Exercise is a uniquely effective and pluripotent medicine against several noncommunicable disease... more Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduc...
It has been suggested that the suppression of cell-mediated immune phenomena following niridazole... more It has been suggested that the suppression of cell-mediated immune phenomena following niridazole administration is most likely due to a niridazole metabolite rather than the parent drug. This hypothesis was tested using two inbred strains of mice that manifest different rates of microsomal niridazole oxidation and reduction. DBA/2J mice were found to metabolize niridazole at a rate approximately 3-fold greater than C57BI.J6J mice under both aerobic and anaerobic conditions. Nlridazole was found to be more potent with respect to suppression of cutaneous delayed hypersensitivity in the former than in the latter. An immunosuppressive component was isolated from the urine fraction obtained from niridazole-treated rats. This component was found to be chromatographically pure; have a simple UV absorbance spectnJm containing no 360 nm absorbing material characteristic of niridazole; to show no strain difference with respect to potency or efficacy in the ear-swelling assay for cutaneous delayed hypersensitivity; and to be 107 times more potent than niridazole with respect to the suppression of cutaneous delayed hypersensitivity.
Hypercapnia impairs cerebrovascular control during rapid changes in blood pressure (BP); however,... more Hypercapnia impairs cerebrovascular control during rapid changes in blood pressure (BP); however, data concerning the effect of hypercapnia on steady state, nonpharmacological increases in BP is scarce. We recruited fifteen healthy volunteers (mean AE SD: age, 28 AE 6 years; body mass, 77 AE 12 kg) to assess the effect of hypercapnia on cerebrovascular control during steadystate elevations in mean arterial BP (MAP), induced via lower body positive pressure (LBPP). Following 20 min of supine rest, participants completed 5 min of eucapnic 20 and 40 mm Hg LBPP (order randomized) followed by 5 min of hypercapnia (5% CO 2 in air) with and without LBPP (order randomized), and each stage was separated by ≥5 min to allow for recovery. Middle cerebral artery blood velocity (MCAv), BP, partial pressure of endtidal carbon dioxide (P ET CO 2) and heart rate were recorded and presented as the change from the preceding baseline. No difference in MCAv was apparent between eupcapnic baseline and LBPPs (grouped mean 65 AE 11 cmÁs À1 , all P > 0.05), despite the increased MAP with LBPP (D6 AE 5 and D8 AE 3 mm Hg for 20 and 40 mm Hg, respectively, both P < 0.001 vs. baseline). Conversely, MCAv during the hypercapnic +40 mm Hg stage (D31 AE 13 cmÁs À1) was greater than hypercapnia alone (D25 AE 11 cmÁs À1 , P = 0.026), due to an increased MAP (D14 AE 7 mm Hg, P < 0.001 vs. hypercapnia alone and P = 0.026 vs. hypercapnia +20 mm Hg). As cardiac output and P ET CO 2 were similar across all hypercapnic stages (all P > 0.05), our findings indicate that hypercapnia impairs static autoregulation, such that higher blood pressures are translated into the cerebral circulation.
We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle m... more We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle microvascular perfusion in health and disease. Response to a post-occlusive reactive hyperaemia test was repeated on two occasions .48 h apart in healthy young (28 ± 7 y) and elderly controls (70 ± 5 y), and in peripheral arterial disease patients (PAD, 69 ± 7 y; n 5 10, 9 and 8 respectively). Overall, within-individual reliability was poor (coefficient of variation [CV] range: 15-87%); the most reliable parameter was time to peak (TTP, 15-48% CV). Nevertheless, TTP was twice as long in elderly controls and PAD compared to young (19.3 ± 10.4 and 22.0 ± 8.6 vs. 8.9 ± 6.2 s respectively; p , 0.01), and area under the curve for contrast intensity post-occlusion (a reflection of blood volume) was 50% lower in elderly controls (p , 0.01 versus PAD and young). Thus, CEUS assessment of muscle perfusion during reactive hyperaemia demonstrated poor reliability, yet still distinguished differences between PAD patients, elderly and young controls.
Aims/hypothesis The aim of this study was to investigate whether small doses of intense exercise ... more Aims/hypothesis The aim of this study was to investigate whether small doses of intense exercise before each main meal ('exercise snacks') would result in better blood glucose control than a single bout of prolonged, continuous, moderateintensity exercise in individuals with insulin resistance. Methods Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HR max ]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6×1 min intense (90% HR max) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6×1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions. Results ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4±1.5 mmol/l, p=0.02) but not lunch (0.4±1.0 mmol/l, p=0.22), and was more effective than CONT following dinner (0.7±1.5 mmol/l below CONT; p=0.04). ES also reduced 24 h mean glucose concentration by 0.7±0.6 mmol/l (p=0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6±0.4 mmol/l vs CONT, relative to their baselines; p=0.01). CES was just as effective as ES (p>0.05 for all glycaemic variables) at improving glycaemic control. Conclusions/interpretation Dosing exercise as brief, intense 'exercise snacks' before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.
