Cardiopulmonary and cerebrovascular acclimatization in children and adults at 3800 m.

Maturational differences exist in cardiopulmonary and cerebrovascular function at sea-level, but the impact of maturation on acclimatization responses to high altitude is unknown. Ten children (9.8 ± 2.5 years) and 10 adults (34.7 ± 7.1 years) were assessed at sea-level (BL), 3000 m and twice over 4 days at 3800 m (B1, B4). Measurements included minute ventilation ( V ̇ E ${\dot{V}}_{\rm{E}}$ ), end-tidal partial pressures of oxygen ( P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ ) and carbon dioxide, echocardiographic assessment of pulmonary artery systolic pressure (PASP) and stroke volume (SV) and ultrasound assessment of blood flow through the internal carotid and vertebral arteries was performed to calculate global cerebral blood flow (gCBF). At 3000 m, V ̇ E ${\dot{V}}_{\rm{E}}$ was increased from BL by 19.6 ± 19.1% (P = 0.031) in children, but not in adults (P = 0.835); SV was reduced in children (-11 ± 13%, P = 0.020) but not adults (P = 0.827), which was compensated for by a larger increase in heart rate in children (+26 beats min-1 vs. +13 beats min-1 , P = 0.019). Between B1 and B4, adults increased V ̇ E ${\dot{V}}_{\rm{E}}$ by 38.5 ± 34.7% (P = 0.006), while V ̇ E ${\dot{V}}_{\rm{E}}$ did not increase further in children. The rise in PASP was not different between groups; however, ∆PASP from BL was related to ∆ P ETO 2 ${P}_{{\rm{ETO}}_{\rm{2}}}$ in adults (R2  = 0.288, P = 0.022), but not children. At BL, gCBF was 43% higher in children than adults (P = 0.017), and this difference was maintained at high altitude, with a similar pattern and magnitude of change in gCBF between groups (P = 0.845). Despite V ̇ E ${\dot{V}}_{\rm{E}}$ increasing in children but not adults at a lower altitude, the pulmonary vascular and cerebrovascular responses to prolonged hypoxia are similar between children and adults. KEY POINTS: Children have different ventilatory and metabolic requirements from adults, which may present differently in the pulmonary and cerebral vasculature upon ascent to high altitude. Children (ages 7-14) and adults (ages 23-44) were brought from sea level to high altitude (3000 to 3800 m) and changes in ventilation, pulmonary artery systolic pressure (PASP) and cerebral blood flow (CBF) were assessed over 1 week. Significant increases in ventilation and decreases in left ventricle stroke volume were observed at a lower altitude in children than adults. PASP and CBF increased by a similar relative amount between children and adults at 3800 m. These results help us better understand age-related differences in compensatory responses to prolonged hypoxia in children, despite similar changes in pulmonary artery pressure and CBF between children and adults.

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.

Acute hypoxaemia and vascular function in healthy humans.

NEW FINDINGS: What is the central question of this study? Endothelium-dependent flow-mediated dilatation (FMD) is impaired during acute (60 min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)-induced dilatation] is impaired during acute hypoxic exposure. What is the main finding and its importance? A graded impairment in FMD and GTN-induced dilatation was evident during acute (≤60 min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN-induced dilatation. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050 m), and FMD is impaired after acute exposure (<60 min) to normobaric hypoxia equivalent to ∼5050 m (inspired oxygen fraction âˆ¼0.11). Whether GTN-induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30 min of mild (end-tidal PO2 74 ± 2 mmHg) and moderate (end-tidal PO2 50 ± 3 mmHg) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, -1.2 ± 1.1 versus -3.1 ± 1.7%; P = 0.01) and GTN-induced dilatation (-2.1 ± 1.0 versus -4.2 ± 2.0%; P = 0.01); the declines in FMD and GTN-induced dilatation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6 ± 0.9 versus 0.8 ± 0.7%; P ≤ 0.01). After 30 min of normoxic time control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN-induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30 min of supine rest/inactivity.

