Mathias Steinach

Erythropoietin regulations in humans under different environmental and experimental conditions

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Circadian rhythms in bed rest: Monitoring core body temperature via heat-flux approach is superior to skin surface temperature

ABSTRACT Continuous recordings of core body temperature (CBT) are a well-established approach in describing circadian rhythms. Given the discomfort of invasive CBT measurement techniques, the use of skin temperature recordings has been proposed as a surrogate. More recently, we proposed a heat-flux approach (the so-called Double Sensor) for monitoring CBT. Studies investigating the reliability of the heat-flux approach over a 24-hour period, as well as comparisons with skin temperature recordings, are however lacking. The first aim of the study was therefore to compare rectal, skin, and heat-flux temperature recordings for monitoring circadian rhythm. In addition, to assess the optimal placement of sensor probes, we also investigated the effect of different anatomical measurement sites, i.e. sensor probes positioned at the forehead vs. the sternum. Data were collected as part of the Berlin BedRest study (BBR2-2) under controlled, standardized, and thermoneutral conditions. 24-hours temperature data of seven healthy males were collected after 50 days of -6° head-down tilt bed-rest. Mean Pearson correlation coefficients indicated a high association between rectal and forehead temperature recordings (r > 0.80 for skin and Double Sensor). In contrast, only a poor to moderate relationship was observed for sensors positioned at the sternum (r = -0.02 and r = 0.52 for skin and Double Sensor, respectively). Cross-correlation analyses further confirmed the feasibility of the forehead as a preferred monitoring site. The phase difference between forehead Double Sensor and rectal recordings was not statistically different from zero (p = 0.313), and was significantly smaller than the phase difference between forehead skin and rectal temperatures (p = 0.016). These findings were substantiated by cosinor analyses, revealing significant differences for mesor, amplitude, and acrophase between rectal and forehead skin temperature recordings, but not between forehead Double Sensor and rectal temperature measurements. Finally, Bland-Altman analysis indicated narrower limits of agreement for rhythm parameters between rectal and Double Sensor measurements compared to between rectal and skin recordings, irrespective of the measurement site (i.e. forehead, sternum). Based on these data we conclude that (1) Double Sensor recordings are significantly superior to skin temperature measurements for non-invasively assessing the circadian rhythm of rectal temperature, and (2) temperature rhythms from the sternum are less reliable than from the forehead. We suggest that forehead Double Sensor recordings may provide a surrogate for rectal temperature in circadian rhythm research, where constant routine protocols are applied. Future studies will be needed to assess the sensor’s ecological validity outside the laboratory under changing environmental and physiological conditions.

Temporal and spatial dispersion of human body temperature during deep hypothermia

BACKGROUND Clinical temperature management remains challenging. Choosing the right sensor location to determine the core body temperature is a particular matter of academic and clinical debate. This study aimed to investigate the relationship of measured temperatures at different sites during surgery in deep hypothermic patients. METHODS In this prospective single-centre study, we studied 24 patients undergoing cardiothoracic surgery: 12 in normothermia, 3 in mild, and 9 in deep hypothermia. Temperature recordings of a non-invasive heat flux sensor at the forehead were compared with the arterial outlet temperature of a heart-lung machine, with the temperature on a conventional vesical bladder thermistor and, for patients undergoing deep hypothermia, with oesophageal temperature. RESULTS Using a linear model for sensor comparison, the arterial outlet sensor showed a difference among the other sensor positions between -0.54 and -1.12°C. The 95% confidence interval ranged between 7.06 and 8.82°C for the upper limit and -8.14 and -10.62°C for the lower limit. Because of the hysteretic shape, the curves were divided into phases and fitted into a non-linear model according to time and placement of the sensors. During cooling and warming phases, a quadratic relationship could be observed among arterial, oesophageal, vesical, and cranial temperature recordings, with coefficients of determination ranging between 0.95 and 0.98 (standard errors of the estimate 0.69-1.12°C). CONCLUSION We suggest that measured surrogate temperatures as indices of the cerebral temperature (e.g. vesical bladder temperature) should be interpreted with respect to the temporal and spatial dispersion during cooling and rewarming phases.

Metabolic Responses to the Yukon Arctic Ultra: Longest and Coldest in the World.

Purpose The Yukon Arctic Ultra is considered the longest and coldest ultraendurance event in the world. Cold exposure and exercise has been reported to influence circulating levels of myokines, adipokines, and hepatokines that may influence considerable alterations in the regulation of metabolism. The purpose of the study was to evaluate the influence of the Yukon Arctic Ultra (430-mile event) on potential activators of brown fat, metabolites, and body composition in healthy individuals. Methods Eight male and female participants (mean ± SEM: age, 44 ± 3 yr; body mass index, 23.4 ± 0.9) were recruited for participation. Blood samples were collected at pre-event, mid-event, and post-event checkpoints. Results The temperature during the event ranged from −45°C to −8°C. Because of these extremely challenging conditions, 50% of the participants withdrew from competition by the 300-mile mark, and those that surpassed 300 miles lost a significant (P = 0.002; P = 0.01) amount of body weight (76 ± 5 kg to 73 ± 4 kg) and fat mass (13 ± 1 kg to 12 ± 3 kg), respectively. With respect to serum irisin, there was a trend (P = 0.06) toward significance from pre-event (1033 ± 88 ng·mL−1), mid-event (1265 ± 23 ng·mL−1) to post-event (1289 ± 24 ng·mL−1). Serum meteorin-like and fibroblast growth factor-21 remained stable throughout the event. There were no changes in creatinine, acetoacetate, acetate, and valine. Serum lactate decreased (P = 0.04) during the event. Conclusions The influence of cold exposure and extreme physical exertion may promote substantial increases in serum irisin, and specific alterations in substrate metabolism that largely preserve skeletal muscle and physiological resilience.

