A randomized, cross-over trial assessing effects of beverage sodium concentration on plasma sodium concentration and plasma volume during prolonged exercise in the heat.

PURPOSE: This study assessed whether increasing sodium in a sports drink above that typical (~ 20 mmol L-1) affects plasma sodium and volume responses during prolonged exercise in the heat. METHODS: Endurance trained males (N = 11, 36 ± 14 y, 75.36 ± 5.30 kg, [Formula: see text]O2max 60 ± 3 mL min-1 kg-1) fulfilled requirements of the study including one 1-h exercise pre-trial, to estimate fluid losses (to prescribe fluid intake), and two, experimental trials (3-h or until tolerance), in random order, cycling (55% [Formula: see text]O2max, 34 °C, 65% RH). Beverages contained 6% carbohydrate and either 21 mmol L-1 (Low Na+) or 60 mmol L-1 sodium (High Na+). Analyses included linear mixed models and t-tests. RESULTS: Cycling time was similar 176 ± 9 min (Low Na+); 176 ± 7 min (High Na+). Fluid intake was 1.12 ± 0.19 L h-1; 1.14 ± 0.21 L h-1, resp. Body mass change was - 0.53 ± 0.40%; - 0.30 ± 0.45%, resp. Sodium intake was 69 ± 12 mmol; 201 ± 40 mmol, resp. Plasma sodium concentration was greater in High Na+ than Low Na+ (p < 0.001); decreasing in Low Na+ (- 1.5 ± 2.2 mmol L-1), increasing in High Na+ (0.8 ± 2.4 mmol L-1) (p = 0.048, 95% CI [- 4.52, - 0.02], d = 0.99). Plasma volume decreased in Low Na+ (- 2 ± 2%) but remained unchanged in High Na+ (0 ± 3%) (p = 0.01, 95% CI [- 3.2, - 0.5], d = 0.80). CONCLUSIONS: When conducting prolonged exercise in the heat, those who fully hydrate would benefit by increased sodium content of the beverage by improved plasma volume and sodium maintenance. Australian New Zealand Clinical Trials Registry (ACTRN12616000239460) 22/02/16.

Cardiopulmonary exercise testing in severe osteoarthritis: a crossover comparison of four exercise modalities.

Cardiopulmonary exercise testing is performed increasingly for cardiorespiratory fitness assessment and pre-operative risk stratification. Lower limb osteoarthritis is a common comorbidity in surgical patients, meaning traditional cycle ergometry-based cardiopulmonary exercise testing is difficult. The purpose of this study was to compare cardiopulmonary exercise testing variables and subjective responses in four different exercise modalities. In this crossover study, 15 patients with osteoarthritis scheduled for total hip or knee arthroplasty (mean (SD) age 68 (7) years; body mass index 31.4 (4.1) kg.m-2 ) completed cardiopulmonary exercise testing on a treadmill, elliptical cross-trainer, cycle and arm ergometer. Mean (SD) peak oxygen consumption was 20-30% greater on the lower limb modalities (treadmill 21.5 (4.6) (p < 0.001); elliptical cross-trainer (21.2 (4.1) (p < 0.001); and cycle ergometer (19.4 (4.2) ml.min-1 .kg-1 (p = 0.001), respectively) than on the arm ergometer (15.7 (3.7) ml.min-1 .kg-1 ). Anaerobic threshold was 25-50% greater on the lower limb modalities (treadmill 13.5 (3.1) (p < 0.001); elliptical cross-trainer 14.6 (3.0) (p < 0.001); and cycle ergometer 10.7 (2.9) (p = 0.003)) compared with the arm ergometer (8.4 (1.7) ml.min-1 .kg-1 ). The median (95%CI) difference between pre-exercise and peak-exercise pain scores was greater for tests on the treadmill (2.0 (0.0-5.0) (p = 0.001); elliptical cross-trainer (3.0 (2.0-4.0) (p = 0.001); and cycle ergometer (3.0 (1.0-5.0) (p = 0.001)), compared with the arm ergometer (0.0 (0.0-1.0) (p = 0.406)). Despite greater peak exercise pain, cardiopulmonary exercise testing modalities utilising the lower limbs affected by osteoarthritis elicited higher peak oxygen consumption and anaerobic threshold values compared with arm ergometry.

