degrees than at the 60 degrees and 90 degrees knee angle, which probably contributes to the previously reported longer duration of sustained isometric contractions at relatively short muscle lengths.     

Development of a new instrument to measure oxygen saturation and total hemoglobin volume in local skin by near-infrared spectroscopy and its clinical application

The oxygen saturation (StO₂) and total hemoglobin volume in cutaneous blood are closely related to cutaneous metabolism and are important factors in determining the skin color. Most conventional apparatuses for the measurement of cutaneous metabolism have been designed to evaluate qualitative changes in the oxyhemoglobin volume, deoxyhemoglobin volume, and their sum (total Hb volume) relative to their baseline values. In this study, we developed an instrument for non-invasive evaluation of individual and regional differences in StO₂ and Hb volume, a system unaffected by melanin (Kao PSA system model III), and examined the validity of its application. First, changes in StO₂ and total Hb volume in the antebrachial region during venous occlusion and devascularization by compression of the brachial region were evaluated. Changes in total Hb volume following venous occlusion were found to reflect the cutaneous blood flow. Also, StO₂ was considered to reflect the state of oxygen consumption by the skin, because it was markedly reduced during devascularization. Next, the subjects were exposed to graded hypobaric conditions, and the relationships among StO₂, arterial blood oxygen saturation (SaO₂), and venous blood oxygen saturation (SvO₂) were studied. StO₂ showed significant positive correlations with SaO₂ (r=0.811, P<0.001) and SvO₂ (r=0.966, P<0.001), and its correlation with SvO₂ was particularly strong. Therefore, StO₂ was found to be closely dependent on SvO₂. Lastly, StO₂, total Hb volume, and other parameters were measured in healthy women (aged 20–69 years), and their regional differences and age- associated changes were evaluated. These regional differences (angle of mouth > cheek > forehead) and age-associated decreases in StO₂ are considered to be caused by the age-associated decreases in the cutaneous blood flow. Received: 21 May 1999 / Revised: 19 November 1999 / Accepted: 24 November 1999     

Oxygen supply in disposable shake-flasks: prediction of oxygen transfer rate, oxygen saturation and maximum cell concentration during aerobic growth

Dissolved oxygen plays an essential role in aerobic cultivation especially due to its low solubility. Under unfavorable conditions of mixing and vessel geometry it can become limiting. This, however, is difficult to predict and thus the right choice for an optimal experimental set-up is challenging. To overcome this, we developed a method which allows a robust prediction of the dissolved oxygen concentration during aerobic growth. This integrates newly established mathematical correlations for the determination of the volumetric gas–liquid mass transfer coefficient (k_La) in disposable shake-flasks from the filling volume, the vessel size and the agitation speed. Tested for the industrial production organism Corynebacterium glutamicum, this enabled a reliable design of culture conditions and allowed to predict the maximum possible cell concentration without oxygen limitation.     

Effects of assuming constant optical scattering on measurements of muscle oxygenation by near-infrared spectroscopy during exercise.

The aim of this study was to examine the effects of assuming constant reduced scattering coefficient (mu'(s)) on the muscle oxygenation response to incremental exercise and its recovery kinetics. Fifteen subjects (age: 24 +/- 5 yr) underwent incremental cycling exercise. Frequency domain near-infrared spectroscopy (NIRS) was used to estimate deoxyhemoglobin concentration {[deoxy(Hb+Mb)]} (where Mb is myoglobin), oxyhemoglobin concentration {[oxy(Hb+Mb)]}, total Hb concentration (Total[Hb+Mb]), and tissue O(2) saturation (Sti(O(2))), incorporating both continuous measurements of mu'(s) and assuming constant mu'(s). When measuring mu'(s), we observed significant changes in NIRS variables at peak work rate Delta[deoxy(Hb+Mb)] (15.0 +/- 7.8 microM), Delta[oxy(Hb+Mb)] (-4.8 +/- 5.8 microM), DeltaTotal[Hb+Mb] (10.9 +/- 8.4 microM), and DeltaSti(O(2))(-11.8 +/- 4.1%). Assuming constant mu'(s) resulted in greater (P < 0.01 vs. measured mu'(s)) changes in the NIRS variables at peak work rate, where Delta[deoxy(Hb+Mb)] = 24.5 +/- 15.6 microM, Delta[oxy(Hb+Mb)] = -9.7 +/- 8.2 microM, DeltaTotal[Hb+Mb] = 14.8 +/- 8.7 microM, and DeltaSti(O(2))= -18.7 +/- 8.4%. Regarding the recovery kinetics, the large 95% confidence intervals (CI) for the difference between those determine measuring mu'(s) and assuming constant mu'(s) suggested poor agreement between methods. For the mean response time (MRT), which describes the overall kinetics, the 95% confidence intervals were MRT - [deoxy(Hb+Mb)] = 26.7 s; MRT - [oxy(Hb+Mb)] = 11.8 s, and MRT - Sti(O(2))= 11.8 s. In conclusion, mu'(s) changed from light to peak exercise. Furthermore, assuming a constant mu'(s) led to an overestimation of the changes in NIRS variables during exercise and distortion of the recovery kinetics.     