Sleep Quality Changes during Overwintering at the German Antarctic Stations Neumayer II and III: The Gender Factor.

Purpose Antarctic residence holds many challenges to human physiology, like increased psycho-social tension and altered circadian rhythm, known to influence sleep. We assessed changes in sleep patterns during 13 months of overwintering at the German Stations Neumayer II and III from 2008 to 2014, with focus on gender, as many previous investigations were inconclusive regarding gender-based differences or had only included men. Materials & Methods Time in bed, sleep time, sleep efficiency, number of arousals, sleep latency, sleep onset, sleep offset, and physical activity level were determined twice per month during seven overwintering campaigns of n = 54 participants (37 male, 17 female) using actimetry. Data were analyzed using polynomial regression and analysis of covariance for change over time with the covariates gender, inhabited station, overwintering season and influence of physical activity and local sunshine radiation. Results We found overall longer times in bed (p = 0.004) and sleep time (p = 0.014) for women. The covariate gender had a significant influence on time in bed (p<0.001), sleep time (p<0.001), number of arousals (p = 0.04), sleep latency (p = 0.04), and sleep onset (p<0.001). Women separately (p = 0.02), but not men (p = 0.165), showed a linear increase in number of arousals. Physical activity decreased over overwintering time for men (p = 0.003), but not for women (p = 0.174). The decline in local sunshine radiation led to a 48 minutes longer time in bed (p<0.001), 3.8% lower sleep efficiency (p<0.001), a delay of 32 minutes in sleep onset (p<0.001), a delay of 54 minutes in sleep offset (p<0.001), and 11% less daily energy expenditure (p<0.001), for all participants in reaction to the Antarctic winter’s darkness-phase. Conclusions Overwinterings at the Stations Neumayer II and III are associated with significant changes in sleep patterns, with dependences from overwintering time and local sunshine radiation. Gender appears to be an influence, as women showed a declining sleep quality, despite that their physical activity remained unchanged, suggesting other causes such as a higher susceptibility to psycho-social stress and changes in environmental circadian rhythm during long-term isolation in Antarctica.

Circadian Rhythm and Stress

Rhythmicity of physiological parameters is found in virtually all living systems. The circadian rhythm with its most obvious expression, the sleep–wake cycle, is closely tied to the diurnal rhythm of day and night. A disturbance of this highly regulated system can lead to circadian misalignment resulting in sleeping difficulties with consequences on many physiological functions like psychological and physical performance, the metabolism, and the immune system as it could be found in night shift workers or in people suffering from chronic jet lag. Stress in its many forms, generally perceived as an excessive demand on human psychological and/or physiological adaptive capabilities, can have a direct influence on the human sleeping pattern due to the integration of neuronal and hormonal pathways of the stress reaction and the circadian regulation. Thus excessive and/or chronic stress can lead to a disturbance of the circadian rhythm as it can be found in diseases like depression and posttraumatic stress disorder. Extreme environments such as high altitude, hot or cold environments, or microgravity also can alter human sleep patterns as well as during isolation and confinement – experimental setups that serve to simulate the isolated nature of long-term space travel.

Changes of 25-OH-Vitamin D during Overwintering at the German Antarctic Stations Neumayer II and III

Purpose Humans in Antarctica face different environmental challenges, such as low ultra-violet radiation, which is crucial for vitamin D production in humans. Therefore we assessed changes in 25-OH-vitamin D serum concentration during 13 months of overwintering at the German Stations Neumayer II and III (2007–2012). We hypothesized that (i) 25-OH-vitamin D serum concentration would significantly decrease, (ii) changes would be affected by age, gender, baseline (i.e. pre-overwintering) fat mass, baseline 25-OH-vitamin D serum concentration, and station residence, and (iii) our results would not differ from similar previous studies in comparable high latitudes. Materials & Methods 25-OH-vitamin D serum concentrations were determined before, after, and monthly during the campaigns from venous blood samples of n = 43 participants (28 men, 15 women). Baseline fat mass was determined via bio impedance analysis and body plethysmography. Data were analyzed for change over time, dependency on independent parameters, and after categorization for sufficiency (>50nmol/l), insufficiency (25-50nmol/l), and deficiency (<25nmol/l). Results were compared with data from similar previous studies. Results We found a significant decrease of 25-OH-vitamin D with dependency on month. Age, gender, fat mass, and station residence had no influence. Only baseline 25-OH-vitamin D serum concentrations significantly affected subsequent 25-OH-vitamin D values. Conclusions Overwinterings at the Antarctic German research stations Neumayer II and III are associated with a decrease in 25-OH-vitamin D serum concentrations, unaffected by age, gender, baseline fat mass, and station residence. Higher baseline vitamin D serum concentrations might protect from subsequent deficiencies. Residence at the Neumayer Stations may lead to lower vitamin D serum concentrations than found in other comparable high latitudes.