Indomethacin markedly blunts cerebral perfusion and reactivity, with little cognitive consequence in healthy young and older adults.

KEY POINTS: Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely-reduced cerebral blood flow (CBF) impairs cognition in healthy adults. In the present study, we used a placebo-controlled, single-blinded, randomized cross-over design to test the hypothesis that acutely-reduced CBF (using a pharmacological aid; indomethacin) would impair cognition in young and older healthy adults. At baseline, older adults had lower cognitive performance and CBF, but similar cerebrovascular reactivity to CO2 and dynamic cerebral autoregulation compared to young adults. In both young and older adults, cognitive performance on a mental switching task was slightly (7%) reduced after indomethacin, but not significantly associated with reductions in CBF (∼31%). These results indicate that cognitive performance is broadly resilient against a ∼31% reduction in CBF per se in healthy young and older adults. ABSTRACT: Cognitive function depends on adequate cerebrovascular perfusion and control. However, it is unknown whether acutely-reduced cerebral blood flow (CBF) impairs cognition in healthy adults. Using a placebo-controlled, single-blinded, randomized cross-over design, we tested the hypothesis that acutely-reduced CBF (using indomethacin [1.2 mg kg-1 oral dose]) would impair cognition in young (n = 13; 25 ± 4 years) and older (n = 12; 58 ± 6 years) healthy adults. CBF and cerebrovascular control were measured using middle cerebral artery blood velocity (MCAvmean ) and its reactivity to hypercapnia (CVRHYPER ) and hypocapnia (CVRHYPO ), respectively. Cognitive function was assessed using a computerized battery including response time tasks. Baseline comparisons revealed that older adults had 14% lower MCAvmean and 15% lower cognitive performance (all P ≤ 0.048), but not lower CVRHYPER/HYPO (P ≥ 0.26). Linear and rank-based mixed models revealed that indomethacin decreased MCAvmean by 31% (95% confidence interval = -35 to -26), CVRHYPER by 68% [interquartile range (IQR) = -94 to -44] and CVRHYPO by 50% (IQR = -83 to -33) (treatment-effect; all P < 0.01), regardless of age. Baseline CVRHYPER/HYPO values were strongly associated with their indomethacin-induced reductions (r = 0.70 to 0.89, P < 0.01). Mental switching performance was impaired 7% (IQR = 0-19) after indomethacin (P = 0.04), but not significantly associated with reductions in MCAvmean (Young: rho = -0.31, P = 0.30; Older: rho = 0.06, P = 0.86). In conclusion, indomethacin reduced MCAvmean and impaired cognition slightly; however, no clear association was evident in younger or older adults. Older adults had poorer cognition and lower MCAvmean , but similar CVRHYPER/HYPO .

Intrathecal drug delivery in the era of nanomedicine.

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress.

