Does chronic oral contraceptive use detrimentally affect C-reactive protein or iron status for endurance-trained women?

PURPOSE: Chronic use of the oral contraceptive pill (OCP) is reported to increase C-reactive protein (CRP) levels and increase the risk of cardiovascular disease in premenopausal females. METHODS: A secondary analysis of data from two research studies in eumenorrheic (n = 8) and OCP (n = 8) female athletes. Basal CRP and iron parameters were included in the analysis. Sample collection occurred following a standardized exercise and nutritional control for 24 h. Eumenorrheic females were tested in the early-follicular and mid-luteal phases, and the OCP users were tested in quasi-follicular and quasi-luteal phases (both active pill periods). RESULTS: A main effect for group (p < 0.01) indicated that average CRP concentration was higher in OCP users compared with eumenorrheic females, regardless of the day of measurement within the cycle. Results demonstrate a degree of iron parameters moderation throughout the menstrual cycle that is influenced by basal CRP levels; however, no linear relationship with CRP, serum iron, and ferritin was observed. CONCLUSIONS: Basal CRP values were consistently higher in the OCP group despite participants being in a rested state. These results may indicate a potential risk of cardiovascular disease in prolonged users of the OCP when compared to eumenorrheic female athletes.

Menthol as an Ergogenic Aid for the Tokyo 2021 Olympic Games: An Expert-Led Consensus Statement Using the Modified Delphi Method.

INTRODUCTION: Menthol topical application and mouth rinsing are ergogenic in hot environments, improving performance and perception, with differing effects on body temperature regulation. Consequently, athletes and federations are beginning to explore the possible benefits to elite sport performance for the Tokyo 2021 Olympics, which will take place in hot (~ 31 °C), humid (70% RH) conditions. There is no clear consensus on safe and effective menthol use for athletes, practitioners, or researchers. The present study addressed this shortfall by producing expert-led consensus recommendations. METHOD: Fourteen contributors were recruited following ethical approval. A three-step modified Delphi method was used for voting on 96 statements generated following literature consultation; 192 statements total (96/96 topical application/mouth rinsing). Round 1 contributors voted to "agree" or "disagree" with statements; 80% agreement was required to accept statements. In round 2, contributors voted to "support" or "change" their round 1 unaccepted statements, with knowledge of the extant voting from round 1. Round 3 contributors met to discuss voting against key remaining statements. RESULTS: Forty-seven statements reached consensus in round 1 (30/17 topical application/rinsing); 14 proved redundant. Six statements reached consensus in round 2 (2/4 topical application/rinsing); 116 statements proved redundant. Nine further statements were agreed in round 3 (6/3 topical application/rinsing) with caveats. DISCUSSION: Consensus was reached on 62 statements in total (38/24 topical application/rinsing), enabling the development of guidance on safe menthol administration, with a view to enhancing performance and perception in the heat without impairing body temperature regulation.

Effects of mild hypoxia in aviation on mood and complex cognition.

Thirty six volunteer air force personnel were sequentially exposed in a randomized balanced order in a hypobaric chamber to 30 min of baseline (sea level) and mild hypoxia induced by a specified altitude (sea level, 8000 ft and 12,000 ft), followed immediately by breathing 100% oxygen from an oro-nasal mask. Mood and complex cognition were assessed. Analysis of variance indicated that mood (fatigue and vigour) remained the same at 8000 ft but fatigue was increased (p = 0.001) and vigour reduced (p = 0.035) at 12,000 ft and was restored by supplementary oxygen. Complex cognition was not significantly altered by the test conditions. The results of this study do not support prior evidence that mild hypoxia equivalent to either 8000 or 12,000 ft, impairs complex cognition, but suggests that some aspects of mood may be affected at 12,000 ft and can be restored by breathing 100% oxygen.

A reliable preloaded cycling time trial for use in conditions of significant thermal stress.