Scandinavian Journal of Medicine & Science in Sports, 2014
The purpose of this study was to characterize cerebrovascular responses to rowing exercise, inves... more 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 (PETCO2) were recorded. MCAv was 20-25% above resting levels (68 ± 12 cm/s) during submaximal and maximal exercise intensities, despite PETCO2 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.
An altered acid-base balance following ascent to high altitude has been well established. Such ch... more An altered acid-base balance following ascent to high altitude has been well established. Such changes in pH buffering could potentially account for the observed increase in ventilatory CO 2 sensitivity at high altitude. Likewise, if [H + ] is the main determinant of cerebrovascular tone, then an alteration in pH buffering may also enhance the cerebral blood flow (CBF) responsiveness to CO 2 (termed cerebrovascular CO 2 reactivity). However, the effect altered acid-base balance associated with high altitude ascent on cerebrovascular and ventilatory responsiveness to CO 2 remains unclear. We measured ventilation (V E), middle cerebral artery velocity (MCAv; index of CBF) and arterial blood gases at sea level and following ascent to 5050 m in 17 healthy participants during modified hyperoxic rebreathing. At 5050 m, restingV E , MCAv and pH were higher (P < 0.01), while bicarbonate concentration and partial pressures of arterial O 2 and CO 2 were lower (P < 0.01) compared to sea level. Ascent to 5050 m also increased the hypercapnic MCAv CO 2 reactivity (2.9 ± 1.1 vs. 4.8 ± 1.4% mmHg −1 ; P < 0.01) andV E CO 2 sensitivity (3.6 ± 2.3 vs. 5.1 ± 1.7 l min −1 mmHg −1 ; P < 0.01). Likewise, the hypocapnic MCAv CO 2 reactivity was increased at 5050 m (4.2 ± 1.0 vs. 2.0 ± 0.6% mmHg −1 ; P < 0.01). The hypercapnic MCAv CO 2 reactivity correlated with resting pH at high altitude (R 2 = 0.4; P < 0.01) while the central chemoreflex threshold correlated with bicarbonate concentration (R 2 = 0.7; P < 0.01). These findings indicate that (1) ascent to high altitude increases the ventilatory CO 2 sensitivity and elevates the cerebrovascular responsiveness to hypercapnia and hypocapnia, and (2) alterations in cerebrovascular CO 2 reactivity and central chemoreflex may be partly attributed to an acid-base balance associated with high altitude ascent. Collectively, our findings provide new insights into the influence of high altitude on cerebrovascular function and highlight the potential role of alterations in acid-base balance in the regulation in CBF and ventilatory control.
National Research Center on the Gifted and Talented, 2004
ED505476 - Evaluation, Placement, and Progression: Three Sites of Concern for Student Achievement... more ED505476 - Evaluation, Placement, and Progression: Three Sites of Concern for Student Achievement. Research Monograph Series. RM04192.
Objective.-Exercise stress, immune status, and mood are interrelated. The stress of adventure rac... more Objective.-Exercise stress, immune status, and mood are interrelated. The stress of adventure racing is unique; exercise is very prolonged and competitive, with severe sleep deprivation and sustained cognitive demands, usually in arduous terrain and environmental conditions. The purpose of this prospective, descriptive study was to identify mood changes along with symptoms of illness and injury during and in the weeks following an international-level adventure race. Methods.-Mood, sleep, injury, and illness data were collected using questionnaires before, during, and for 2 weeks following New Zealand's Southern Traverse Adventure Race in November 2003. Results.-Mood was variable between athletes, but peaks of altered mood subscores were evident (P Ͻ .05) during the first 24 hours of racing, around race completion, and, as was hypothesized, 3 days after racing. Altered mood subscores resolved within 2 weeks. Symptoms of upper respiratory illness were most common immediately before (25/60, 42%) and after (28/49, 57%) racing, and largely resolved over the 2-week follow-up (5/27, 19%). Skin wounds and infections were common (43/49, 88%) immediately after the race but settled quickly. Pain was universal (100%), and musculoskeletal injury was common (38/48, 79%). Gastrointestinal complaints were common at the finish (8/49, 16%) and during the next 5 days but settled more quickly than upper respiratory symptoms. Conclusions.-Adventure racing of approximately 100 hours causes significant symptomatic injury and illness and mood state disruption, which generally resolve within a fortnight following racing. Disrupted mood and symptoms of illness and injury indicate athlete susceptibility to overreaching or overtraining without sufficient recovery.
