Energy and time optimization during exit from torpor in vertebrate endotherms.

Torpor is used in small sized birds and mammals as an energy conservation trait. Considerable effort has been put towards elucidating the mechanisms underlying its entry and maintenance, but little attention has been paid regarding the exit. Firstly, we demonstrate that the arousal phase has a stereotyped dynamic: there is a sharp increase in metabolic rate followed by an increase in body temperature and, then, a damped oscillation in body temperature and metabolism. Moreover, the metabolic peak is around two-fold greater than the corresponding euthermic resting metabolic rate. We then hypothesized that either time or energy could be crucial variables to this event and constructed a model from a collection of first principles of physiology, control engineering and thermodynamics. From the model, we show that the stereotyped pattern of the arousal is a solution to save both time and energy. We extended the analysis to the scaling of the use of torpor by endotherms and show that variables related to the control system of body temperature emerge as relevant to the arousal dynamics. In this sense, the stereotyped dynamics of the arousal phase necessitates a certain profile of these variables which is not maintained as body size increases.

A thermodynamic-based approach to model the entry into metabolic depression by mammals and birds.

For decades, there was an intense debate in relation to the mechanism behind the entry into metabolic depression (EMD) of mammals and birds. The fulcrum of the argument was whether the depression of metabolic rate ([Formula: see text]) was caused by the drop in body temperature, the so-called "Q10 effect", or whether it was caused by a metabolic downregulation. One present-day model of this process is a qualitative (textual) description: the initial step of EDM would be a downregulation in [Formula: see text] from the value maintaining euthermia at a given ambient temperature to the basal metabolic rate of the animal and, then, Q10 effect would take over and drop [Formula: see text] to its lower levels. Despite widely accepted, this qualitative description still misses a theoretical analysis. Here, we transpose the descriptive model to a formal quantitative one and analyze it under necessary thermodynamic conditions of a system. We, then, compare the results of the formal model to empirical data of EMD by mammals and birds. The comparisons indicate that the metabolic evolution in the course of the entry phase does not follow the descriptive model. Instead, as proposed by alternate models, EMD is a downregulated process as a whole until a new equilibrium Tb is attained.

Post-decompression bubble and inflammation interactions: a non-extensive dynamical system model.

Inert gas bubbles in tissues and in blood have been historically considered as the only triggering factors for DCS, but now many other factors are considered to affect the final outcome of a decompression profile for a certain individual. In this sense, inflammation seems to play a relevant role, not only due to the physical damage of tissues by the bubbles, but as a potentiator of the process as a whole. The present study aims to put forward a mathematical model of bubble formation associated with an inflammatory process related to decompression. The model comprises four state-variables (inert gas pressure, inert gas bubbles, proinflammatory and inflammatory factors) in a set of non-linear differential equations. The model is non-extensive: inert gas transitions between liquid and gaseous phases do not change the concentration of the dissolved gas. The relationship between bubbles and inflammation is given through parameters that form a positive feedback loop. The results of the model were compared with the experimental results of echocardiography from volunteers in two dive/decompression profiles; the model shows a very good agreement with the empirical data and previews different inflammatory outcomes for different experimental profiles. We suggest that slight changes in the parameters' values might turn the simulations from a non-inflammatory to an inflammatory profile for a given individual. Therefore, the present model might help address the problem of DCS on a particular basis.

Association Between Heart Rate Variability and Decompression-Induced Physiological Stress.