The purpose of this study was to assess the reliability of a 15-min time trial preloaded with 45 min of fixed-intensity cycling under laboratory conditions of thermal stress. Eight trained cyclists/triathletes (41 ± 10 years, VO2 peak: 69 ± 8 mL/kg/min, peak aerobic power: 391 ± 72 W) completed three trials (the first a familiarization) where they cycled at ∼ 55% VO2 peak for 45 min followed by a 15-min time trial (∼75% VO2 peak) under conditions of significant thermal stress (WBGT: 26.7 ± 0.8 °C, frontal convective airflow: 20 km/h). Seven days separated the trials, which were conducted at the same time of day following 24 h of exercise and dietary control. Reliability increased when a familiarization trial was performed, with the resulting coefficient of variation and intraclass correlation coefficient of the work completed during the 15-min time trial, 3.6% and 0.96, respectively. Therefore, these results demonstrate a high level of reliability for a 15-min cycling time trial following a 45-min preload when performed under laboratory conditions of significant thermal stress using trained cyclists/triathletes.

Effects of hypoxia and hypercapnia on human HRV and respiratory sinus arrhythmia.

PURPOSE: Hypercapnia increases minute ventilation (V'E) with little effect on heart rate (HR), whereas hypoxia may increase HR without affecting V'E. However, the effects of hypercapnia and hypoxia on both heart rate variability(HRV) and the clustering of heart beats during spontaneous breathing (respiratory sinus arrhythmia ­ RSA), are not clear. METHODS: In this study, 10 human volunteers breathed room air (RA), hypercapnic (5% CO2) or hypoxic (10%O2) gas mixtures, each for 6 min, while resting supine. ECG, mean arterial pressure (MAP), ventilatory flow, inhaled and exhaled fractions of CO2 and O2, were recorded throughout. RESULTS: Both V'E and MAP increased with 5%CO2, with no change in HR. Hypoxia did not change ventilation but increased HR. High frequency components of HRV, and the relative proportion of heart beats occurring during inhalation increased with 5% CO2, but neither changed with 10% O2. CONCLUSION: Increased RSA concomitant with increased MAP suggests RSA ­ vagal dissociation with hypercapnia. Elevated heart rate with acute hypoxia with no change in either frequency components of HRV or the distribution of heart beats during ventilation, suggested that clustering of heart beats may not be a mechanism to improve ventilation-perfusion matching during hypoxia.

Does intermittent pneumatic leg compression enhance muscle recovery after strenuous eccentric exercise?

Intermittent pneumatic compression (IPC) has gained rapid popularity as a post-exercise recovery modality. Despite its widespread use and anecdotal claims for enhancing muscle recovery there is no scientific evidence to support its use. 10 healthy, active males performed a strenuous bout of eccentric exercise (3 sets of 100 repetitions) followed by IPC treatment or control performed immediately after exercise and at 24 and 48 h post-exercise. Muscular performance measurements were taken prior to exercise and 24, 48 and 72 h post-exercise and included single-leg vertical jump (VJ) and peak and average isometric [knee angle 75º] (ISO), concentric (CON) and eccentric (ECC) contractions performed at slow (30° · s⁻¹) and fast (180° · s⁻¹) velocities. Plasma creatine kinase (CK) samples were taken at pre- and post-exercise 24, 48 and 72 h. Strenuous eccentric exercise resulted in a significant decrease in peak ISO, peak and average CON (30° · s⁻¹) at 24 h compared to pre-exercise for both IPC and control, however VJ performance remained unchanged. There were no significant differences between conditions (IPC and control) or condition-time interactions for any of the contraction types (ISO, CON, ECC) or velocities (CON, ECC 30° · s⁻¹ and 180° · s⁻¹). However, CK was significantly elevated at 24 h compared to pre-exercise in both conditions (IPC and control). IPC did not attenuate muscle force loss following a bout of strenuous eccentric exercise in comparison to a control. While IPC has been used in the clinical setting to treat pathologic conditions, the parameters used to treat muscle damage following strenuous exercise in healthy participants are likely to be very different than those used to treat pathologic conditions.

Autonomic cardiovascular response to acute hypoxia and passive head-up tilting in humans.