KEY POINTS: Thermal and hypoxic stress commonly coexist in environmental, occupational and clinical settings, yet how the brain tolerates these multi-stressor environments is unknown Core cooling by 1.0°C reduced cerebral blood flow (CBF) by 20-30% and cerebral oxygen delivery (CDO2 ) by 12-19% at sea level and high altitude, whereas core heating by 1.5°C did not reliably reduce CBF or CDO2 Oxygen content in arterial blood was fully restored with acclimatisation to 4330 m, but concurrent cold stress reduced CBF and CDO2 Gross indices of cognition were not impaired by any combination of thermal and hypoxic stress despite large reductions in CDO2 Chronic hypoxia renders the brain susceptible to large reductions in oxygen delivery with concurrent cold stress, which might make monitoring core temperature more important in this context ABSTRACT: Real-world settings are composed of multiple environmental stressors, yet the majority of research in environmental physiology investigates these stressors in isolation. The brain is central in both behavioural and physiological responses to threatening stimuli and, given its tight metabolic and haemodynamic requirements, is particularly susceptible to environmental stress. We measured cerebral blood flow (CBF, duplex ultrasound), cerebral oxygen delivery (CDO2 ), oesophageal temperature, and arterial blood gases during exposure to three commonly experienced environmental stressors - heat, cold and hypoxia - in isolation, and in combination. Twelve healthy male subjects (27 ± 11 years) underwent core cooling by 1.0°C and core heating by 1.5°C in randomised order at sea level; acute hypoxia ( PET,O2  = 50 mm Hg) was imposed at baseline and at each thermal extreme. Core cooling and heating protocols were repeated after 16 ± 4 days residing at 4330 m to investigate any interactions with high altitude acclimatisation. Cold stress decreased CBF by 20-30% and CDO2 by 12-19% (both P < 0.01) irrespective of altitude, whereas heating did not reliably change either CBF or CDO2 (both P > 0.08). The increases in CBF with acute hypoxia during thermal stress were appropriate to maintain CDO2 at normothermic, normoxic values. Reaction time was faster and slower by 6-9% with heating and cooling, respectively (both P < 0.01), but central (brain) processes were not impaired by any combination of environmental stressors. These findings highlight the powerful influence of core cooling in reducing CDO2 . Despite these large reductions in CDO2 with cold stress, gross indices of cognition remained stable.

Independent and interactive effects of incremental heat strain, orthostatic stress, and mild hypohydration on cerebral perfusion.

The purpose of this study was to identify the dose-dependent effects of heat strain and orthostasis [via lower body negative pressure (LBNP)], with and without mild hypohydration, on systemic function and cerebral perfusion. Eleven men (means ± SD: 27 ± 7 y; body mass 77 ± 6 kg), resting supine in a water-perfused suit, underwent progressive passive heating [0.5°C increments in core temperature (Tc; esophageal to +2.0°C)] while euhydrated (EUH) or hypohydrated (HYPO; 1.5-2% body mass deficit). At each thermal state, mean cerebral artery blood velocity (MCAvmean; transcranial Doppler), partial pressure of end-tidal carbon dioxide ([Formula: see text]), heart rate (HR) and mean arterial blood pressure (MAP; photoplethysmography) were measured continuously during LBNP (0, -15, -30, and -45 mmHg). Four subjects became intolerant before +2.0°C Tc, unrelated to hydration status. Without LBNP, decreases in [Formula: see text] accounted fully for reductions in MCAvmean across all Tc. With LBNP at heat tolerance (+1.5 or +2.0°C), [Formula: see text] accounted for 69 ± 25% of the change in MCAvmean. The HYPO condition did not affect MCAvmean or any cardiovascular variables during combined LBNP and passive heat stress (all P > 0.13). These findings indicate that hypocapnia accounted fully for the reduction in MCAvmean when passively heat stressed in the absence of LBNP and for two- thirds of the reduction when at heat tolerance combined with LBNP. Furthermore, when elevations in Tc are matched, mild hypohydration does not influence cerebrovascular or cardiovascular responses to LBNP, even when stressed by a combination of hyperthermia and LBNP.

Restricting dietary sodium reduces plasma sodium response to exercise in the heat.