Elevations in Intra-cranial blood flow velocities following a SCUBA Dive and the Influence of Post-dive Exercise.

The effect that a SCUBA dive has on cerebral blood flow (CBF) at rest and during exercise is poorly understood. We examined the hypothesis that the altered hemodynamic parameters following a SCUBA dive will lead to differential changes in CBF at rest and during exercise. 16 divers completed a field-based study with a single dive at a depth of 18 m sea water with a 47-min bottom time. A follow-up laboratory based study was conducted - 1 week later. Intra-cranial velocities were measured with transcranial Doppler ultrasound (TCD) pre-dive, post-dive at rest and throughout incremental exercise until exhaustion. Following the dive at rest, middle cerebral artery velocity (MCAv) was elevated 15 and 30 min after surfacing (by 3.3±5.8 and 4.0±6.9 cm/s, respectively; p<0.05); posterior cerebral artery velocity (PCAv) was increased at 30 min after surfacing (by 3.0±4.5 cm/s; p<0.05). During exercise following the dive, both MCAv and PCAv increased up to 150W followed by a decrease towards baseline at 180W (p<0.05). We found no difference in CBV during exercise between field and laboratory studies (p<0.05). The novel finding of this study is the transient elevation in resting intra-cranial velocities within 30 min following a SCUBA dive.

Influence of nocturnal and daytime sleep on initial orthostatic hypotension.

PURPOSE: The incidence of vasovagal syncope is more common in the morning. Previous researchers have reported negligible diurnal variation in the physiological responses associated with initial orthostatic hypotension (IOH). Nevertheless, physical activity and sleep prior to morning and afternoon test times have not been controlled and may influence the findings. We designed a semi-constant routine protocol to examine diurnal variation in cardiorespiratory and cerebrovascular responses to active standing. METHODS: At 06:00 and 16:00 hours, nine males (27 ± 9 years) completed an upright-stand protocol. Altimetry-measured sleep durations were 3.3 ± 0.4 and 3.2 ± 0.6 h immediately prior to the morning and afternoon test times. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv), mean arterial blood pressure (MAP), heart rate (HR), and end-tidal carbon dioxide were obtained. Intestinal body temperature and salivary melatonin concentrations were also measured. RESULTS: Compared with the afternoon, resting HR and body temperature were 4 ± 2 beats min(-1) and 0.45 ± 0.2 °C lower, respectively, whereas melatonin concentration was 28.7 ± 3.2 pg ml(-1) higher in the morning (P ≤ 0.02). Although all individuals experienced IOH at both times of the day, the initial decline in MAP during standing was 13 ± 4 mmHg greater in the afternoon (P = 0.01). Nevertheless, the decline in MCAv was comparable at both times of day (mean difference: 2 ± 3 cm s(-1); P = 0.5). CONCLUSION: These findings indicate that a bout of sleep in the afternoon in healthy young individuals results in greater IOH that is compensated for by effective cerebral blood flow regulation.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery.

We examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CDO2) in excess of that required by an increasing cerebral metabolic rate of oxygen ( CM RO2); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20-60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained CDO2 and elevated absolute CM RO2 at HA compared with SL, the relative increase in CM RO2 was similar during 20-80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain CDO2. Despite adequate CDO2 at HA the brain appears to increase non-oxidative metabolism during exercise and recovery.

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.

Regional brain blood flow in man during acute changes in arterial blood gases.