Acute hypoxia may alter autonomic cardiovascular reflexes during orthostasis. Heart rate variability (HRV), arterial blood pressure (MAP), and respiratory sinus arrhythmia (RSA) were recorded during supine (SUP) and passive head up tilt (HUT) in eight healthy humans, spontaneously breathing either room air or 10% O2 in N2. In the time domain, heart rate increased and variability decreased with HUT in both trials, with no difference between trials. In the frequency domain, normalized low frequency HRV increased, and normalized high frequency HRV decreased with HUT in both trials, with no difference between trials. MAP was 74.9 (8.6) and 77.5 (11.7) mmHg when SUP in the room air and hypoxia trials, respectively. A significant increase in MAP occurred with HUT in the room air trial but not in the hypoxia trial. In both trials, end tidal CO2 decreased with HUT, with no difference between trials. In the room air trial, end tidal O2 increased with HUT, whereas during the hypoxia trial, end tidal O2 decreased with HUT. The distribution of heart beats relative to the phase of ventilation (%HBIN and %HBOUT) was similar in both trials: the %HBIN was 43.5 (3.3) % and %HBOUT was 56.5 (4.2) % breathing room air when SUP, and 45.5 (3.0) and 54.5 (3.2) when hypoxic and SUP. For both trials, this distribution did not change with HUT. As both HRV and RSA showed similar responses to HUT when spontaneously breathing either room air or 10% O2 in N2, we suggest that autonomic cardiovascular reflexes are preserved during acute hypoxia.

Human cardiac autonomic responses to head-up tilting during 72-h starvation.

Starvation may change autonomic nervous system activity and sensitivity such that a greater vagal withdrawal may occur during a sympathetic challenge. Six healthy humans endured a 3-day, water-only fast, during which participants were subjected to passive 80° head-up tilt testing twice on each day (a.m. and p.m.). Heart rate, heart rate variability (HRV), ventilation [Formula: see text], and respiration ([Formula: see text] and [Formula: see text]) were recorded during supine rest and head-up tilting. On Day 1 (a.m.), supine heart rate was 46.0 ± 3.3 beats min(-1), increasing to 51.6 ± 7.4 beats min(-1) on Day 3 (p.m.). On Day 1 (a.m.), supine high frequency HRV was 57.9 ± 31.6(NU), increasing to 69.5 ± 21.3(NU) on Day 3 (p.m.). Tilt-induced increases in heart rate were greater following starvation (10.5 ± 7.8 vs. 16.1 ± 8.6 beats min(-1)), and tilt-induced decreases in high frequency HRV were greater following starvation (-4.1 ± 27.7 vs. -28.0 ± 20.8(NU)). Supine V'CO(2) remained unchanged, whereas V'O(2) increased and respiratory exchange ratio decreased (0.91 ± 0.10 vs. 0.80 ± 0.05). Greater vagal withdrawal and elevated heart rate induced by head-up tilting during starvation may indicate increased autonomic sensitivity.

Indirect measures of human vagal withdrawal during head-up tilt with and without a respiratory acidosis.

Human ECG records were analyzed during supine (SUP) rest and whole body 80 degrees head-up tilt (HUT), with a respiratory acidosis (5%CO(2)) and breathing room air (RA). HUT increased heart rate in both conditions (RA(SUP) 60 +/- 13 vs. RA(HUT) 79 +/- 16; 5%CO(2SUP) 63 +/- 12 vs. 5%CO(2HUT) 79 +/- 14 beats min(-1)) and decreased mean R-R interval, with no changes in the R-R interval standard deviation. When corrected for changes in frequency spectrum total power (NU), the high frequency (0.15-0.4 Hz) component (HF(NU)) of heart rate variability decreased (RA(SUP) 44.01 +/- 21.57 vs. RA(HUT) 24.05 +/- 13.09; 5%CO(2SUP) 69.23 +/- 15.37 vs. 5%CO(2HUT) 47.64 +/- 21.11) without accompanying changes in the low frequency (0.04-0.15 Hz) component (LF(NU)) (RA(SUP) 52.36 +/- 21.93 vs. RA(HUT) 66.58 +/- 19.49; 5%CO(2SUP) 22.97 +/- 11.54 vs. 5%CO(2HUT) 40.45 +/- 21.41). Positive linear relations between the tilt-induced changes (Delta) in HF(NU) and R-R interval were recorded for RA (DeltaHF(NU) = 0.0787(DeltaR-R) - 11.3, R (2) = 0.79, P < 0.05), and for 5%CO(2) (DeltaHF(NU) = 0.0334(DeltaR-R) + 1.1, R (2) = 0.82, P < 0.05). The decreased HF component suggested withdrawal of vagal activity during HUT. For both RA and 5%CO(2), the positive linear relations between DeltaHF(NU) and DeltaR-R suggested that the greater the increase in heart rate with HUT, the greater the vagal withdrawal. However, a reduced range of DeltaHF during HUT with respiratory acidosis suggested vagal withdrawal was lower with a respiratory acidosis.

