Cerebral blood flow regulation in hypobaric hypoxia: role of haemoconcentration.

During acute hypoxic exposure, cerebral blood flow (CBF) increases to compensate for the reduced arterial oxygen content (CaO2). Nevertheless, as exposure extends, both CaO2 and CBF progressively normalize. Haemoconcentration is the primary mechanism underlying the CaO2 restoration and may therefore explain, at least in part, the CBF normalization. Accordingly, we tested the hypothesis that reversing the haemoconcentration associated with extended hypoxic exposure returns CBF towards the values observed in acute hypoxia. Twenty-three healthy lowlanders (12 females) completed two identical 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in hypobaric hypoxia (HH, 3500 m). CBF was measured by ultrasound after 1, 6, 12, 48 and 96 h and compared between sojourns to assess the time course of changes in CBF. In addition, CBF was measured at the end of the HH sojourn after hypervolaemic haemodilution. Compared with NX, CBF was increased in HH after 1 h (P = 0.001) but similar at all later time points (all P > 0.199). Haemoglobin concentration was higher in HH than NX from 12 h to 96 h (all P < 0.001). While haemodilution reduced haemoglobin concentration from 14.8 ± 1.0 to 13.9 ± 1.2 g·dl-1 (P < 0.001), it did not increase CBF (974 ± 282 to 872 ± 200 ml·min-1; P = 0.135). We thus conclude that, at least at this moderate altitude, haemoconcentration is not the primary mechanism underlying CBF normalization with acclimatization. These data ostensibly reflect the fact that CBF regulation at high altitude is a complex process that integrates physiological variables beyond CaO2. KEY POINTS: Acute hypoxia causes an increase in cerebral blood flow (CBF). However, as exposure extends, CBF progressively normalizes. We investigated whether hypoxia-induced haemoconcentration contributes to the normalization of CBF during extended hypoxia. Following 4 days of hypobaric hypoxic exposure (corresponding to 3500 m altitude), we measured CBF before and after abolishing hypoxia-induced haemoconcentration by hypervolaemic haemodilution. Contrary to our hypothesis, the haemodilution did not increase CBF in hypoxia. Our findings do not support haemoconcentration as a stimulus for the CBF normalization during extended hypoxia.

Does Regular Physical Activity Mitigate the Age-Associated Decline in Pulmonary Function?

Whereas the negative effects of aging and smoking on pulmonary function are undisputed, the potential favorable effects of physical activity on the aging process of the otherwise healthy lung remain controversial. This question is of particular clinical relevance when reduced pulmonary function compromises aerobic exercise capacity (maximal oxygen consumption) and thus contributes to an increased risk of morbidity and mortality. Here, we discuss whether and when the aging-related decline in pulmonary function limits maximal oxygen consumption and whether, how, and to what extent regular physical activity can slow down this aging process and preserve pulmonary function and maximal oxygen consumption. Age-dependent effects of reduced pulmonary function (i.e., FEV1, the volume that has been exhaled after the first second of forced expiration) on maximal oxygen consumption have been observed in several cross-sectional and longitudinal studies. Complex interactions between aging-related cellular and molecular processes affecting the lung, and structural and functional deterioration of the cardiovascular and respiratory systems account for the concomitant decline in pulmonary function and maximal oxygen consumption. Consequently, if long-term regular physical activity mitigates some of the aging-related decline in pulmonary function (i.e., FEV1 decline), this could also prevent a steep fall in maximal oxygen consumption. In contrast to earlier research findings, recent large-scale longitudinal studies provide growing evidence for the beneficial effects of physical activity on FEV1. Although further confirmation of those effects is required, these findings provide powerful arguments to start and/or maintain regular physical activity.

5-Hydroxymethylfurfural and α-ketoglutaric acid supplementation increases oxygen saturation during prolonged exercise in normobaric hypoxia.