Despite the importance of blood flow on brainstem control of respiratory and autonomic function, little is known about regional cerebral blood flow (CBF) during changes in arterial blood gases.We quantified: (1) anterior and posterior CBF and reactivity through a wide range of steady-state changes in the partial pressures of CO2 (PaCO2) and O2 (PaO2) in arterial blood, and (2) determined if the internal carotid artery (ICA) and vertebral artery (VA) change diameter through the same range.We used near-concurrent vascular ultrasound measures of flow through the ICA and VA, and blood velocity in their downstream arteries (the middle (MCA) and posterior (PCA) cerebral arteries). Part A (n =16) examined iso-oxic changes in PaCO2, consisting of three hypocapnic stages (PaCO2 =∼15, ∼20 and ∼30 mmHg) and four hypercapnic stages (PaCO2 =∼50, ∼55, ∼60 and ∼65 mmHg). In Part B (n =10), during isocapnia, PaO2 was decreased to ∼60, ∼44, and ∼35 mmHg and increased to ∼320 mmHg and ∼430 mmHg. Stages lasted ∼15 min. Intra-arterial pressure was measured continuously; arterial blood gases were sampled at the end of each stage. There were three principal findings. (1) Regional reactivity: the VA reactivity to hypocapnia was larger than the ICA, MCA and PCA; hypercapnic reactivity was similar.With profound hypoxia (35 mmHg) the relative increase in VA flow was 50% greater than the other vessels. (2) Neck vessel diameters: changes in diameter (∼25%) of the ICA was positively related to changes in PaCO2 (R2, 0.63±0.26; P<0.05); VA diameter was unaltered in response to changed PaCO2 but yielded a diameter increase of +9% with severe hypoxia. (3) Intra- vs. extra-cerebral measures: MCA and PCA blood velocities yielded smaller reactivities and estimates of flow than VA and ICA flow. The findings respectively indicate: (1) disparate blood flow regulation to the brainstem and cortex; (2) cerebrovascular resistance is not solely modulated at the level of the arteriolar pial vessels; and (3) transcranial Doppler ultrasound may underestimate measurements of CBF during extreme hypoxia and/or hypercapnia.

Assessment of cerebral autoregulation: the quandary of quantification.

We assessed the convergent validity of commonly applied metrics of cerebral autoregulation (CA) to determine the extent to which the metrics can be used interchangeably. To examine between-subject relationships among low-frequency (LF; 0.07-0.2 Hz) and very-low-frequency (VLF; 0.02-0.07 Hz) transfer function coherence, phase, gain, and normalized gain, we performed retrospective transfer function analysis on spontaneous blood pressure and middle cerebral artery blood velocity recordings from 105 individuals. We characterized the relationships (n = 29) among spontaneous transfer function metrics and the rate of regulation index and autoregulatory index derived from bilateral thigh-cuff deflation tests. In addition, we analyzed data from subjects (n = 29) who underwent a repeated squat-to-stand protocol to determine the relationships between transfer function metrics during forced blood pressure fluctuations. Finally, data from subjects (n = 16) who underwent step changes in end-tidal P(CO2) (P(ET)(CO2) were analyzed to determine whether transfer function metrics could reliably track the modulation of CA within individuals. CA metrics were generally unrelated or showed only weak to moderate correlations. Changes in P(ET)(CO2) were positively related to coherence [LF: ß = 0.0065 arbitrary units (AU)/mmHg and VLF: ß = 0.011 AU/mmHg, both P < 0.01] and inversely related to phase (LF: ß = -0.026 rad/mmHg and VLF: ß = -0.018 rad/mmHg, both P < 0.01) and normalized gain (LF: ß = -0.042%/mmHg(2) and VLF: ß = -0.013%/mmHg(2), both P < 0.01). However, Pet(CO(2)) was positively associated with gain (LF: ß = 0.0070 cm·s(-1)·mmHg(-2), P < 0.05; and VLF: ß = 0.014 cm·s(-1)·mmHg(-2), P < 0.01). Thus, during changes in P(ET)(CO2), LF phase was inversely related to LF gain (ß = -0.29 cm·s(-1)·mmHg(-1)·rad(-1), P < 0.01) but positively related to LF normalized gain (ß = 1.3% mmHg(-1)/rad, P < 0.01). These findings collectively suggest that only select CA metrics can be used interchangeably and that interpretation of these measures should be done cautiously.