The effects of acute whole body vibration as a recovery modality following high-intensity interval training in well-trained, middle-aged runners.

The main purpose of the present study was to examine the effects of acute whole body vibration (WBV) on recovery following a 3 km time trial (3 km TT) and high-intensity interval training (HIIT) (8 x 400 m). Post-HIIT measures included 3 km time-trial performance, exercise metabolism and markers of muscle damage (creatine kinase, CK) and inflammation (c-reactive protein, CRP). A second purpose was to determine the effects of a 3 km TT and HIIT on performance and metabolism the following day. Nine well-trained, middle-aged, male runners [(mean +/- SD) age 45 +/- 6 years, body mass 75 +/- 7 kg, VO2peak 58 +/- 5 ml kg(-1 )min(-1)] performed a constant pace run at 60 and 80% velocity at VO2peak (v VO2peak) followed by a 3-km TT and a 8 x 400-m HIIT session on two occasions. Following one occasion, the athletes performed 2 x 15 min of low frequency (12 Hz) WBV, whilst the other occasion was a non-WBV control. Twenty-four hours after each HIIT session (day 2) participants performed the constant pace run (60 and 80% v VO2peak) and 3 km TT again. There was a significant decrease in 3 km TT performance (~10 s) 24 h after the HIIT session (P < 0.05); however, there were no differences between conditions (control vs. vibration, P > 0.05). Creatine kinase was significantly elevated on day 2, though there were no differences between conditions (P > 0.05). VO2peak and blood lactate were lower on day 2 (P < 0.05), again with no differences between conditions (P > 0.05). These results show no benefit of WBV on running performance recovery following a HIIT session. However, we have shown that there may be acute alterations in metabolism 24 h following such a running session in well-trained, middle-aged runners.

Human ventilatory efficiency and respiratory sinus arrhythmia during head-up tilt.

Cardiac vagal withdrawal when moving from supine to an upright posture may be independent of respiratory sinus arrhythmia. Further, ventilatory efficiency of an upright lung may improve with clustering of heart beats during inhalation. We studied healthy human subjects (n=8, 6 male) during supine rest (SUP) and 80 degrees head-up tilt (HUT). ECG and expired breath were sampled continuously to determine heart rate, mean and end-tidal (ET) fractional content (F) of O2 and CO2, tidal volume (V(T)) and breathing frequency (Bf). HUT increased heart rate (47+/-3 vs. 59+/-9 beats min(-1), p<0.01), decreased the high frequency component of heart rate variability (8.76+/- vs. 7.07+/-1.12, p<0.05), and increased the ratio of low to high frequency components in the heart rate (0.62+/-0.6 vs. 1.79+/-2.07, p<0.05). HUT did not change VT, Bf, or minute ventilation (V'E), but decreased FCO2 (4.90+/-0.48 vs. 4.56+/-0.42 %, p<0.05) and FETCO2 (6.64+/-0.24 vs. 6.30+/-0.27 %, p<0.01). HUT increased the CO2 ventilatory equivalent (24.88+/-2.50 vs. 26.74+/-2.61, p<0.01). Mean heart rate during inhalation increased with HUT (26+/-3 vs. 34+/-6 beats min-1), with no change during exhalation. Increased clustering of heart beats during inhalation independent of a decrease in HF cardiac variability may partly offset decreases in ventilatory efficiency of an upright lung.