This double-blinded, randomized and placebo-controlled, crossover study investigated whether α-ketoglutaric-acid (α-KG) and 5-hydroxymethylfurfural (5-HMF) supplementation improves exercise performance in hypoxia and affects physiological responses during the exercise task. Eight moderately trained male participants (age: 25.3 ± 2.0 y, VO2max: 48.0 ± 8.3 ml/min/kg) performed an incremental exercise test to exhaustion in normoxia and two 2-hour cycle time trial (TT) tests in hypoxia (3,500 m) each separated by 1-week. Prior to the TT, participants supplemented with either α-KG and 5-HMF or placebo (random order). Supplementation did not improve TT performance at altitude and did not affect heart rate, effort perception and oxidative stress levels (p > 0.05). Oxygen saturation (SpO2) was enhanced during the α-KG and 5-HMF supplementation trial (79.5 ± 3.3 vs. 78.2 ± 3.7%, p = 0.026). Even though TT performance was unaffected, the enhanced SpO2 - possibly originated from changed O2-affinity - deserves further consideration as the exercise performance decline at altitude is strongly linked to the SpO2 decline. The inclusion of moderately fit participants, not specifically cycle trained, might have prevented any visible performance enhancement.

Venous Pooling in Suspension Syndrome Assessed with Ultrasound.

INTRODUCTION: Suspension syndrome describes a potentially life-threatening event during passive suspension on a rope. The pathophysiological mechanism is not fully understood; however, the most widespread hypothesis assumes blood pools in the lower extremities, prompting a reduction in cardiac preload and cardiac output and leading to tissue hypoperfusion, loss of consciousness, and death. The aim of this study was to assess venous pooling by ultrasound in simulated suspension syndrome using human subjects. METHODS: In this trial, 20 healthy volunteers were suspended in a sit harness for a maximum of 60 min with and without preceding exercise. Venous pooling was assessed by measuring the diameter of the superficial femoral vein (SFV) with ultrasound at baseline in supine and standing positions as well as during and after suspension. RESULTS: SFV diameter increased and blood flow became progressively sluggish. In 30% of the tests, near syncope occurred. However, SFV diameter did not differ between subjects with and without near syncope. CONCLUSIONS: Free hanging in a harness leads to rapid venous pooling in the lower limbs. The most important measure to prevent suspension syndrome might be constant movement of the legs.

Supervised Short-term High-intensity Training on Plasma Irisin Concentrations in Type 2 Diabetic Patients.

Irisin is a myokine involved in adipocyte transformation. Its main beneficial effects arise from increased energy expenditure. Irisin production is particularly stimulated by physical exercise. The present study investigates the changes of plasma irisin in type 2 diabetic patients performing 2 different training modalities. Fourteen type 2 diabetic patients underwent 4 week of supervised high-intensity interval training (HIT; n=8) or continuous moderate-intensity training (CMT; n=6), with equivalent total amounts of work required. Plasma samples were collected in the resting state atbaseline and one day after the exercise intervention to analyse resting plasma irisin, blood lipids, blood glucose, hsCRP, Adiponectin, Leptin and TNF-α concentrations. In addition, body composition and VO2peak were determined Resting plasma irisin increased after HIT (p=0.049) and correlated significantly with plasma fasting glucose at follow-up (r=0.763; p=0.006). CMT did not significantly change the amount of plasma irisin, although follow-up values of plasma irisin correlated negatively with fat-free mass (r=-0.827, p=0.002) and with fasting plasma glucose (r = - 0.934, p=0.006). Plasma irisin was found to increase with higher training intensity, confirming the assumption that exercise intensity, in addition to the type of exercise, may play an important role in the stimulation of the irisin response.

Acute effects of concentric and eccentric exercise matched for energy expenditure on glucose metabolism in healthy females: a randomized crossover trial.