Morphology of bakers' yeast and dissolved oxygen saturation during fed-batch growth

By complementary use of freeze-etching and scanning electron microscopy techniques, the morphology of cytoplasmic membrane and mitochondria of bakers' yeast ( Saccharomyces cerevisiae ) was shown to be sensitive to momentary lack of dissolved oxygen in fed-batch growth medium. Cells grown under constant excess oxygenation had more invaginations on their cytoplasmic membranes and showed larger mitochondria as assessed from the dimensions of their giant mitochondria.     

Arterial oxygen saturation and breathing movements during the first year of life.

Sixteen healthy term infants underwent 12 hour tape recordings of arterial oxygen saturation (SaO2)(Nellcor N100 in beat to beat mode) and breathing movements at around 6 weeks, 3 and 6 months of age. Six of these infants had an additional recording at around their first birthday. Recordings were analysed throughout for pauses in breathing movements of greater than or equal to 4 s (apnoeic pauses), episodes in which SaO2 fell to 80% (desaturations), and (only during regular breathing) baseline SaO2. In the 16 infants studied at 6 weeks, 3 and 6 months, the median frequency of both apnoeic pauses (5.6, 5.7, and 6.1/h, respectively) and desaturations (0.7, 0.4 and 0.5/h, respectively) showed little change. The majority of desaturations followed an apnoeic pause (median 73.2, 86.2 and 93.8% of desaturations). The median proportion of apnoeic pauses followed by a desaturation did not change significantly (9.0, 7.5 and 9.1%), despite an increase in the proportion of apnoeic pauses of greater than or equal to 8 s in duration from 2.0% at 6 weeks to 5.3% at 3 months (P less than 0.01). Baseline SaO2 was 97.3% or higher in all recordings. Median baseline SaO2 increased from 99.6 to 99.9% between 6 weeks and 3 months (P less than 0.02) and remained unchanged thereafter. In the subgroup of infants studied also at one year of age, again no significant differences were found with increasing age in the frequency of either apnoeic pauses or desaturations. The data show that in healthy subjects no major changes occur between 6 weeks and 1 year of life in apnoeic pause frequency or arterial oxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

Dry immersion effects on the mechanisms of metaboreflex regulation of hemodynamics during exercise

The effects of four-day dry immersion on metaboreflex regulation of hemodynamics were evaluated during local static exercise (30% of the maximum voluntary contraction) of the calf plantar flexors. One group of immersed subjects received low-frequency electrostimulation of their leg muscles to decrease the immersion effect on the EMG of exercising muscles. Metaboreflex regulation was evaluated by comparison of cardiovascular responses to physical loads with and without post-exercise circulatory occlusion. Immersion slightly increased the heart rate (HR) and reduced the systolic blood pressure in resting subjects; however, it did not have a distinct effect on blood pressure (BP) and HR during exercise or metaboreflex potentiation of hemodynamic shifts.     

Higher arterial oxygen saturation during submaximal exercise in Bolivian Aymara compared to European sojourners and Europeans born and raised at high altitude

Arterial oxygen saturation (SaO(2)) was measured at 3,600-3,850 m by pulse oximetry at rest and during submaximal exercise in three study groups: 1) highland Aymara natives of the Bolivian altiplano (n = 25); 2) lowland European/North American sojourners to the highlands with at least 2 months of acclimatization time to 3,600 m (n = 27); and 3) subjects of European ancestry born and raised at 3,600 m (n = 22). Aymara subjects maintained approximately 1 percentage point higher SaO(2) during submaximal work up to 70% of their maximal work capacity, and showed a smaller rate of decline in SaO(2) with increasing work compared to both European study groups. The higher-exercise SaO(2) of Aymara compared to Europeans born and raised at 3,600 m suggests genetic adaptation. The two European study groups, who differed by exposure to high altitude during their growth and development period, did not show any significant difference in either resting or exercise SaO(2). This suggests that the developmental mode of adaptation is less important than the genetic mode of adaptation in determining exercise SaO(2). A weak correlation was detected (across study groups only) between the residual forced vital capacity (FVC) and the residual SaO(2) measured at the highest level of submaximal work output (P = 0.024, R = 0.26). While firm conclusions based on this correlation are problematic, it is suggested that a part of the higher SaO(2) observed in Aymara natives is due to a larger lung volume and pulmonary diffusion capacity for oxygen. Results from this study are compared to similar studies conducted with Tibetan natives, and are interpreted in light of recent quantitative genetic analyses conducted in both the Andes and Himalayas.     