Exercise-associated hyponatremia can be life-threatening. Excessive hypotonic fluid ingestion is the primary etiological factor but does not explain all variability. Possible effects of chronic sodium intake are unknown. The aim of this study was to determine whether dietary sodium affects plasma sodium concentration [Na+ ] during exercise in the heat, when water intake nearly matches mass loss. Endurance-trained men (n = 9) participated in this crossover experiment. Each followed a low-sodium (lowNa) or high-sodium (highNa) diet for 9 days with 24-h fluid intakes and urine outputs measured before experimental trials (day 10). The trials were ≥2 week apart. Trials comprised 3 h (or if not possible to complete, to exhaustion) cycling (55% VO2max ; 34 °C, 65% RH) with water intake approximating mass loss. Plasma [Na+ ], hematocrit, sweat and urine [Na+ ], heart rate, core temperature, and subjective perceptions were monitored. Urine [Na+ ] was lower on lowNa 24 h prior to (31 ± 24, 76 ± 30 mmol/L, P = 0.027) and during trials (10 ± 10, 52 ± 32 mmol/L, P = 0.004). Body mass was lower on lowNa (79.6 ± 8.5, 80.5 ± 8.9, P = 0.03). Plasma [Na+ ] was lower on lowNa before (137 ± 2, 140 ± 3, P = 0.007) and throughout exercise (P = 0.001). Sweat [Na+ ] was unaffected by diet (54.5 ± 40, 54.5 ± 23 mmol/L, P = 0.99). Heart rate and core temperature were higher on lowNa (P ≤ 0.001). Despite decreased urinary sodium losses, plasma sodium was lower on lowNa, with decreased mass indicating (extracellular) water may have been less, explaining greater heart rate and core temperature. General population health recommendations to lower salt intake may not be appropriate for endurance athletes, particularly those training in the heat.

Swimming in warm water is ineffective in heat acclimation and is non-ergogenic for swimmers.

Heat acclimation (HA) in air confers adaptations that improve exercise capabilities in hot and possibly temperate air. Swimmers may benefit from HA, yet immersion may constrain adaptation. Therefore, we examined whether warm-water swimming constitutes effective HA. In a randomized-crossover study, eight male swimmers swam 60 min/day on 7 days in 33 °C (HA) or 28 °C (CON) water. They performed 20-min distance trials before and after each regime: in 33 °C water (Warm); 28 °C water (Temperate); and cycling in 29 °C air (Terrestrial) following standardized exercise. Rectal temperature (Tre ) rose ∼ 1 °C in HA sessions, and sweat loss averaged 1.4 L/h. After accounting for CON, HA did not confer any clear expansion of plasma volume [1.9% (95% CI: 7.7)], reduction in heart rate during standardized cycling exercise [1 b/min (9)], reduction in Tre during rest [+0.1 °C (0.1)] or exercise, or change in sudomotor function. Only perceived temperature and discomfort tended to improve. Performance was clearly not improved for Warm [+0.3% (1.8)] or Temperate [+0.3% (1.9)], was unclear for Terrestrial [+0.4% (17.7)], and was unrelated to changes in resting plasma volume (r < 0.3). In conclusion, short-term HA using swimming in 33 °C water confers little adaptation and is not ergogenic for warm or temperate conditions.

Cerebrovascular responses during rowing: Do circadian rhythms explain morning and afternoon performance differences?

The purpose of this study was to characterize cerebrovascular responses to rowing exercise, investigating whether their diurnal variation might explain performance differences across a day. Twelve male rowers completed incremental rowing exercise and a 2000-m ergometer time trial at 07:00 h and 16:00 h, 1 week apart, while middle cerebral artery velocity (MCAv), cerebral (prefrontal), and muscular (vastus lateralis) tissue oxygenation and hemoglobin volume (via near-infrared spectroscopy), heart rate, and pressure of end-tidal CO2 (PET CO2) were recorded. MCAv was 20-25% above resting levels (68 ± 12 cm/s) during submaximal and maximal exercise intensities, despite PET CO2 being reduced during maximal efforts (down ∼ 0.5-0.8 kPa); thus revealing a different perfusion profile to the inverted-U observed in other exercise modes. The afternoon time trial was 3.4 s faster (95% confidence interval 0.9-5.8 s) and mean power output 3.2% higher (337 vs 347 W; P = 0.04), in conjunction with similar exercise-induced elevations in MCAv (P = 0.60) and reductions in cerebral oxygenation (TOI) (P = 0.12). At the muscle, afternoon trials involved similar oxygen extraction (HHb volume and TOI) albeit from a relatively lower total Hb volume (P < 0.01). In conclusion, rowing performance was better in the afternoon, but not in conjunction with differences in MCAv or exercise-induced differences in cerebral oxygenation.