The effect of acute arterial baroreflex dysfunction on cerebral autoregulation (CA) in otherwise ... more The effect of acute arterial baroreflex dysfunction on cerebral autoregulation (CA) in otherwise healthy humans is unknown. We identified dynamic CA with and without arterial baroreflex-mediated tachycardia and consequent changes in cardiac output during acute hypotension whilst continuously monitoring changes in middle cerebral artery mean blood velocity (MCA V mean). Acute hypotension was induced in nine healthy subjects (mean ± s.d.; 26 ± 3 years) by releasing bilateral thigh cuffs after 6 min of supra-systolic resting ischaemia. Hypotension was induced before and after sympathetic blockade (β-1 receptors), and combined sympathetic-cholinergic blockade. That sequential bolus injections of sodium nitroprusside (50 μg), followed 60 s later by phenylephrine hydrochloride (50 μg), elicited < 5 beats min −1 change in heart rate was verified to confirm that full cardiac autonomic blockade was achieved. Thigh cuff release elicited a transient drop in mean arterial pressure and resultant tachycardia. This tachycardic response was diminished in full cardiac blockade (vs. control, P = 0.029; vs. β-1 adrenergic blockade, P = 0.031). Dynamic CA was also attenuated in the full blockade condition compared to both control (P = 0.028) and β-1 adrenergic blockade conditions (P = 0.015), and was related with the attenuated tachycardia response (P = 0.015). These data indicate an important role of the cardiac baroreflex in dynamic CA.
Loop gain is an engineering term that predicts the stability of a feedback control system, such a... more Loop gain is an engineering term that predicts the stability of a feedback control system, such as the control of breathing. Based on earlier studies at lower altitudes, it was hypothesized that acclimatization to high altitude would lead to a reduction in loop gain and thus central sleep apnoea (CSA) severity. This study used exposure to very high altitude to induce CSA in healthy subjects to investigate the effect of partial acclimatization on loop gain and CSA severity. Measurements were made on 12 subjects (age 30 ± 10 years, body mass index 22.8 ± 1.9, eight males, four females) at an altitude of 5050 m over a 2-week period upon initial arrival (days 2-4) and following partial acclimatization (days 12-14). Sleep was studied by full polysomnography, and resting arterial blood gases were measured. Loop gain was measured by the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;duty cycle&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; method (duration of hyperpnoea/cycle length). Partial acclimatization to high-altitude exposure was associated with both an increase in loop gain (duty cycle fell from 0.60 ± 0.05 to 0.55 ± 0.06 (P = 0.03)) and severity of CSA (apnoea-hypopnoea index increased from 76.8 ± 48.8 to 115.9 ± 20.2 (P = 0.01)), while partial arterial carbon dioxide concentration fell from 29 ± 3 to 26 ± 2 (P = 0.01). Contrary to the results at lower altitudes, at high-altitude loop gain and severity of CSA increased.
In this study, we examined the effect of 96-125 h of competitive exercise on cognitive and physic... more In this study, we examined the effect of 96-125 h of competitive exercise on cognitive and physical performance. Cognitive performance was assessed using the Stroop test (n = 9) before, during, and after the 2003 Southern Traverse adventure race. Strength (MVC) and strength endurance (time to failure at 70% current MVC) of the knee extensor and elbow flexor muscles were assessed before and after racing. Changes in vertical jump (n = 24) and 30-s Wingate performance (n = 27) were assessed in a different group of athletes. Complex response times were affected by the race (16% slower), although not significantly so (P = 0.18), and were dependent on exercise intensity (less so at 50% peak power output after racing). Reduction of strength (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) of the legs (17%) and arms (11%) was equivalent (P = 0.17). Reductions in strength endurance were inconsistent (legs 18%, P = 0.09; arms 13%, P = 0.40), but were equivalent between limbs (P = 0.80). Similar reductions were observed in jump height (-8 +/- 9%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and Wingate peak power (-7 +/- 15%, P = 0.04), mean power (-7 +/- 11%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), and end power (-10 +/- 11%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). We concluded that: moderate-intensity exercise may help complex decision making during sustained stress; functional performance was modestly impacted, and the upper and lower limbs were affected similarly despite being used disproportionately.
Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, ∼0630),... more Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, ∼0630), during (T2, ∼1640; T3, ∼0045; T4, ∼0630), and 48-h afterwards (T5, ∼0650). Participants cycled and ran/trekked continuously between test sessions. A 24-h sedentary control trial was undertaken in crossover order. Within testing sessions, participants lay supine and then stood for 6 min, while heart rate variability (spectral analysis of ECG), middle cerebral artery perfusion velocity (MCAv), mean arterial pressure (MAP; Finometer), and end-tidal Pco2 (PetCO2) were measured, and venous blood was sampled for cardiac troponin I. During the exercise trial: 1) two, six, and four participants were orthostatically intolerant at T2, T3, and T4, respectively; 2) changes in heart rate variability were only observed at T2; 3) supine MAP (baseline = 81 ± 6 mmHg) was lower ( P < 0.05) by 14% at T3 and 8% at T4, whereas standing MAP (75 ± 7 mmHg) was lower by 16% at T2, 37% at T3, and 15% at T4; 4...
The functional relationship between dynamic cerebral autoregulation (CA) and arterial baroreflex ... more The functional relationship between dynamic cerebral autoregulation (CA) and arterial baroreflex sensitivity (BRS) in humans is unknown. Given that adequate cerebral perfusion during normal physiological challenges requires the integrated control of CA and the arterial baroreflex, we hypothesized that between-individual variability in dynamic CA would be related to BRS in humans. We measured R-R interval, blood pressure, and cerebral blood flow velocity (transcranial Doppler) in 19 volunteers. BRS was estimated with the modified Oxford method (nitroprusside-phenylephrine injections) and spontaneous low-frequency (0.04–0.15) α-index. Dynamic CA was quantified using the rate of regulation (RoR) and autoregulatory index (ARI) derived from the thigh-cuff release technique and transfer function analysis of spontaneous oscillations in blood pressure and mean cerebral blood flow velocity. Results show that RoR and ARI were inversely related to nitroprusside BRS [ R = −0.72, confidence inte...