Habitat saturation and the spatial evolutionary ecology of altruism

Under which ecological conditions should individuals help their neighbours? We investigate the effect of habitat saturation on the evolution of helping behaviours in a spatially structured population. We combine the formalisms of population genetics and spatial moment equations to tease out the effects of various physiological (direct benefits and costs of helping) and ecological parameters (such as the density of empty sites) on the selection gradient on helping. Our analysis highlights the crucial importance of demography for the evolution of helping behaviours. It shows that habitat saturation can have contrasting effects, depending on the form of competition (direct vs. indirect competition) and on the conditionality of helping. In our attempt to bridge the gap between spatial ecology and population genetics, we derive an expression for relatedness that takes into account both habitat saturation and the spatial structure of genetic variation. This analysis helps clarify discrepancies in the results obtained by previous theoretical studies. It also provides a theoretical framework taking into account the interplay between demography and kin selection, in which new biological questions can be explored.     

Short-term spatial and temporal variation of sediment oxygen dynamics in a tropical tidal salt flat

Short-term spatial and temporal heterogeneity of oxygen dynamics and net primary production were studied in a tree day diurnal variation at a tidal tropical salt flat in the estuarine system of Sepetiba/Guaratiba coastal plain, Rio de Janeiro, Brazil. Oxygen concentrations were measured in situ with high temporal and spatial resolution oxygen microsensors. The results showed a remarkable heterogeneity of both oxygen penetration depth (from 0.18 to 0.85 cm) and net primary production (from −0.085 to 0.115 μmol O₂ cm⁻² s⁻¹) at different stations and sampling periods. Fast variations in abiotic factors like salinity and light due to the variable rainy weather were possibly the drivers of the high heterogeneity. In conclusion, short-term temporal changes could have a remarkable influence in sediment microalgae primary production. Not considering these changes can lead to wrong conclusions concerning the role and importance of sediment microalgae on tidal salt flats.     

Partitioning the variation among spatial,temporal and environmental components in a multivariate data set

Abstract We propose a method of partitioning the variation in a multivariate set of data according to (i) environmental variables, (ii) variables describing the spatial structure in the data and (iii) temporal variables. This method is an extension of an existing method for partialling out the spatial component of environmental variation, using canonical analysis. Our proposed method extends this approach by including temporal variables in the analysis. Thus, the partitioning of variation for a data matrix of species’abundances or biomass can include, by our methodology, the following components: (1) pure environmental, (2) pure spatial, (3) pure temporal, (4) pure spatial component of environmental, (5) pure temporal component of environmental, (6) pure combined spatial/temporal component, (7) combined spatial/temporal component of environmental and (8) unexplained. In addition, permutation testing accompanying the analyses allows tests of significance for the relationship between the different components and the species data. We illustrate the method with a set of survey data of penaeid species (prawns) obtained on the far northern Great Barrier Reef, Australia. This extension is a useful tool for multivariate analysis of ecological data from surveys, where space, time and environment commonly overlap and are important influences on observed variation.     

Differential temporal and spatial progerin expression during closure of the ductus arteriosus in neonates

Closure of the ductus arteriosus (DA) at birth is essential for the transition from fetal to postnatal life. Before birth the DA bypasses the uninflated lungs by shunting blood from the pulmonary trunk into the systemic circulation. The molecular mechanism underlying DA closure and degeneration has not been fully elucidated, but is associated with apoptosis and cytolytic necrosis in the inner media and intima. We detected features of histology during DA degeneration that are comparable to Hutchinson Gilford Progeria syndrome and ageing. Immunohistochemistry on human fetal and neonatal DA, and aorta showed that lamin A/C was expressed in all layers of the vessel wall. As a novel finding we report that progerin, a splicing variant of lamin A/C was expressed almost selectively in the normal closing neonatal DA, from which we hypothesized that progerin is involved in DA closure. Progerin was detected in 16.2%±7.2 cells of the DA. Progerin-expressing cells were predominantly located in intima and inner media where cytolytic necrosis accompanied by apoptosis will develop. Concomitantly we found loss of α-smooth muscle actin as well as reduced lamin A/C expression compared to the fetal and non-closing DA. In cells of the adjacent aorta, that remains patent, progerin expression was only sporadically detected in 2.5%±1.5 of the cells. Data were substantiated by the detection of mRNA of progerin in the neonatal DA but not in the aorta, by PCR and sequencing analysis. The fetal DA and the non-closing persistent DA did not present with progerin expressing cells. Our analysis revealed that the spatiotemporal expression of lamin A/C and progerin in the neonatal DA was mutually exclusive. We suggest that activation of LMNA alternative splicing is involved in vascular remodeling in the circulatory system during normal neonatal DA closure.     