Diurnal variation in time to presyncope and associated circulatory changes during a controlled orthostatic challenge.

Epidemiological data indicate that the risk of neurally mediated syncope is substantially higher in the morning. Syncope is precipitated by cerebral hypoperfusion, yet no chronobiological experiment has been undertaken to examine whether the major circulatory factors, which influence perfusion, show diurnal variation during a controlled orthostatic challenge. Therefore, we examined the diurnal variation in orthostatic tolerance and circulatory function measured at baseline and at presyncope. In a repeated-measures experiment, conducted at 0600 and 1600, 17 normotensive volunteers, aged 26 +/- 4 yr (mean +/- SD), rested supine at baseline and then underwent a 60 degrees head-up tilt with 5-min incremental stages of lower body negative pressure until standardized symptoms of presyncope were apparent. Pretest hydration status was similar at both times of day. Continuous beat-to-beat measurements of cerebral blood flow velocity, blood pressure, heart rate, stroke volume, cardiac output, and end-tidal Pco(2) were obtained. At baseline, mean cerebral blood flow velocity was 9 +/- 2 cm/s (15%) lower in the morning than the afternoon (P < 0.0001). The mean time to presyncope was shorter in the morning than in the afternoon (27.2 +/- 10.5 min vs. 33.1 +/- 7.9 min; 95% CI: 0.4 to 11.4 min, P = 0.01). All measurements made at presyncope did not show diurnal variation (P > 0.05), but the changes over time (from baseline to presyncope time) in arterial blood pressure, estimated peripheral vascular resistance, and alpha-index baroreflex sensitivity were greater during the morning tests (P < 0.05). These data indicate that tolerance to an incremental orthostatic challenge is markedly reduced in the morning due to diurnal variations in the time-based decline in blood pressure and the initial cerebral blood flow velocity "reserve" rather than the circulatory status at eventual presyncope. Such information may be used to help identify individuals who are particularly prone to orthostatic intolerance in the morning.

Effect of intermittent hypoxic training on 20 km time trial and 30 s anaerobic performance.

This study aimed to verify whether the "live low, train high" approach is beneficial for endurance and/or anaerobic cycling performance. Sixteen well-trained athletes completed 90 min of endurance training (60-70% of heart rate reserve), followed by two 30-s all-out sprints (Wingate test), daily, for 10 consecutive days. Nine subjects [intermittent hypoxic training (IHT) group] trained with an F(I)O(2) set to produce arterial oxygen saturations of approximately 88-82%, while seven subjects (placebo group) trained while breathing a normal gas mixture (F(I)O(2)=0.21). Four performance tests were conducted at sea level including a familiarization and baseline trial, followed by repeat trials at 2 and 9 days post-intervention. Relative to the placebo group, the mean power during the 30-s Wingate test increased by 3.0% (95% confidence limits, CL +/- 3.5%) 2 days, and 1.7% (+/- 3.8%) 9 days post-IHT. Changes in other performance variables (30 s peak power, 20 km mean power and 20 km oxygen cost) were unclear. During the time trial, the IHT participants' blood lactate concentration, respiratory exchange ratio, and SpO(2), relative to the placebo group, was substantially increased at 2 days post-intervention. The addition of IHT to the normal training program of well-trained athletes produced worthwhile gains in 30 s sprint performance possibly through enhanced glycolysis.

Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function.

We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O(2)) and following 6 h passive exposure to hypoxia (12% O(2)). Blood flow velocity in the middle cerebral artery (MCAv) and mean arterial blood pressure (MAP) were measured for determination of CA following calculation of transfer function analysis and rate of regulation (RoR). Nine subjects developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS-). A more marked increase in the venous concentration of the ascorbate radical (A(*-)), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during hypoxia in AMS+ (P < 0.05 versus AMS-). Despite a general decline in total nitric oxide (NO) in hypoxia (P < 0.05 versus normoxia), the normoxic baseline plasma and red blood cell (RBC) NO metabolite pool was lower in AMS+ with normalization observed during hypoxia (P < 0.05 versus AMS-). CA was selectively impaired in AMS+ as indicated both by an increase in the low-frequency (0.07-0.20 Hz) transfer function gain and decrease in RoR (P < 0.05 versus AMS-). However, there was no evidence for cerebral hyper-perfusion, BBB disruption or neuronal-parenchymal damage as indicated by a lack of change in MCAv, S100beta and neuron-specific enolase. In conclusion, these findings suggest that AMS is associated with altered redox homeostasis and disordered CA independent of barrier disruption.