The cerebrovasculature dilates or constricts in response to acute blood pressure changes to stabi... more The cerebrovasculature dilates or constricts in response to acute blood pressure changes to stabilize cerebral blood flow across a range of blood pressures. It is unclear, however, whether such dynamic cerebral autoregulation (dCA) is equally effective in responding to falling versus rising blood pressure. In this study we applied a pharmacological approach to evaluate dCA gain to transient hypotension and hypertension and compared this method with 2 established indices of dCA that do not explicitly differentiate between dCA efficacy and falling versus rising blood pressure. Middle cerebral arterial velocity and blood pressure recordings were made in 26 healthy volunteers randomized to 2 protocols. In 10 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with dCA gain to transient hypertension induced with intravenous phenylephrine. In 16 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with ...
There are several reports on syncope occurring following standing at high altitude (HA), yet desc... more There are several reports on syncope occurring following standing at high altitude (HA), yet description of the detailed physiological responses to standing at HA are lacking. We examined the hypothesis that appropriate physiological adjustments to upright posture would be compromised at HA (5050 m). Ten healthy volunteers stood up rapidly from supine rest, for 3 min, at sea level and at 5050 m. Beat-to-beat mean arterial blood pressure (MAP, Finometer), middle cerebral artery blood velocity (MCAv, Transcranial Doppler), end-tidal PCO(2) and PO(2), and heart rate (ECG) were recorded continuously. After 14 days at HA, baseline MAP and MCAv were not different to sea level, although HR was elevated. Neither the magnitude of initial (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;15 s) responses to standing, nor the time course of initial recovery differed at HA compared with sea level (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). By 3 min of standing, MAP was restored to supine values both at sea level (-3 +/- 12 mmHg) and HA (4 +/- 10 mmHg), although there was more complete recovery of HR at sea level (+13 +/- 10 b.min(-1), p = 0.02 vs. + 23 +/- 10 b.min(-1), p = 0.01). Reduced MCAv at 3 min was comparable at sea level and altitude (both -16%). These data indicate that initial cardiovascular and cerebrovascular responses to standing are unaltered when partially acclimatized to HA.
Soluble CD40 ligand (sCD40L) is a powerful marker of cardiovascular risk. Exercise is known to de... more Soluble CD40 ligand (sCD40L) is a powerful marker of cardiovascular risk. Exercise is known to decrease cardiovascular risk, but the impact of ultra-endurance exercise on sCD40L responses is unknown. To examine the relationship between ultra-endurance exercise in trained athletes and levels of sCD40L and its natural ligand sCD40. Control-trial, crossover design, exercise intervention study of sCD40L and sCD40 levels. Outdoor exercise and laboratory testing, single centre study, School of Physical Education, University of Otago, New Zealand. Nine trained ultra-endurance athletes. Athletes exercised (cycled and jogged) for 17 of 24 h. Venous blood was sampled at baseline and serially throughout exercise and 24 and 48 h after exercise. The athletes completed a 24 h control trial on a separate occasion, in randomised order. Mean levels of sCD40L and sCD40 during exercise and rest with 95% CIs. sCD40L levels dropped steadily from baseline (median 4128 pg/ml) to a measured nadir at 24 h following exercise (median 1409 pg/ml) (p=0.01). The levels had started to rise again by 48 h after exercise. When measured as a group, sCD40L levels remained constant during a control rest period. sCD40 levels remained constant on both exercise and control days. Ultra-endurance exercise lowers the levels of the cardiovascular risk marker sCD40L in athletes. These results raise the possibility that exercise-induced changes in sCD40L may provide one of the mechanisms by which exercise lowers cardiovascular risk.
AJP: Regulatory, Integrative and Comparative Physiology, 2009
Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for assessing the ro... more Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for assessing the role of cerebrovascular reactivity on ventilatory control. Despite this, the effect of INDO on breathing stability during wakefulness has yet to be examined. Although the effect of reductions in cerebrovascular CO2 reactivity on ventilatory CO2 sensitivity is likely dependent upon the method used, no studies have compared the effect of INDO on steady-state and modified rebreathing estimates of ventilatory CO2 sensitivity. The latter method includes the influence of Pco2 gradients and cerebral perfusion, whereas the former does not. We examined the hypothesis that INDO-induced reduction in cerebrovascular CO2 reactivity would 1) cause unstable breathing in conscious humans and 2) increase ventilatory CO2 sensitivity during the steady-state method but not during rebreathing methods. We measured arterial blood gases, ventilation (V̇e), and middle cerebral artery velocity (MCAv) before and 90 ...
Exercise is a uniquely effective and pluripotent medicine against several noncommunicable disease... more Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduc...