A theory of measurement error and its implications for spatial and temporal gradient sensing during chemotaxis

Cells generally chemotax along a direction in which their receptor occupancy gradient—whether spatial or temporal—is maximum. Occupancy differentials are, however, often so small as to be masked by thermal noise; i.e., by fluctuations inherent in the stochastic nature of ligand binding. Such fluctuations therefore impose a fundamental limit on the sensitivity of a cell's ability to detect a chemoattractant gradient. In order to pursue the implications of this limit, fluctuation theories have been developed. The theories assume that the signal is some function of the receptor occupancy gradient, allow an estimate of the standard deviation abouts the mean signal, and permit an evaluation of, among other things, the extent to which a receptor defect can impair an effective response. Previous theories have assumed an equilibrated ligand-receptor interaction. In this paper we introduce a generalized definition of a signal caused by a receptor occupancy gradient that allows us to develop a non-equilibrium theory of thermal noise. We show that previous formulations are a special case of the current development. More specifically, we find the following.

1. Swimming cells subject to Brownian tumbling must generally average their signals over a very long time period to achieve a signal-to-noise ratio≤1. Spatial gradient detection is possible with ligand-receptor equilibrium constants<10³ M ^?1, but since such ligands are rare, theory predicts that tumbling cells will generally not detect gradients by measuring spatial occupancy differentials.These conclusions hold irrespective of whether chemical equilibrium is achieved.
2. For crawling cells not subject to Brownian tumbling, a range of affinities exists in which spatial or temporal gradient detection is possible. In general a spatial mechanism is more efficient for low affinity ligands (dissociation times <0.3s), whereas a temporal mechanism is more efficients for higherK. In this case the detection of gradients in slowly dissociating ligand will be facilitated if signal processing begins prior to chemical equilibration.
3. An important new parameter is indicated by the theory. The definitions of a temporal gradient signal is based on estimating and comparing average occupancy over two time intervals displaced by a timet ₁. The theory predicts an optimalt ₁, of order milliseconds, that leads to the shortest minimum averaging time.
4. Fort ₁ values at and longer than the optimum, and for all averaging times exceeding some minimum, the cell will detect a temporal signal.
5. For values oft ₁ at and near the optimum, if the averaging time becomes too long, the cell enters a region of insensitivity in which it can no longer respond.
6. Finally, as the interval between estimates of average occupancy decreases below the optimum, a critical value oft ₁ is reached at which the minimum averaging time undergoes an abrupt transition from a relatively short value to a value five orders of magnitude longer.

The molecular process(es) controllingt ₁ are at present unknown, nor has any attempt been made to identify them since the parameter has not been previously recognized. We speculate that the search for its molecular basis might uncover a highly sensitive control mechanism, with defects in this mechanism predicted to have a far more pronounced effect on the cells behavior than defects in receptor number or affinity.     

A theory of measurement error and its implications for spatial and temporal gradient sensing during chemotaxis

In order that cells respond to environmental cues, they must be able to measure ambient ligand concentration. Concentrations fluctuate, however, because of thermal noise, and one can readily show that estimates based on concentration values at a particular moment will be subject to substantial error. Cells are therefore expected to average their estimates over some limited time period. In this paper we assume that a cell uses fractional receptor occupancy as a measure of ambient ligand concentration and develop general expressions for the error a cell makes because the length of the averaging period is necessarily limited. Our analysis is general, relieving many of the assumptions underlying the seminal work of Berg and Purcell. The most important formal difference is our inclusion of occupancy-dependent dissociation--a phenomenon that has been well-documented for many systems. In addition, our formulation permits signal averaging to begin before chemical equilibrium has been established and it allows binding kinetics to be nonlinear (i.e., biomolecular rather than pseudo-first-order). The results are applied to spatial and temporal concentration gradients. In particular we estimate the minimum averaging times required for cells to detect such gradients under typical in vitro conditions. These estimates involve assigning numerical values to receptor ligand rate constants. If the rate constants are at their maximum possible values (limited only by center of mass diffusion), then either temporal or spatial gradients can be detected in minutes or less. If, however, as suggested by experiments, the rate constants are several orders of magnitude below their diffusion-limited values, then under typical constant gradient conditions the time required to detect a spatial gradient is prohibitively long, whereas temporal gradients can still be detected in reasonable lengths of time. This result was obtained for large cells such as lymphocytes, as well as for the smaller, bacterial cells. The ratio of averaging times for the two mechanisms--amounting to several orders of magnitude--is well beyond what could be reconciled by limitations of the calculation, and strongly suggests heavy reliance on temporal sensing mechanisms under typical in vitro conditions with constant spatial gradients.