Respiratory modulation of cardiovagal baroreflex sensitivity.

Emerging evidence has suggested that with minimal prerequisite training, slow deep breathing around 0.10 Hz can acutely enhance cardiovagal baroreflex sensitivity (BRS) in humans. Such reports have led to the speculation that behavioral interventions designed to reduce breathing frequency may serve a therapeutic role in ameliorating depressed baroreflex function in conditions such as chronic heart failure, essential hypertension, and obstructive airway disease. This study sought to test the hypothesis that slow controlled breathing acutely enhances cardiovagal baroreflex function in young healthy volunteers. Distinct from earlier studies, however, baroreflex function was examined (n = 30) using the classical pharmacological modified Oxford method, which enabled the assessment of cardiovagal BRS through experimentally driven baroreceptor stimulation across a wide range of blood pressures. For a comparison against existing evidence, spontaneous cardiovagal BRS was also assessed using the alpha-index and sequence method. Compared with fast breathing (0.25 Hz), slow breathing (0.10 Hz) was associated with an increase in the alpha-index (8.1 +/- 14 ms/mmHg, P < 0.01) and spontaneous up-sequence BRS (10 +/- 11 ms/mmHg, P < 0.01). In contrast, BRS derived from spontaneous down sequences and the modified Oxford method were unaltered by slow breathing. The lack of change in BRS derived from the modified Oxford method challenges the concept that slow breathing acutely augments arterial baroreflex function in otherwise healthy humans. Our results also provide further evidence that spontaneous BRS may not reflect the BRS determined by experimentally driven baroreceptor stimulation.

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.

Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise.

Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2 ); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2(PetO2 ) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇ewas uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇ewas increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15-20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17-29%) were greater compared with poikilocapnic normoxia (∼8-20%) at intensities >40% Wmax(P< 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2.

Physiological and metabolic responses to a hill walk.

The physiological and metabolic demands of hill walking have not been studied systematically in the field despite the potentially deleterious physiological consequences of activity sustained over an entire day. On separate occasions, 13 subjects completed a self-paced hill walk over 12 km, consisting of a range of gradients and terrain typical of a mountainous walk. During the hill walk, continuous measurements of rectal (T(re)) and skin (T(sk)) temperatures and of respiratory gas exchange were made to calculate the total energy expenditure. Blood samples, for the analysis of metabolites and hormones, were taken before breakfast and lunch and immediately after the hill walk. During the first 5 km of the walk (100- to 902-m elevation), T(re) increased (36.9 +/- 0.2 to 38.5 +/- 0.4 degrees C) with a subsequent decrease in mean T(sk) from this time point. T(re) decreased by approximately 1.0 degrees C during a 30-min stop for lunch, and it continued to decrease a further 0.5 degrees C after walking recommenced. The total energy intake from both breakfast and lunch [5.6 +/- 0.7 (SE) MJ] was lower than the energy expended [14.5 +/- 0.5 (SE) MJ; P < 0.001] during the 12-km hill walk. Despite the difference in energy intake and expenditure, blood glucose concentration was maintained. The major source of energy was an enhanced fat oxidation, probably from adipose tissue lipolysis reflected in high plasma nonesterified fatty acid concentrations. The major observations were the varying thermoregulatory responses and the negative energy balance incurred during the hill walk. It is concluded that recreational hill walking can constitute a significant metabolic and thermoregulatory strain on participants.