Cardiac vagal control and respiratory sinus arrhythmia during hypercapnia in humans.

Normoxic hypercapnia may increase high-frequency (HF) power in heart rate variability (HRV) and also increase respiratory sinus arrhythmia (RSA). Low-frequency (LF) power may remain unchanged. In this study, 5-min ECG recordings (N = 10) were analyzed in time and frequency domains while human subjects breathed normoxic 5% CO2 (5%CO2) or room air (RA). Tidal volume (VT), inhalatory (TI), and exhalatory (TE) times of breaths in the final minute were measured. ECG time domain measures were unaffected by CO2 inhalation (P > 0.05). Following natural logarithmic transformation (LN), LFLN was unaltered (RA: 7.14 +/- 0.95 vs. 5%CO2: 7.35 +/- 1.12, P > 0.05), and HFLN increased (RA: 7.65 +/- 1.37 vs. 5%CO2: 8.58 +/- 1.11, P < 0.05) with CO2 inhalation. When changes in total power (NU) were corrected, LF(NU) decreased (RA: 34.4 +/- 22.9 vs. 5%CO2: 23.8 +/- 23.1, P < 0.01), and HFNU increased (RA: 56.5 +/- 22.3 vs. 5%CO2: 66.8 +/- 22.9, P < 0.01) with CO2 inhalation. TI (RA: 2.0 +/- 1.0 vs. 5%CO2: 1.9 +/- 0.8 s) and TE (RA: 2.5 +/- 1.1 vs. 5%CO2: 2.4 +/- 0.9 s) remained unchanged, but VT increased with CO2 inhalation (RA: 1.1 +/- 0.3 vs. 5%CO2: 2.0 +/- 0.8 L, P < 0.001). Heart rates during inhalation (RA: 35.2 +/- 4.4, 5%CO2: 34.5 +/- 4.8 beats min(-1)) were different from heart rates during exhalation (RA: 28.8 +/- 4.4, 5%CO2: 29.1 +/- 3.1 beats min(-1)). Hypercapnia did not increase the clustering of heart beats during inhalation, and we suggest that the HF component may not adequately reflect RSA.

Ganglioside GM2-activator protein and vesicular transport in collecting duct intercalated cells.

This study describes the molecular characterization of an antigen defined by an autoantibody from a woman with habitual abortion as GM2-activator protein. The patient showed no disorder of renal function. Accidentally with routine serum screening for autoantibodies, an immunoreactivity was found in kidney collecting duct intercalated cells. Three distinct patterns of immunostaining of intercalated cells were observed: staining of the apical pole, basolateral pole, and diffuse cytoplasmic labeling. Ultrastructurally, the immunoreactivity was associated with "studs," which represent the cytoplasmic domain of the vacuolar proton pump in intercalated cells. This pump is subjected to a shuttling mechanism from cytoplasmic stores to the cell membrane, which exclusively occurs in intercalated cells. Peptide sequences of a 23-kD protein purified from rat kidney cortex showed complete identity with corresponding sequences of GM2-activator protein. In the brain, GM2-activator protein is required for hexosaminidase A to split a sugar from ganglioside GM2. Because neither ganglioside GM2 nor GM1 (its precursor) is present in significant amounts in the kidney, the previous finding that this tissue contains the highest level of activator protein in the body was confusing. In this study, a novel role for GM2-activator protein in intercalated cells is proposed, and possible roles in the shuttling mechanism are discussed.

Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes.