BACKGROUND: Single bouts of muscle damaging eccentric exercise (EE) affect glucose metabolism negatively while single bouts of concentric (CE) and not muscle damaging eccentric exercise have positive acute short-term effects on glucose metabolism. It has been proposed that long-term endurance EE might be more effective in improving glucose metabolism than long-term CE when adjusted for energy expenditure. This would imply that adaptations of glucose metabolism are dependent on the type of exercise. Interleukin-6 (IL-6) released from the exercising muscles may be involved in and could therefore explain acute adaptations on glucose metabolism. The aim of the study was to investigate the effects of a single bout of CE and a single bout of EE inducing no or just mild muscle damage, matched for energy expenditure, on glucose metabolism. METHODS: 7 healthy but sedentary female participants (age 20.7 ± 2.9 years; BMI 22.45 ± 1.66 kg m(-2); VO2peak 39.0 ± 4.5 ml kg(-1) min(-1)) took part in a randomized cross over trial consisting of 1 h uphill (CE) respectively downhill (EE) walking on a treadmill. Venous blood samples were drawn before, directly after and 24 h after exercise. An oral glucose tolerance test (OGTT) was performed before and 24 h after exercise. RESULTS: CE and EE lead to comparable changes of glucose tolerance (area under the curve of the OGTT) (-16.0 ± 25.81 vs. -6.3 ± 45.26 mg dl(-1) h(-1), p = 1.000) and HOMA insulin resistance (-0.16 ± 1.53 vs. -0.08 ± 0.75, p = 0.753). Compared to baseline, IL-6 concentration increased significantly immediately after EE (1.07 ± 0.67 vs. 1.32 ± 0.60 pg ml(-1), p = 0.028) and tended to increase immediately after CE (0.75 ± 0.29 vs. 1.03 ± 0.21 pg ml(-1), p = 0.058). TNF-α concentration decreased significantly immediately after EE (1.47 ± 0.19 vs. 1.06 ± 0.29 pg ml(-1), p = 0.046) but not after CE (1.27 ± 0.43 vs. 1.24 ± 0.43 pg ml(-1), p = 0.686) compared to baseline. CONCLUSIONS: Acute effects of a single bout of exercise inducing no or just mild muscle damage on glucose tolerance and insulin resistance seem to be primarily energy expenditure dependent whereas acute anti-inflammatory activity induced by a single bout of exercise appears to be rather exercise type dependent. TRIAL REGISTRATION: NCT01890876, clinicaltrials.gov, https://clinicaltrials.gov/.

Effect of 3-week high-intensity interval training on VO2max, total haemoglobin mass, plasma and blood volume in well-trained athletes.

PURPOSE: This study examined the haematological adaptations to high-intensity interval training (HIT), i.e. total haemoglobin mass (tHb-mass), blood volume (BV), and plasma volume (PV), and its effects on VO2max in well-trained athletes. METHODS: Twenty-seven male and eight female well-trained (VO2max 63.7 ± 7.7 ml/min/kg) athletes were randomly assigned to the HIT (HITG, N = 19) or the control group (CG, N = 16). Over a 3-week period, the HITG performed 11 HIT sessions, consisting of four 4-min interval bouts at an exercise intensity of 90-95 % of the individual maximal heart rate (HRmax), separated by 4-min active recovery periods. Before and 5 ± 2 days after the intervention, tHb-mass, BV and PV were determined by the CO-rebreathing method. VO2max was assessed in a laboratory treadmill test. RESULTS: tHb-mass (from 753 ± 124 to 760 ± 121 g), BV (from 5.6 ± 0.8 to 5.6 ± 0.9 l) and PV (from 3.2 ± 0.5 to 3.2 ± 0.5 l) remained unchanged after HIT and did not show an interaction (group × time). Within the HITG, VO2max improved from baseline by +3.5 % (p = 0.011), but remained unchanged in the CG. No interaction (group × time) was seen for VO2max. The HITG showed a significant reduction in HRmax compared to the baseline measurement (-2.3 %, p ≤ 0.001), but HRmax remained unchanged in the CG. There was a significant interaction (group × time) for HRmax (p = 0.006). Also, oxygen pulse significantly increased only in HITG from 22.9 ± 4.4 to 23.9 ± 4.2 ml/beat, with no interaction (p = 0.150). CONCLUSIONS: Eleven HIT sessions added to usual training did neither improve VO2max nor haematological parameters compared to the CG.