The purpose of this study was to analyze the correlation between decompression-related physiological stress markers, given by inflammatory processes and immune system activation and changes in Heart Rate Variability, evaluating whether Heart Rate Variability can be used to estimate the physiological stress caused by the exposure to hyperbaric environments and subsequent decompression. A total of 28 volunteers participated in the experimental protocol. Electrocardiograms were performed; blood samples were obtained for the quantification of red cells, hemoglobin, hematocrit, neutrophils, lymphocytes, platelets, aspartate transaminase (AST), alanine aminotransferase (ALT), and for immunophenotyping and microparticles (MP) research through Flow Cytometry, before and after each experimental protocol from each volunteer. Also, myeloperoxidase (MPO) expression and microparticles (MPs) deriving from platelets, neutrophils and endothelial cells were quantified. Negative associations between the standard deviation of normal-to-normal intervals (SDNN) in the time domain, the High Frequency in the frequency domain and the total number of circulating microparticles was observed (p-value = 0.03 and p-value = 0.02, respectively). The pre and post exposure ratio of variation in the number of circulating microparticles was negatively correlated with SDNN (p-value = 0.01). Additionally, a model based on the utilization of Radial Basis Function Neural Networks (RBF-NN) was created and was able to predict the SDNN ratio of variation based on the variation of specific inflammatory markers (RMSE = 0.06).

Bouts of exercise elicit discordant testosterone: cortisol ratios in runners and non-runners.

OBJECTIVE: The testosterone:cortisol ratio (T:C) is suggested to be used in order to examine whether physical exercise generates either a "catabolic environment" or an "anabolic environment". The present study aims to evaluate the acute time-course profile of cortisol and testosterone due to an episode of physical exercise. A biphasic profile in the T:C ratio response was hypothesized. MATERIALS AND METHODS: Morning sessions of treadmill running at two different intensities (Heart Rate at 65% and 80% of the maximum cardiac reserve) were performed by 6 male non-runners (NR) and 12 trained male runners (subdivided into trained runners T1 and T2). Cortisol and testosterone were measured in saliva. NR and T1 ran for 30 minutes at both intensities, and T2 ran for 46 minutes (± 4.1) at 65% and 42 minutes (± 3.5) at 80%. RESULTS: In the 80% heart rate target, both groups of runners showed the biphasic time-profile, while the non-runners group did not. However, at the 65% level, none of the groups presented the hypothesized biphasic response. CONCLUSIONS: A biphasic time-profile in the testosterone:cortisol ratio can be seen in short-bout, high intensity exercise (treadmill running) during the morning in men trained for this specific physical activity.

Heart rate variability changes as an indicator of decompression-related physiological stress.

Many aspects of the physiological stress related to the exposure to the hyperbaric environment have been studied, but no research has been made to evaluate the impacts of scuba diving on heart rate variability (HRV). We investigated the effects of a simulated dive to 557 KPa (45 meters of salt water) for a 30-minute bottom time on the frequency and time domains estimators of HRV. Electrocardiogram records were obtained with superficial electrodes for 30 minutes before the simulated dive and, subsequently, for one hour after the dive. Each of these time-series was then subdivided into non-overlapping windows of 256 consecutive R-R intervals. A control group was submitted to the same protocol, breathing the same gases used in the simulated dive, while not being exposed to the hyperbaric environment. In the control group we observed a significant increase in SDNN (the square root of the variance of the R-R intervals), RMSSD (the square root of the mean squared differences of successive R-R intervals), and in two bands (high and low) of the power spectrum of frequencies. The subjects in the simulated dive presented only an increase in the low-frequency estimator without any further relevant changes in other estimators of HRV. This study suggests that the low-frequency increase without concomitant high-frequency increase might be an indicator of the physiological stress caused by decompression and that such a dissimilarity in responses might be correlated to the dive-related impairment of the endothelial function.

Bouts of exercise elicit discordant testosterone: cortisol ratios in runners and non-runners