Short-term heat acclimation is effective and may be enhanced rather than impaired by dehydration.

UNLABELLED: Most heat acclimation data are from regimes longer than 1 week, and acclimation advice is to prevent dehydration. OBJECTIVES: We hypothesized that (i) short-term (5-day) heat acclimation would substantially improve physiological strain and exercise tolerance under heat stress, and (ii) dehydration would provide a thermally independent stimulus for adaptation. METHODS: Nine aerobically fit males heat acclimated using controlled-hyperthermia (rectal temperature 38.5°C) for 90 min on 5 days; once euhydrated (EUH) and once dehydrated (DEH) during acclimation bouts. Exercising heat stress tests (HSTs) were completed before and after acclimations (90-min cycling in Ta 35°C, 60% RH). RESULTS: During acclimation bouts, [aldosterone]plasma rose more across DEH than EUH (95%CI for difference between regimes: 40-411 pg ml(-1); P = 0.03; n = 5) and was positively related to plasma volume expansion (r = 0.65; P = 0.05), which tended to be larger in DEH (CI: -1 to 10%; P = 0.06; n = 9). In HSTs, resting forearm perfusion increased more in DEH (by 5.9 ml 100 tissue ml(-1) min(-1): -11.5 to -1.0; P = 0.04) and end-exercise cardiac frequency fell to a greater extent (by 11 b min(-1): -1 to 22; P = 0.05). Hydration-related effects on other endocrine, cardiovascular, and psychophysical responses to HSTs were unclear. Rectal temperature was unchanged at rest but was 0.3°C lower at end exercise (P < 0.01; interaction: P = 0.52). CONCLUSIONS: Short-term (5-day) heat acclimation induced effective adaptations, some of which were more pronounced after fluid-regulatory strain from permissive dehydration, and not attributable to dehydration effects on body temperature.

Compression garments do not alter cerebrovascular responses to orthostatic stress after mild passive heating.

Whole-body heating increases the likelihood of syncope, whereas utilizing lower-body compression garments may reduce syncope risk. We hypothesized that graded compression garments would reduce the typically observed large postural reductions in arterial blood pressure and middle cerebral artery velocity, in normothermia and especially once passively heat stressed. Fifteen men (age: 27 ± 4 years, aerobic fitness range: 30-75 mL/kg(/) min) completed a supine-to-stand orthostatic challenge for 3 min at normothermia and after passive heating (esophageal temperature, +0.5 °C from baseline) on two occasions (> 7 days): once wearing commercially available compression trousers and once wearing low-compression placebo trousers (randomized order). Blood flow velocity in the middle cerebral artery (transcranial Doppler), mean arterial blood pressure (mean BP: Finometer) and end-tidal carbon dioxide pressure were measured continuously. During normothermia, compression, garments did not alter the magnitude of the postural changes in mean BP or middle cerebral artery velocity. After passive heating, although the magnitudes of these changes were exaggerated, they were not significantly affected by compression garments. Compression garments did not attenuate the initial or sustained orthostatic hypotension associated with posture change, either during normothermia or following passive heat stress.

Influence of sympathoexcitation at high altitude on cerebrovascular function and ventilatory control in humans.

We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3-10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and ß-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco(2) and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated (P < 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02-0.07 Hz) increased, and phase lead was reduced (all P < 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (-40 ± 23%; P < 0.01). In contrast, blockade at HA reduced low-frequency coherence (-26 ± 20%; P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238%; P < 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA (P < 0.01), blockade increased it comparably at SL and HA (∼43-68%; P < 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced (P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.

Effects of aerobic fitness on hypohydration-induced physiological strain and exercise impairment.