Synaptopodin is an actin-associated protein of differentiated podocytes that also occurs as part of the actin cytoskeleton of postsynaptic densities (PSD) and associated dendritic spines in a subpopulation of exclusively telencephalic synapses. Amino acid sequences determined in purified rat kidney and forebrain synaptopodin and derived from human and mouse brain cDNA clones show no significant homology to any known protein. In particular, synaptopodin does not contain functional domains found in receptor-clustering PSD proteins. The open reading frame of synaptopodin encodes a polypeptide with a calculated Mr of 73.7 kD (human)/74.0 kD (mouse) and an isoelectric point of 9.38 (human)/9. 27 (mouse). Synaptopodin contains a high amount of proline ( approximately 20%) equally distributed along the protein, thus virtually excluding the formation of any globular domain. Sequence comparison between human and mouse synaptopodin revealed 84% identity at the protein level. In both brain and kidney, in vivo and in vitro, synaptopodin gene expression is differentiation dependent. During postnatal maturation of rat brain, synaptopodin is first detected by Western blot analysis at day 15 and reaches maximum expression in the adult animal. The exclusive synaptopodin synthesis in the telencephalon has been confirmed by in situ hybridization, where synaptopodin mRNA is only found in perikarya of the olfactory bulb, cerebral cortex, striatum, and hippocampus, i.e., the expression is restricted to areas of high synaptic plasticity. From these results and experiments with cultured cells we conclude that synaptopodin represents a novel kind of proline-rich, actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and podocyte foot processes.

A mechanism for heterogeneous endothelial responses to flow in vivo and in vitro.

Exposure of endothelium to a nominally uniform flow field in vivo and in vitro frequently results in a heterogeneous distribution of individual cell responses. Extremes in response levels are often noted in neighboring cells. Such variations are important for the spatial interpretation of vascular responses to flow and for an understanding of mechanotransduction mechanisms at the level of single cells. We propose that variations of local forces defined by the cell surface geometry contribute to these differences. Atomic force microscopy measurements of cell surface topography in living endothelium both in vitro and in situ combined with computational fluid dynamics demonstrated large cell-to-cell variations in the distribution of flow-generated shear stresses at the endothelial luminal surface. The distribution of forces throughout the surface of individual cells of the monolayer was also found to vary considerably and to be defined by the surface geometry. We conclude that the endothelial three-dimensional surface geometry defines the detailed distribution of shear stresses and gradients at the single cell level, and that there are large variations in force magnitude and distribution between neighboring cells. The measurements support a topographic basis for differential endothelial responses to flow observed in vivo and in vitro. Included in these studies are the first preliminary measurements of the living endothelial cell surface in an intact artery.

Subcellular distribution of shear stress at the surface of flow-aligned and nonaligned endothelial monolayers.

The stresses acting on the luminal surface of endothelial cells due to shear flow were determined on a subcellular scale. Atomic force microscopy was used to measure the surface topography of confluent endothelial monolayers cultured under no-flow conditions or exposed to steady shear stress (12 dyn/cm2 for 24 h). Flow over these surface geometries was simulated by computational fluid dynamics, and the distribution of shear stress on the cell surface was calculated. Flow perturbations due to the undulating surface produced cell-scale variations of shear stress magnitude and hence large shear stress gradients. Reorganization of the endothelial surface in response to prolonged exposure to steady flow resulted in significant reductions in the peak shear stresses and shear stress gradients. From the relationship between surface geometry and the resulting shear stress distribution, we have defined a hydrodynamic shape factor that characterizes the three-dimensional morphological response of endothelial cells to flow. The analysis provides a complete description of the spatial distribution of stresses on individual endothelial cells within a confluent monolayer on a scale relevant to the study of physical mechanisms of mechanotransduction.

Beta-adrenergic receptors and oxygen transport.

We investigated whether stimulation of baboon erythrocyte beta-adrenoreceptors affects oxygen transport by haemoglobin. To assess oxygen transport we measured the PO2 at which the haemoglobin was 50% saturated (P50) and the Hill parameter 'n'. Blood at PO2s ranging from 10 to 90 mm Hg was exposed to a 10(-3) M concentration of the agonists l-isoproterenol, l-epinephrine and l-norepinephrine in the presence and absence of 10(-5) M dl-propranolol. None of the adrenergic agents which were used in these experiments produced significant changes in either 'n' or P50 and the concentrations of 2,3-diphosphoglycerate and lactate were not altered by the agonists. We conclude from these results that short-term adrenergic stimulation of the baboon erythrocyte beta-adrenoreceptor does not affect factors known to influence oxygen transport, oxygen delivery or haemoglobin itself.