ABSTRACT Objective: The testosterone:cortisol ratio (T:C) is suggested to be used in order to examine whether physical exercise generates either a "catabolic environment" or an "anabolic environment". The present study aims to evaluate the acute time-course profile of cortisol and testosterone due to an episode of physical exercise. A biphasic profile in the T:C ratio response was hypothesized. Materials and methods: Morning sessions of treadmill running at two different intensities (Heart Rate at 65% and 80% of the maximum cardiac reserve) were performed by 6 male non-runners (NR) and 12 trained male runners (subdivided into trained runners T1 and T2). Cortisol and testosterone were measured in saliva. NR and T1 ran for 30 minutes at both intensities, and T2 ran for 46 minutes (± 4.1) at 65% and 42 minutes (± 3.5) at 80%. Results: In the 80% heart rate target, both groups of runners showed the biphasic time-profile, while the non-runners group did not. However, at the 65% level, none of the groups presented the hypothesized biphasic response. Conclusions: A biphasic time-profile in the testosterone:cortisol ratio can be seen in short-bout, high intensity exercise (treadmill running) during the morning in men trained for this specific physical activity.

Frank-Starling mechanism and short-term adjustment of cardiac flow.

The Frank-Starling law of the heart is a filling-force mechanism (FFm), a positive relationship between the distension of a ventricular chamber and its force of ejection, and such a mechanism is found across all the studied vertebrate lineages. The functioning of the cardiovascular system is usually described by means of the cardiac and vascular functions, the former related to the contractility of the heart and the latter related to the afterload imposed on the ventricle. The crossing of these functions is the so-called 'operation point', and the FFm is supposed to play a stabilizing role for the short-term variations in the working of the system. In the present study, we analyze whether the FFm is truly responsible for such a stability within two different settings: one-ventricle and two-ventricle hearts. To approach the query, we linearized the region around an arbitrary operation point and put forward a dynamical system of differential equations to describe the relationship among volumes in face of blood flows governed by pressure differences between compartments. Our results show that the FFm is not necessary to give stability to an operation point. Thus, which forces selected and maintained such a mechanism in all vertebrates? The present results indicate three different and complementary roles for the FFm: (1) it decreases the demands of a central controlling system over the circulatory system; (2) it smooths out perturbations in volumes; and (3) it guarantees faster transitions between operation points, i.e. it allows for rapid changes in cardiac output.

Respiratory physiology of high-altitude anurans: 55 years of research on altitude and oxygen.

In a 1951 paper, perhaps the first one addressing adjustments of respiratory physiology in high-elevation anurans, L.C. Stuart tested the hypothesis that hemoglobin values were higher in the high-elevation Bufo bocourti than in the low-elevation species Bufo marinus. We use Stuart's paper as a starting point for a historical review of the field that encompasses the past 55 years. We start with the early search for evidence of physiological adjustments that took place in the 1960s, move to the studies with Telmatobius that dominated the 1970s and the 1980s, continue with the contributions of experimental physiology that characterized the 1990s, and finish with the discovery of mechanisms enhancing hemoglobin oxygen affinity in high-elevation anurans (2000s). When analyzing the last mentioned topic, we highlight the contributions by the late Professor Carlos Monge, to whom we dedicate this paper. Finally, we discuss the current state of the field, and propose directions for further studies.

Comparative biochemistry and physiology in Brazil: a critical appraisal.

Brazil stood out as the country with the highest number of submissions to the editorial project dedicated to Latin America by the journal Comparative Biochemistry and Physiology. Therefore, we felt that it was important to critically discuss the state of comparative biochemistry and physiology in this country. Our study is based on data collected from the ISI Web-of-Science. We analyzed publication trends through time, availability of novel approaches and techniques, patterns of collaboration among different geographical regions, patterns of collaboration with researchers abroad, and relative efforts dedicated to the study of biochemical and physiological adaptation of native fauna representing different terrestrial Brazilian biomes. Overall, our data shows that comparative biochemistry and physiology is a lively and productive discipline, but that some biases limit the scope of the field in Brazil. Some important limitations are the very heterogeneous distribution of research nuclei throughout the country and the absence of some important approaches, such as remote sensing and the use of molecular biology techniques in a comparative or evolutionary context. We also noticed that international collaboration far surpasses interregional collaboration, and discuss the possible causes and consequences of this situation. Finally, we found that Brazilian comparative biochemistry and physiology is biome-biased, as the Amazonian fauna has received far more attention than the whole pool of fauna representing other terrestrial biomes. We discuss the possible causes of these biases, and propose some directions that may contribute to invigorate the field in the country.