AIM: Hypohydration exacerbates cardiovascular and thermal strain and can impair exercise capacity in temperate and warm conditions. Yet, athletes often dehydrate in exercise, are hypervolaemic and have less cardiovascular sensitivity to acute hypervolaemia. We tested the hypothesis that trained individuals have less cardiovascular, thermoregulatory and performance affect of hypohydration during exercise. METHODS: After familiarization, six trained [VO(2 peak) = 64 (SD 8) mL kg(-1) min(-1)] and six untrained [O(2 peak) = 45 (4) mL kg(-1) min(-1)] males cycled 40 min at 70%O(2 peak) while euhydrated or hypohydrated by 1.5-2.0% body mass (crossover design), before a 40-min work trial with euhydration or ad libitum drinking (in Hypohydration trial), in temperate conditions (24.3 degrees C, RH 50%, v(a) = 4.5 m s(-1)). Baseline hydration was by complete or partial rehydration from exercise+heat stress the previous evening. RESULTS: During constant workload, heart rate and its drift were increased in Hypohydration compared with Euhydration for Untrained [drift: 33 (11) vs. 24 beats min(-1) h(-1) (10), 95% CI 5-11] but not Trained [14 (3) vs. 13 beats min(-1) h(-1) (3), CI -2 to 3; P = 0.01 vs. Untrained]. Similarly, rectal temperature drift was faster in Hypohydration for Untrained only [by 0.57 degrees C h(-1) (0.25); P = 0.03 vs. Trained], concomitant with their reduced sweat rate (P = 0.05) and its relation to plasma osmolality (P = 0.03). Performance power tended to be reduced for Untrained (-13%, CI -35 to 2) and Trained (-7%, CI: -16 to 1), without an effect of fitness (P = 0.38). CONCLUSION: Mild hypohydration exacerbated cardiovascular and thermoregulatory strain and tended to impair endurance performance, but aerobic fitness attenuated the physiological effects.

The effects of ageing and passive heating on cardiorespiratory and cerebrovascular responses to orthostatic stress in humans.

We tested the hypothesis that older adults, relative to younger adults, would be more prone to critical reductions in cerebral blood flow and oxygenation upon standing during passive heat stress. Six older (70+/-4 years, mean+/-s.d.) and six younger males (29+/-4 years) were heated (oesophageal temperature raised 0.5 degrees C) in a water-perfused suit. Blood flow velocity in the middle cerebral artery (MCAv), cerebral oxygenation, mean arterial pressure (MAP) and end-tidal partial pressure of carbon dioxide (PET,CO2) were measured continuously before and during 3 min standing in each thermal state. At supine normothermic baseline, MCAv was 47% lower in older participants (P<0.001), whilst MAP and cerebral oxygenation were similar between groups (P>0.05). Heating lowered the supine MAP more in younger adults, and elevated heart rate only in this group. Upon initial standing in normothermia, older participants had a greater drop in MCAv (P<0.05 versus young), a lesser drop in MAP (approximately 24 and approximately 42% in older and younger participants, respectively), but slower recovery of MAP (27.3+/-6.8 versus 18.6+/-4.7 s, mean+/-s.d., P=0.004); heating did not exacerbate any postural responses in either age group. During the last minute of standing, MCAv and PET,CO2 were lower in older participants, though age differences were not evident in cerebral oxygenation (normothermic or heated). Thus, independent of heat stress, in addition to lower resting MCAv, there are further age-related reductions in MCAv and slower corrections of MAP following standing. However, these asymptomatic changes seem to represent a physiologically acceptable insult which can be well tolerated in otherwise healthy older participants even during heat stress.

The effect of multidirectional mechanical vibration on peripheral circulation of humans.