It has been suggested that the suppression of cell-mediated immune phenomena following niridazole... more It has been suggested that the suppression of cell-mediated immune phenomena following niridazole administration is most likely due to a niridazole metabolite rather than the parent drug. This hypothesis was tested using two inbred strains of mice that manifest different rates of microsomal niridazole oxidation and reduction. DBA/2J mice were found to metabolize niridazole at a rate approximately 3-fold greater than C57BI.J6J mice under both aerobic and anaerobic conditions. Nlridazole was found to be more potent with respect to suppression of cutaneous delayed hypersensitivity in the former than in the latter. An immunosuppressive component was isolated from the urine fraction obtained from niridazole-treated rats. This component was found to be chromatographically pure; have a simple UV absorbance spectnJm containing no 360 nm absorbing material characteristic of niridazole; to show no strain difference with respect to potency or efficacy in the ear-swelling assay for cutaneous delayed hypersensitivity; and to be 107 times more potent than niridazole with respect to the suppression of cutaneous delayed hypersensitivity.
Hypercapnia impairs cerebrovascular control during rapid changes in blood pressure (BP); however,... more Hypercapnia impairs cerebrovascular control during rapid changes in blood pressure (BP); however, data concerning the effect of hypercapnia on steady state, nonpharmacological increases in BP is scarce. We recruited fifteen healthy volunteers (mean AE SD: age, 28 AE 6 years; body mass, 77 AE 12 kg) to assess the effect of hypercapnia on cerebrovascular control during steadystate elevations in mean arterial BP (MAP), induced via lower body positive pressure (LBPP). Following 20 min of supine rest, participants completed 5 min of eucapnic 20 and 40 mm Hg LBPP (order randomized) followed by 5 min of hypercapnia (5% CO 2 in air) with and without LBPP (order randomized), and each stage was separated by ≥5 min to allow for recovery. Middle cerebral artery blood velocity (MCAv), BP, partial pressure of endtidal carbon dioxide (P ET CO 2) and heart rate were recorded and presented as the change from the preceding baseline. No difference in MCAv was apparent between eupcapnic baseline and LBPPs (grouped mean 65 AE 11 cmÁs À1 , all P > 0.05), despite the increased MAP with LBPP (D6 AE 5 and D8 AE 3 mm Hg for 20 and 40 mm Hg, respectively, both P < 0.001 vs. baseline). Conversely, MCAv during the hypercapnic +40 mm Hg stage (D31 AE 13 cmÁs À1) was greater than hypercapnia alone (D25 AE 11 cmÁs À1 , P = 0.026), due to an increased MAP (D14 AE 7 mm Hg, P < 0.001 vs. hypercapnia alone and P = 0.026 vs. hypercapnia +20 mm Hg). As cardiac output and P ET CO 2 were similar across all hypercapnic stages (all P > 0.05), our findings indicate that hypercapnia impairs static autoregulation, such that higher blood pressures are translated into the cerebral circulation.
We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle m... more We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle microvascular perfusion in health and disease. Response to a post-occlusive reactive hyperaemia test was repeated on two occasions .48 h apart in healthy young (28 ± 7 y) and elderly controls (70 ± 5 y), and in peripheral arterial disease patients (PAD, 69 ± 7 y; n 5 10, 9 and 8 respectively). Overall, within-individual reliability was poor (coefficient of variation [CV] range: 15-87%); the most reliable parameter was time to peak (TTP, 15-48% CV). Nevertheless, TTP was twice as long in elderly controls and PAD compared to young (19.3 ± 10.4 and 22.0 ± 8.6 vs. 8.9 ± 6.2 s respectively; p , 0.01), and area under the curve for contrast intensity post-occlusion (a reflection of blood volume) was 50% lower in elderly controls (p , 0.01 versus PAD and young). Thus, CEUS assessment of muscle perfusion during reactive hyperaemia demonstrated poor reliability, yet still distinguished differences between PAD patients, elderly and young controls.
Aims/hypothesis The aim of this study was to investigate whether small doses of intense exercise ... more Aims/hypothesis The aim of this study was to investigate whether small doses of intense exercise before each main meal ('exercise snacks') would result in better blood glucose control than a single bout of prolonged, continuous, moderateintensity exercise in individuals with insulin resistance. Methods Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HR max ]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6×1 min intense (90% HR max) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6×1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions. Results ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4±1.5 mmol/l, p=0.02) but not lunch (0.4±1.0 mmol/l, p=0.22), and was more effective than CONT following dinner (0.7±1.5 mmol/l below CONT; p=0.04). ES also reduced 24 h mean glucose concentration by 0.7±0.6 mmol/l (p=0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6±0.4 mmol/l vs CONT, relative to their baselines; p=0.01). CES was just as effective as ES (p>0.05 for all glycaemic variables) at improving glycaemic control. Conclusions/interpretation Dosing exercise as brief, intense 'exercise snacks' before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.