A critical understanding of the fractal model of metabolic scaling.

The exponent of the scaling of metabolic rate with body mass has been the subject of debate for more than a century. The argument is at two levels, one concerning questions of empirical support for the exponent and the other, how to derive it theoretically. At this second level, the exponent is usually treated as the outcome of an underlying physical burden and approached as the search for a natural law emerging within energetic and geometric constraints. Recently, a model relying on fractal geometry was proposed as a general explanation for the phenomenon. In the present study, a reanalysis of the fractal model is performed to verify its validity. All the conditions that allow for the connection between the geometric proposition and the allometric exponent are evaluated, as well as the energy loss minimization procedure put forward in the model. It is demonstrated that the minimization procedure is mathematically incorrect and ill-posed. Also, it is shown that none of the connecting conditions are fulfilled. Therefore, it is concluded that the fractal model lacks self-consistency and correct statement: it relies on strong assumptions of homogeneity in morpho-physiological features among organisms instead of demonstrating them, as claimed by its authors. It is proposed that empiricists and theoreticians should rather evaluate the frameworks for addressing metabolic scaling phenomena.

Control of metabolic rate is a hidden variable in the allometric scaling of homeotherms.

The allometric scaling exponent of the relationship between standard metabolic rate (SMR) and body mass for homeotherms has a long history and has been subject to much debate. Provided the external and internal conditions required to measure SMR are met, it is tacitly assumed that the metabolic rate (B) converges to SMR. If SMR does indeed represent a local minimum, then short-term regulatory control mechanisms should not operate to sustain it. This is a hidden assumption in many published articles aiming to explain the scaling exponent in terms of physical and morphological constraints. This paper discusses the findings of a minimalist body temperature (Tb) control model in which short-term controlling operations, related to the difference between Tb and the set-point temperatures by specific gains and time delays in the control loops, are described by a system of differential equations of Tb, B and thermal conductance. We found that because the gains in the control loops tend to increase as body size decreases (i.e. changes in B and thermal conductance are speeded-up in small homeotherms), the equilibrium point of the system potentially changes from asymptotically stable to a centre, transforming B and Tb in oscillating variables. Under these specific circumstances the very concept of SMR no longer makes sense. A series of empirical reports of metabolic rate in very small homeotherms supports this theoretical prediction, because in these animals B seems not to converge to a SMR value. We conclude that the unrestricted use of allometric equations to relate metabolic rate to body size might be misleading because metabolic control itself experiences size effects that are overlooked in ordinary allometric analysis.

Temperature effects on a whole metabolic reaction cannot be inferred from its components.

Changes in temperature affect the kinetic energy of the constituents of a system at the molecular level and have pervasive effects on the physiology of the whole organism. A mechanistic link between these levels of organization has been assumed and made explicit through the use of values of organismal Q10 to infer control of metabolic rate. To be valid this postulate requires linearity and independence of the isolated reaction steps, assumptions not accepted by all. We address this controversy by applying dynamic systems theory and metabolic control analysis to a metabolic pathway model. It is shown that temperature effects on isolated steps cannot rigorously be extrapolated to higher levels of organization.

Intraspecific relationships between resting and activity metabolism in anuran amphibians: influence of ecology and behavior.