The physiological response of humans to vibration has intrigued researchers for some time, and recently in relation to its potential as a non-pharmacological means to improve peripheral blood flow. A new vibration device [Arapal Technologies Ltd (ATL), Christchurch, New Zealand] for pain relief that purportedly delivers multidirectional vibration waveforms, has been developed. The aim of the study was to quantify the effect of 30 min of mechanical vibration (60 Hz) using two ATL massage devices concurrently upon local peripheral blood flow in healthy humans. On the basis of past work it was expected that acute exposure of the body to the vibratory stimulus would increase local peripheral blood flow. In a randomized cross-over design, mean blood flow (MBF) to the calf was measured using venous occlusion plethysmography before, during 3 min and after 30 min exposure to the vibratory devices or placebo (non-vibratory) devices. Statistical analysis revealed no consistent differences between conditions and considerable individual variability. The MBF increase tended to be higher in the vibration condition than the placebo condition (P=0.16, 95% likely range=-14.4% to 82.2%), the mean increase from resting blood flow at the post-test was 26+/-49% in the vibration condition and 12+/-39% in the placebo condition. It took approximately 22 min of exposure to the vibratory stimulus to elicit peak blood flow (18 min with the placebo). Improvements in local blood flow may be beneficial in the therapeutic alleviation of pain or other symptoms resulting from acute or chronic musculoskeletal injuries.

Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise.

AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 +/- 11 years; cycling Vo(2peak): males 57.4 +/- 5.9, females 48.1 +/- 4.0 mL kg(-1) min(-1)). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. RESULTS: After the race fat mass was decreased by 1.6 +/- 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 +/- 0.06 and 0.93 +/- 0.03 before, to 0.71 +/- 0.01 and 0.85 +/- 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 +/- 74 to 1407 +/- 118 micromol L(-1); P < 0.01). Muscle glycogen content fell 50% (from 554 +/- 28 to 270 +/- 25 nmol kg(-1) d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 +/- 5 to 22 +/- 3 mmol kg(-1) d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor gamma co-activator-1beta mRNA tended to be lower (P = 0.06). CONCLUSION: Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes.

Ventilatory changes in heat-stressed humans with spinal-cord injury.

STUDY DESIGN: Single trial using matched subjects under tightly-controlled experimental conditions. OBJECTIVE: Humans with spinal-cord injury have a reduced ability to dissipate heat. The current project examined the possibility that, in such people, an elevated ventilatory response (panting) may act as a supplementary avenue for heat loss. SETTING: Australia, New South Wales. METHODS: Breathing frequency was measured during a resting heat exposure (

Effect of glycerol-induced hyperhydration on thermoregulation and metabolism during exercise in heat.

This study examined the effect of glycerol ingestion on fluid homeostasis, thermoregulation, and metabolism during rest and exercise. Six endurance-trained men ingested either 1 g glycerol in 20 ml H2O x kg(-1) body weight (bw) (GLY) or 20 ml H2O x kg(-1) bw (CON) in a randomized double-blind fashion, 120 min prior to undertaking 90 min of steady state cycle exercise (SS) at 98% of lactate threshold in dry heat (35 degrees C, 30% RH), with ingestion of CHO-electrolyte beverage (6% CHO) at 15-min intervals. A 15-min cycle, where performance was quantified in kJ, followed (PC). Pre-exercise urine volume was lower in GLY than CON (1119 +/- 97 vs. 1503 +/- 146 ml x 120 min(-1); p < .05). Heart rate was lower (p < .05) throughout SS in GLY, while forearm blood flow was higher (17.1 +/- 1.5 vs. 13.7 +/- 3.0 ml x 100 g tissue x min(-1); p < .05) and rectal temperature lower (38.7 +/- 0.1 vs. 39.1 +/- 0.1 degrees C; p < .05) in GLY late in SS. Despite these changes, skin and muscle temperatures and circulating catecholamines were not different between trials. Accordingly, no differences were observed in muscle glycogenolysis, lactate accumulation, adenine nucleotide, and phosphocreatine degradation or inosine 5'-monophosphate accumulation when comparing GLY with CON. Of note, the work performed during PC was 5% greater in GLY (252 +/- 10 vs. 240 +/- 9 kJ; p < .05). These results demonstrate that glycerol, when ingested with a bolus of water 2 hours prior to exercise, results in fluid retention, which is capable of reducing cardiovascular strain and enhancing thermoregulation. Furthermore, this practice increases exercise performance in the heat by mechanisms other than alterations in muscle metabolism.

The influence of whole-body vs. torso pre-cooling on physiological strain and performance of high-intensity exercise in the heat.