Chapter 3 – Exercise Physiology

Exercise physiology is the science of human performance under physical stress and the relationships between physical activity and the structure and function of the human body. From an evolutionary point of view, exercise physiology helps us to better understand human adaptational capabilities, and it provides valuable insights into today’s problems regarding the so-called “lifestyle diseases.” To this end, it demonstrates the complex interactions between metabolism, thermoregulation, and the cardiovascular, respiratory, and muscular systems. Adaptation processes in human endurance and strength through exercise training—or the lack thereof—can be quantified via different means of ergometry, allowing for comparison of athletic performance using standardized parameters such as maximum oxygen consumption. Applied exercise physiology also helps us to better understand the limits of human performance, especially when that performance takes place under challenging environmental conditions.

Cardiac Autonomic Modulations and Psychological Correlates in the Yukon Arctic Ultra: The Longest and the Coldest Ultramarathon

Studies on human physical performance in extreme environments have effectively approached the investigation of adaptation mechanisms and their physiological limits. As scientific interest in the interplay between physiological and psychological aspects of performance is growing, we aimed to investigate cardiac autonomic control, by means of heart rate variability, and psychological correlates, in competitors of a subarctic ultramarathon, taking place over a 690 km course (temperatures between +5 and −47°C). At baseline (PRE), after 277 km (D1), 383 km (D2), and post-race (POST, 690 km), heart rate (HR) recordings (supine, 15 min), psychometric measurements (Profile of Mood States/POMS, Borg fatigue, and Karolinska Sleepiness Scale scores both upon arrival and departure) were obtained in 16 competitors (12 men, 4 women, 38.6 ± 9.5 years). As not all participants reached the finish line, comparison of finishers (FIN, n = 10) and non-finishers (NON, n = 6), allowed differential assessment of performance. Resting HR increased overall significantly at D1 (FIN +15.9; NON +14.0 bpm), due to a significant decrease in parasympathetic drive. This decrease was in FIN only partially recovered toward POST. In FIN only, baseline HR was negatively correlated with mean velocity [r −0.63 (P.04)] and parasympathetic drive [pNN50+: r −0.67 (P.03)], a lower HR and a higher vagal tone predicting a better performance. Moreover, in FIN, a persistent increase of the long-term self-similarity coefficient, assessed by detrended fluctuation analysis (DFAα2), was retrieved, possibly due to higher alertness. As for psychometrics, at D1, POMS Vigor decreased (FIN: −7.0; NON: −3.8), while Fatigue augmented (FIN: +6.9; NON: +5.0). Sleepiness increased only in NON, while Borg scales did not exhibit changes. Baseline comparison of mood states with normative data for athletes displayed significantly higher positive mood in our athletes. Results show that: the race conditions induced early decreases in parasympathetic drive; the extent of vagal withdrawal, associated to the timing of its recovery, is crucial for success; pre-competition lower resting HR predicts a better performance; psychological profile is reliably depicted by POMS, but not by Borg fatigue scales. Therefore, assessment of heart rate variability and psychological profile may monitor and partly predict performance in long-duration ultramarathon in extreme cold environment.

Limb Skin Temperature as a Tool to Predict Orthostatic Instability

Orthostatic instability is one of the main consequences of weightlessness or gravity challenge and plays as well a crucial role in public health, being one of the most frequent disease of aging. Therefore, the assessment of effective countermeasures, or even the possibility to predict, and thus prevent orthostatic instability is of great importance. Heat stress affects orthostatic stability and may lead to impaired consciousness and decrease in cerebral perfusion, specifically during the exposure to G-forces. Conversely, peripheral cooling can prevent orthostatic intolerance – even in normothermic healthy subjects. Indicators of peripheral vasodilation, as elevated skin surface temperatures, may mirror blood decentralization and an increased risk of orthostatic instability. Therefore, the aim of this study was to quantify orthostatic instability risk, by assessing in 20 fighter jet pilot candidates’ cutaneous limb temperatures, with respect to the occurrence of G-force-induced almost loss of consciousness (ALOC), before and during exposure to a push-pull maneuver, i.e., head-down tilt, combined with lower body negative pressure. Peripheral skin temperatures from the upper and lower (both proximal and distal) extremities and core body temperature via heat-flux approach (i.e., the Double Sensor), were continuously measured before and during the maneuver. The 55% of subjects that suffered an ALOC during the procedure had higher upper arm and thigh temperatures at baseline compared to the 45% that remained stable. No difference in baseline core body temperature and distal limbs (both upper and lower) skin temperatures were found between the two groups. Therefore, peripheral skin temperature data could be considered a predicting factor for ALOC, prior to rapid onset acceleration. Moreover, these findings could also find applications in patient care settings such as in intensive care units.