Scandinavian Journal of Medicine & Science in Sports, 2014
The purpose of this study was to characterize cerebrovascular responses to rowing exercise, inves... more 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 (PETCO2) were recorded. MCAv was 20-25% above resting levels (68 ± 12 cm/s) during submaximal and maximal exercise intensities, despite PETCO2 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.
An altered acid-base balance following ascent to high altitude has been well established. Such ch... more An altered acid-base balance following ascent to high altitude has been well established. Such changes in pH buffering could potentially account for the observed increase in ventilatory CO 2 sensitivity at high altitude. Likewise, if [H + ] is the main determinant of cerebrovascular tone, then an alteration in pH buffering may also enhance the cerebral blood flow (CBF) responsiveness to CO 2 (termed cerebrovascular CO 2 reactivity). However, the effect altered acid-base balance associated with high altitude ascent on cerebrovascular and ventilatory responsiveness to CO 2 remains unclear. We measured ventilation (V E), middle cerebral artery velocity (MCAv; index of CBF) and arterial blood gases at sea level and following ascent to 5050 m in 17 healthy participants during modified hyperoxic rebreathing. At 5050 m, restingV E , MCAv and pH were higher (P < 0.01), while bicarbonate concentration and partial pressures of arterial O 2 and CO 2 were lower (P < 0.01) compared to sea level. Ascent to 5050 m also increased the hypercapnic MCAv CO 2 reactivity (2.9 ± 1.1 vs. 4.8 ± 1.4% mmHg −1 ; P < 0.01) andV E CO 2 sensitivity (3.6 ± 2.3 vs. 5.1 ± 1.7 l min −1 mmHg −1 ; P < 0.01). Likewise, the hypocapnic MCAv CO 2 reactivity was increased at 5050 m (4.2 ± 1.0 vs. 2.0 ± 0.6% mmHg −1 ; P < 0.01). The hypercapnic MCAv CO 2 reactivity correlated with resting pH at high altitude (R 2 = 0.4; P < 0.01) while the central chemoreflex threshold correlated with bicarbonate concentration (R 2 = 0.7; P < 0.01). These findings indicate that (1) ascent to high altitude increases the ventilatory CO 2 sensitivity and elevates the cerebrovascular responsiveness to hypercapnia and hypocapnia, and (2) alterations in cerebrovascular CO 2 reactivity and central chemoreflex may be partly attributed to an acid-base balance associated with high altitude ascent. Collectively, our findings provide new insights into the influence of high altitude on cerebrovascular function and highlight the potential role of alterations in acid-base balance in the regulation in CBF and ventilatory control.
National Research Center on the Gifted and Talented, 2004
ED505476 - Evaluation, Placement, and Progression: Three Sites of Concern for Student Achievement... more ED505476 - Evaluation, Placement, and Progression: Three Sites of Concern for Student Achievement. Research Monograph Series. RM04192.
Objective.-Exercise stress, immune status, and mood are interrelated. The stress of adventure rac... more Objective.-Exercise stress, immune status, and mood are interrelated. The stress of adventure racing is unique; exercise is very prolonged and competitive, with severe sleep deprivation and sustained cognitive demands, usually in arduous terrain and environmental conditions. The purpose of this prospective, descriptive study was to identify mood changes along with symptoms of illness and injury during and in the weeks following an international-level adventure race. Methods.-Mood, sleep, injury, and illness data were collected using questionnaires before, during, and for 2 weeks following New Zealand's Southern Traverse Adventure Race in November 2003. Results.-Mood was variable between athletes, but peaks of altered mood subscores were evident (P Ͻ .05) during the first 24 hours of racing, around race completion, and, as was hypothesized, 3 days after racing. Altered mood subscores resolved within 2 weeks. Symptoms of upper respiratory illness were most common immediately before (25/60, 42%) and after (28/49, 57%) racing, and largely resolved over the 2-week follow-up (5/27, 19%). Skin wounds and infections were common (43/49, 88%) immediately after the race but settled quickly. Pain was universal (100%), and musculoskeletal injury was common (38/48, 79%). Gastrointestinal complaints were common at the finish (8/49, 16%) and during the next 5 days but settled more quickly than upper respiratory symptoms. Conclusions.-Adventure racing of approximately 100 hours causes significant symptomatic injury and illness and mood state disruption, which generally resolve within a fortnight following racing. Disrupted mood and symptoms of illness and injury indicate athlete susceptibility to overreaching or overtraining without sufficient recovery.
The effect of acute arterial baroreflex dysfunction on cerebral autoregulation (CA) in otherwise ... more The effect of acute arterial baroreflex dysfunction on cerebral autoregulation (CA) in otherwise healthy humans is unknown. We identified dynamic CA with and without arterial baroreflex-mediated tachycardia and consequent changes in cardiac output during acute hypotension whilst continuously monitoring changes in middle cerebral artery mean blood velocity (MCA V mean). Acute hypotension was induced in nine healthy subjects (mean ± s.d.; 26 ± 3 years) by releasing bilateral thigh cuffs after 6 min of supra-systolic resting ischaemia. Hypotension was induced before and after sympathetic blockade (β-1 receptors), and combined sympathetic-cholinergic blockade. That sequential bolus injections of sodium nitroprusside (50 μg), followed 60 s later by phenylephrine hydrochloride (50 μg), elicited < 5 beats min −1 change in heart rate was verified to confirm that full cardiac autonomic blockade was achieved. Thigh cuff release elicited a transient drop in mean arterial pressure and resultant tachycardia. This tachycardic response was diminished in full cardiac blockade (vs. control, P = 0.029; vs. β-1 adrenergic blockade, P = 0.031). Dynamic CA was also attenuated in the full blockade condition compared to both control (P = 0.028) and β-1 adrenergic blockade conditions (P = 0.015), and was related with the attenuated tachycardia response (P = 0.015). These data indicate an important role of the cardiac baroreflex in dynamic CA.