The aerobic capacity model, as well as other models for the evolution of aerobic metabolism and the origin of endothermy, requires a mechanistic link between rates of resting and activity oxygen consumption (VO2rest and VO2act). The existence of such link is still controversial, but studies with anuran amphibians support a correlation between VO2rest and VO2act at both the intraspecific and interspecific levels. Because results at the intraspecific level are based only on a few species, we test for the generality of a link between these two metabolic variables in anurans by studying the intraspecific correlational patterns between mass-independent VO2rest and VO2act in anurans. We focus on 21 Neotropical species from different geographical areas that include remarkable diversity in behavior and thermal ecology. Although uncorrelated, VO2rest and VO2act seem to be consistent among individuals. Diverse intraspecific phenotypic correlational trends were detected, indicating that the intraspecific relationships between VO2rest and VO2act might be very diverse in anurans. The three possible trends (positive, negative, and absent correlations) were observed and appeared to be predictable from ecological and behavioral variables that relate to evolutionary physiological shifts in anurans. Positive correlations between VO2rest and VO2act were more common in species with active lifestyles (e.g., intense vocal activity) and in species that call at low temperatures (e.g., winter or high-elevation specialists).

Conditions for pathogen elimination by immune systems.

A continuous harvest effort can lead a population to extinction. How an "unconscious" immune system would perpetrate such an effort in order to eliminate a self-replicating antigen (a pathogen) becomes an intriguing problem if the system responses are functions of the pathogen population: the responses cannot be a continuous effort as the pathogen vanishes. On theoretical grounds, we show some qualities an immune response must have to support pathogen elimination. Then, three specific mechanisms are addressed: a pathogen-independent positive feedback loop among the responding cells of the system (e.g., B-lymphocyte and T-helper); the persistence of antigen bound to presenting cells; and the programmed expansion/contraction of a pool of responding cells. The maintenance of responding cells due to these mechanisms is the essential feature to the effective clearance of self-replicating agents. Thus, evolutionarily, the primary function of a helper lymphocyte would be to amplify a response and the primary function of memory would be the very elimination of pathogens.

A theoretical model for estimating the margination constant of leukocytes.

BACKGROUND: Blood leukocytes constitute two interchangeable sub-populations, the marginated and circulating pools. These two sub-compartments are found in normal conditions and are potentially affected by non-normal situations, either pathological or physiological. The dynamics between the compartments is governed by rate constants of margination (M) and return to circulation (R). Therefore, estimates of M and R may prove of great importance to a deeper understanding of many conditions. However, there has been a lack of formalism in order to approach such estimates. The few attempts to furnish an estimation of M and R neither rely on clearly stated models that precisely say which rate constant is under estimation nor recognize which factors may influence the estimation. RESULTS: The returning of the blood pools to a steady-state value after a perturbation (e.g., epinephrine injection) was modeled by a second-order differential equation. This equation has two eigenvalues, related to a fast- and to a slow-component of the dynamics. The model makes it possible to identify that these components are partitioned into three constants: R, M and SB; where SB is a time-invariant exit to tissues rate constant. Three examples of the computations are worked and a tentative estimation of R for mouse monocytes is presented. CONCLUSIONS: This study establishes a firm theoretical basis for the estimation of the rate constants of the dynamics between the blood sub-compartments of white cells. It shows, for the first time, that the estimation must also take into account the exit to tissues rate constant, SB.

Temperature effects on energy metabolism: a dynamic system analysis.

Q(10) factors are widely used as indicators of the magnitude of temperature-induced changes in physico-chemical and physiological rates. However, there is a long-standing debate concerning the extent to which Q(10) values can be used to derive conclusions about energy metabolism regulatory control. The main point of this disagreement is whether or not it is fair to use concepts derived from molecular theory in the integrative physiological responses of living organisms. We address this debate using a dynamic systems theory, and analyse the behaviour of a model at the organismal level. It is shown that typical Q(10) values cannot be used unambiguously to deduce metabolic rate regulatory control. Analytical constraints emerge due to the more formal and precise equation used to compute Q(10), derived from a reference system composed from the metabolic rate and the Q(10). Such an equation has more than one unknown variable and thus is unsolvable. This problem disappears only if the Q(10) is assumed to be a known parameter. Therefore, it is concluded that typical Q(10) calculations are inappropriate for addressing questions about the regulatory control of a metabolism unless the Q(10) values are considered to be true parameters whose values are known beforehand. We offer mathematical tools to analyse the regulatory control of a metabolism for those who are willing to accept such an assumption.