Effects of antioxidant supplementation on exercise performance in acute normobaric hypoxia.

BACKGROUND/OBJECTIVES: To compare the effects of a 3-week supplementation between two different mixtures of antioxidants and placebo on aerobic exercise performance in acute normobaric hypoxia. SUBJECTS/METHODS: Seventeen subjects were randomly assigned in a double-blind fashion to receive a broad-based antioxidants supplement containing beta-carotene, ascorbic acid, d-alpha-tocopherol-succinate, N-acetylcysteine, riboflavin, zinc, and selenium (antioxidant capsule group [AO group]), or a combination of alpha-ketoglutaric acid (α-KG) and 5-hydroxymethylfurfural (5-HMF; CYL concentrate supplementation group [CS group]), or placebo (PL group). Before and after supplementation, subjects performed two incremental cycle-exercise tests until exhaustion. The first test was conducted under normoxic conditions (LA, FiO2 of 20.9%, ~547 m) and the second after the 3-week supplementation period under normobaric hypoxic conditions (AHA, FiO2 of 12.9%, ~4300m). RESULTS: In CS peak cycling performance (peak power) declined from LA to AHA 7.3% (90% CI: 2.2-12.4) less compared with PL (p = .04) and 6.7% (90%CI: 3.2-10.2) less compared with AO (p = .03). Better maintenance of aerobic exercise capacity in CS was associated with an attenuated reduction in maximal heart rate in hypoxia. CONCLUSIONS: Aerobic exercise performance was less impaired in acute normobaric hypoxia after 3 weeks with supplementation of α-KG and 5-HMF compared with a broad-based antioxidants supplement or PL.

High cardiorespiratory fitness is more beneficial in pre-diabetic men than women

OBJECTIVES: To investigate gender-specific relationships between cardiorespiratory fitness and factors that predict the development of diabetes and to identify the risk factors that predict fasting plasma glucose and 2-hour plasma glucose levels. INTRODUCTION: Different risk factors (e.g., low cardiorespiratory fitness) may cause elevated plasma glucose levels in men compared to women. Therefore, gender-specific analyses are needed. METHODS: Cardiorespiratory fitness (maximal power output achieved during a standard cycle ergometry test), resting blood pressure, total serum cholesterol, high-density lipoprotein cholesterol and triglyceride levels were measured in 32 pre-diabetic men (mean age: 57.2 + 6.8 years; mean body mass index (BMI): 28.5 + 3.0 kg/m²) and 40 pre-diabetic women (mean age: 55.0 + 7.3 years, mean BMI: 30.4+5.7 kg/m²). A stepwise regression with backward variable selection was performed to construct models that predict 2-hour and fasting plasma glucose levels. RESULTS: Maximal power output was inversely related to the 2-hour plasma glucose level in the entire group (r= -0.237, p<0.05), but this relationship was significant only for males (r= -0.404, p<0.05). No significant correlation was found between female gender and cardiorespiratory fitness. Age and cardiorespiratory fitness were significant predictors of 2-hour plasma glucose levels in men. High-density lipoprotein cholesterol was predictive of 2-hour plasma glucose levels in women. Triglycerides in women and BMI in men were the only predictors of fasting plasma glucose levels. CONCLUSIONS: These findings may have consequences for the development of gender-specific diabetes prevention programs. Whereas increasing cardiorespiratory fitness should be a key goal for men, improving the lipid profile seems to be more beneficial for women. However, the present results do not negate the positive effects of increasing cardiorespiratory fitness in women.