Loop gain is an engineering term that predicts the stability of a feedback control system, such a... more Loop gain is an engineering term that predicts the stability of a feedback control system, such as the control of breathing. Based on earlier studies at lower altitudes, it was hypothesized that acclimatization to high altitude would lead to a reduction in loop gain and thus central sleep apnoea (CSA) severity. This study used exposure to very high altitude to induce CSA in healthy subjects to investigate the effect of partial acclimatization on loop gain and CSA severity. Measurements were made on 12 subjects (age 30 ± 10 years, body mass index 22.8 ± 1.9, eight males, four females) at an altitude of 5050 m over a 2-week period upon initial arrival (days 2-4) and following partial acclimatization (days 12-14). Sleep was studied by full polysomnography, and resting arterial blood gases were measured. Loop gain was measured by the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;duty cycle&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; method (duration of hyperpnoea/cycle length). Partial acclimatization to high-altitude exposure was associated with both an increase in loop gain (duty cycle fell from 0.60 ± 0.05 to 0.55 ± 0.06 (P = 0.03)) and severity of CSA (apnoea-hypopnoea index increased from 76.8 ± 48.8 to 115.9 ± 20.2 (P = 0.01)), while partial arterial carbon dioxide concentration fell from 29 ± 3 to 26 ± 2 (P = 0.01). Contrary to the results at lower altitudes, at high-altitude loop gain and severity of CSA increased.
In this study, we examined the effect of 96-125 h of competitive exercise on cognitive and physic... more In this study, we examined the effect of 96-125 h of competitive exercise on cognitive and physical performance. Cognitive performance was assessed using the Stroop test (n = 9) before, during, and after the 2003 Southern Traverse adventure race. Strength (MVC) and strength endurance (time to failure at 70% current MVC) of the knee extensor and elbow flexor muscles were assessed before and after racing. Changes in vertical jump (n = 24) and 30-s Wingate performance (n = 27) were assessed in a different group of athletes. Complex response times were affected by the race (16% slower), although not significantly so (P = 0.18), and were dependent on exercise intensity (less so at 50% peak power output after racing). Reduction of strength (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) of the legs (17%) and arms (11%) was equivalent (P = 0.17). Reductions in strength endurance were inconsistent (legs 18%, P = 0.09; arms 13%, P = 0.40), but were equivalent between limbs (P = 0.80). Similar reductions were observed in jump height (-8 +/- 9%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and Wingate peak power (-7 +/- 15%, P = 0.04), mean power (-7 +/- 11%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), and end power (-10 +/- 11%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). We concluded that: moderate-intensity exercise may help complex decision making during sustained stress; functional performance was modestly impacted, and the upper and lower limbs were affected similarly despite being used disproportionately.
Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, ∼0630),... more Nine men completed a 24-h exercise trial, with physiological testing sessions before (T1, ∼0630), during (T2, ∼1640; T3, ∼0045; T4, ∼0630), and 48-h afterwards (T5, ∼0650). Participants cycled and ran/trekked continuously between test sessions. A 24-h sedentary control trial was undertaken in crossover order. Within testing sessions, participants lay supine and then stood for 6 min, while heart rate variability (spectral analysis of ECG), middle cerebral artery perfusion velocity (MCAv), mean arterial pressure (MAP; Finometer), and end-tidal Pco2 (PetCO2) were measured, and venous blood was sampled for cardiac troponin I. During the exercise trial: 1) two, six, and four participants were orthostatically intolerant at T2, T3, and T4, respectively; 2) changes in heart rate variability were only observed at T2; 3) supine MAP (baseline = 81 ± 6 mmHg) was lower ( P < 0.05) by 14% at T3 and 8% at T4, whereas standing MAP (75 ± 7 mmHg) was lower by 16% at T2, 37% at T3, and 15% at T4; 4...
The functional relationship between dynamic cerebral autoregulation (CA) and arterial baroreflex ... more The functional relationship between dynamic cerebral autoregulation (CA) and arterial baroreflex sensitivity (BRS) in humans is unknown. Given that adequate cerebral perfusion during normal physiological challenges requires the integrated control of CA and the arterial baroreflex, we hypothesized that between-individual variability in dynamic CA would be related to BRS in humans. We measured R-R interval, blood pressure, and cerebral blood flow velocity (transcranial Doppler) in 19 volunteers. BRS was estimated with the modified Oxford method (nitroprusside-phenylephrine injections) and spontaneous low-frequency (0.04–0.15) α-index. Dynamic CA was quantified using the rate of regulation (RoR) and autoregulatory index (ARI) derived from the thigh-cuff release technique and transfer function analysis of spontaneous oscillations in blood pressure and mean cerebral blood flow velocity. Results show that RoR and ARI were inversely related to nitroprusside BRS [ R = −0.72, confidence inte...