Little research has been reported examining the effects of pre-cooling on high-intensity exercise performance, particularly when combined with strategies to keep the working muscle warm. This study used nine active males to determine the effects of pre-cooling the torso and thighs (LC), pre-cooling the torso (ice-vest in 3 degrees C air) while keeping the thighs warm (LW), or no cooling (CON: 31 degrees C air), on physiological strain and high-intensity (45-s) exercise performance (33 degrees C, 60% rh). Furthermore, we sought to determine whether performance after pre-cooling was influenced by a short exercise warm-up. The 45-s test was performed at different (P<0.05) mean core temperature [(rectal+oesophageal)/2] [CON: 37.3+/-0.3 (S.D.), LW: 37.1+/-0.3, LC: 36.8+/-0.4 degrees C] and mean skin temperature (CON: 34.6+/-0.6, LW: 29.0+/-1.0, LC: 27.2+/-1.2 degrees C) between all conditions. Forearm blood flow prior to exercise was also lower in LC (3.1+/-2.0 ml 100 ml tissue(-1) x min(-1)) than CON (8.2+/-2.5, P=0.01) but not LW (4.3+/-2.6, P=0.46). After an exercise warm-up, muscle temperature (Tm) was not significantly different between conditions (CON: 37.3+/-1.5, LW: 37.3+/-1.2, LC: 36.6+/-0.7 degrees C, P=0.16) but when warm-up was excluded, T(m) was lower in LC (34.5+/-1.9 degrees C, P=0.02) than in CON (37.3+/-1.0) and LW (37.1+/-0.9). Even when a warm-up was performed, torso+thigh pre-cooling decreased both peak (-3.4+/-3.8%, P=0.04) and mean power output (-4.1+/-3.8%, P=0.01) relative to the control, but this effect was markedly larger when warm-up was excluded (peak power -7.7+/-2.5%, P=0.01; mean power -7.6+/-1.2%, P=0.01). Torso-only pre-cooling did not reduce peak or mean power, either with or without warm-up. These data indicate that pre-cooling does not improve 45-s high-intensity exercise performance, and can impair performance if the working muscles are cooled. A short exercise warm-up largely removes any detrimental effects of a cold muscle on performance by increasing Tm.

Effect of pre-cooling, with and without thigh cooling, on strain and endurance exercise performance in the heat.

Body cooling before exercise (i.e. pre-cooling) reduces physiological strain in humans during endurance exercise in temperate and warm environments, usually improving performance. This study examined the effectiveness of pre-cooling humans by ice-vest and cold (3 degrees C) air, with (LC) and without (LW) leg cooling, in reducing heat strain and improving endurance performance in the heat (35 degrees C, 60% RH). Nine habitually-active males completed three trials, involving pre-cooling (LC and LW) or no pre-cooling (CON: 34 degrees C air) before 35-min cycle exercise: 20 min at approximately 65% VO2peak then a 15-min work-performance trial. At exercise onset, mean core (Tc, from oesophagus and rectum) and skin temperatures, forearm blood flow (FBF), heart rate (HR), and ratings of exertion, body temperature and thermal discomfort were lower in LW and LC than CON (P<0.05). They remained lower at 20 min [e.g. Tc: CON 38.4+/-0.2 (+/-S.E.), LW 37.9+/-0.1, and LC 37.8+/-0.1 degrees C; HR: 177+/-3, 163+/-3 and 167+/-3 b.p.m.), except that FBF was equivalent (P=0.10) between CON (15.5+/-1.6) and LW (13.6+/-1.0 ml.100 ml tissue(-1) x min(-1)). Subsequent power output was higher in LW (2.95+/-0.24) and LC (2.91+/-0.25) than in CON (2.52+/-0.28 W kg(-1), P=0.00, N=8), yet final Tc remained lower. Pre-cooling by ice-vest and cold air effectively reduced physiological and psychophysical strain and improved endurance performance in the heat, irrespective of whether thighs were warmed or cooled.