The cerebrovasculature dilates or constricts in response to acute blood pressure changes to stabi... more The cerebrovasculature dilates or constricts in response to acute blood pressure changes to stabilize cerebral blood flow across a range of blood pressures. It is unclear, however, whether such dynamic cerebral autoregulation (dCA) is equally effective in responding to falling versus rising blood pressure. In this study we applied a pharmacological approach to evaluate dCA gain to transient hypotension and hypertension and compared this method with 2 established indices of dCA that do not explicitly differentiate between dCA efficacy and falling versus rising blood pressure. Middle cerebral arterial velocity and blood pressure recordings were made in 26 healthy volunteers randomized to 2 protocols. In 10 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with dCA gain to transient hypertension induced with intravenous phenylephrine. In 16 subjects, dCA gain to transient hypotension induced with intravenous nitroprusside was compared with ...
There are several reports on syncope occurring following standing at high altitude (HA), yet desc... more There are several reports on syncope occurring following standing at high altitude (HA), yet description of the detailed physiological responses to standing at HA are lacking. We examined the hypothesis that appropriate physiological adjustments to upright posture would be compromised at HA (5050 m). Ten healthy volunteers stood up rapidly from supine rest, for 3 min, at sea level and at 5050 m. Beat-to-beat mean arterial blood pressure (MAP, Finometer), middle cerebral artery blood velocity (MCAv, Transcranial Doppler), end-tidal PCO(2) and PO(2), and heart rate (ECG) were recorded continuously. After 14 days at HA, baseline MAP and MCAv were not different to sea level, although HR was elevated. Neither the magnitude of initial (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;15 s) responses to standing, nor the time course of initial recovery differed at HA compared with sea level (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). By 3 min of standing, MAP was restored to supine values both at sea level (-3 +/- 12 mmHg) and HA (4 +/- 10 mmHg), although there was more complete recovery of HR at sea level (+13 +/- 10 b.min(-1), p = 0.02 vs. + 23 +/- 10 b.min(-1), p = 0.01). Reduced MCAv at 3 min was comparable at sea level and altitude (both -16%). These data indicate that initial cardiovascular and cerebrovascular responses to standing are unaltered when partially acclimatized to HA.
Soluble CD40 ligand (sCD40L) is a powerful marker of cardiovascular risk. Exercise is known to de... more Soluble CD40 ligand (sCD40L) is a powerful marker of cardiovascular risk. Exercise is known to decrease cardiovascular risk, but the impact of ultra-endurance exercise on sCD40L responses is unknown. To examine the relationship between ultra-endurance exercise in trained athletes and levels of sCD40L and its natural ligand sCD40. Control-trial, crossover design, exercise intervention study of sCD40L and sCD40 levels. Outdoor exercise and laboratory testing, single centre study, School of Physical Education, University of Otago, New Zealand. Nine trained ultra-endurance athletes. Athletes exercised (cycled and jogged) for 17 of 24 h. Venous blood was sampled at baseline and serially throughout exercise and 24 and 48 h after exercise. The athletes completed a 24 h control trial on a separate occasion, in randomised order. Mean levels of sCD40L and sCD40 during exercise and rest with 95% CIs. sCD40L levels dropped steadily from baseline (median 4128 pg/ml) to a measured nadir at 24 h following exercise (median 1409 pg/ml) (p=0.01). The levels had started to rise again by 48 h after exercise. When measured as a group, sCD40L levels remained constant during a control rest period. sCD40 levels remained constant on both exercise and control days. Ultra-endurance exercise lowers the levels of the cardiovascular risk marker sCD40L in athletes. These results raise the possibility that exercise-induced changes in sCD40L may provide one of the mechanisms by which exercise lowers cardiovascular risk.
AJP: Regulatory, Integrative and Comparative Physiology, 2009
Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for assessing the ro... more Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for assessing the role of cerebrovascular reactivity on ventilatory control. Despite this, the effect of INDO on breathing stability during wakefulness has yet to be examined. Although the effect of reductions in cerebrovascular CO2 reactivity on ventilatory CO2 sensitivity is likely dependent upon the method used, no studies have compared the effect of INDO on steady-state and modified rebreathing estimates of ventilatory CO2 sensitivity. The latter method includes the influence of Pco2 gradients and cerebral perfusion, whereas the former does not. We examined the hypothesis that INDO-induced reduction in cerebrovascular CO2 reactivity would 1) cause unstable breathing in conscious humans and 2) increase ventilatory CO2 sensitivity during the steady-state method but not during rebreathing methods. We measured arterial blood gases, ventilation (V̇e), and middle cerebral artery velocity (MCAv) before and 90 ...
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