The effects of sildenafil and acetazolamide on breathing efficiency and ventilatory control during hypoxic exercise

The reduced arterial oxygen tension at high altitude impairs the ability to work. Acetazolamide improves arterial oxygen saturation (SaO₂) by increasing ventilation but is associated with an increased work and cost of breathing. Depending on the settings, sildenafil can also increases SaO₂ possibly through a reduction in pulmonary hypertension and interstitial edema, which could improve ventilation–perfusion matching. The objective of this study is to determine the effects of acetazolamide and sildenafil on ventilatory control and breathing efficiency (V _E/VCO₂) during submaximal steady-state hypoxic exercise in healthy individuals. Following 18 h of hypoxic exposure in an altitude tent at an oxygen concentration of 12.5% (simulated altitude of 4,300 m), 15 participants performed 10 min of hypoxic exercise on a stationary bicycle at 40% of their sea level peak oxygen uptake (VO₂) while randomly receiving sildenafil 40 mg (SIL), acetazolamide 125 mg (ACZ) or a placebo (PLA). There was no difference in VO₂ during exercise between conditions while SaO₂ was greater with acetazolamide compared to both placebo and sildenafil. Acetazolamide increased ventilation (PLA 49.0 ± 3.2, SIL 47.7 ± 3.1, ACZ 52.1 ± 3.0 l/min) and reduced end-tidal CO₂ (P _ETCO₂) (PLA 32.1 ± 0.8, SIL 32.8 ± 0.9, ACZ 29.2 ± 0.7 mmHg) compared to placebo and sildenafil. Breathing was less efficient with acetazolamide (increased V _E/VCO₂) in comparison to placebo and sildenafil (PLA 41.5 ± 1.0, SIL 40.4 ± 1.3, ACZ 45.4 ± 1.0) while sildenafil did not change V _E/VCO₂ during hypoxic exercise. In conclusion, acetazolamide increased ventilation and reduced breathing efficiency while sildenafil did not affect breathing efficiency despite a trend toward a blunted ventilatory response, possibly due to a reduction in pulmonary hypertension and/or ventilatory drive, during submaximal hypoxic exercise in healthy individuals.     

Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes: alveolar-capillary membrane conductance in type 1 diabetes

Lung diffusing capacity (DLCO) is influenced by alveolar-capillary membrane conductance (D _M) and pulmonary capillary blood volume (V _C), both of which can be impaired in sedentary type 1 diabetes mellitus (T1DM) subjects due to hyperglycemia. We sought to determine if T1DM, and glycemic control, affected DLNO, DLCO, D _M, V _C and SaO₂ during maximal exercise in aerobically fit T1DM subjects. We recruited 12 T1DM subjects and 18 non-diabetic subjects measuring DLNO, DLCO, D _M, and V _C along with SaO₂ and cardiac output (Q) at peak exercise. The T1DM subjects had significantly lower DLCO/Q and D _M/Q with no difference in Q, DLNO, DLCO, D _M, or V _C (DLCO/Q = 2.1 ± 0.4 vs. 1.7 ± 0.3, D _M/Q = 2.8 ± 0.6 vs. 2.4 ± 0.5, non-diabetic and T1DM, p < 0.05). In addition, when considering all subjects there was a relationship between DLCO/Q and SaO₂ at peak exercise (r = 0.46, p = 0.01). Within the T1DM group, the optimal glycemic control group (HbA1c <7%, n = 6) had higher DLNO, DLCO, and D _M/Q than the poor glycemic control subjects (HbA1c ≥7%, n = 6) at peak exercise (DLCO = 38.3 ± 8.0 vs. 28.5 ± 6.9 ml/min/mmHg, DLNO = 120.3 ± 24.3 vs. 89.1 ± 21.0 ml/min/mmHg, D _M/Q = 3.8 ± 0.8 vs. 2.7 ± 0.2, optimal vs. poor control, p < 0.05). There was a negative correlation between HbA1c with DLCO, D _M and D _M/Q at peak exercise (DLCO: r = −0.70, p = 0.01; D _M: r = −0.70, p = 0.01; D _M/Q: r = −0.68, p = 0.02). These results demonstrate that there is a reduction in lung diffusing capacity in aerobically fit athletes with T1DM at peak exercise, but suggests that maintaining near-normoglycemia potentially averts lung diffusion impairments.     

Right ventricular function with hypoxic exercise: effects of sildenafil

The effect of sildenafil on right ventricular contractility in hypoxic exercise is unknown, whereas reports have shown that sildenafil is associated with a smaller increase in pulmonary vascular resistance and right ventricular systolic pressure (RVSP) with exercise at high altitude. The present study evaluates the changes induced by controlled hypoxia on right ventricular pressure and performance with and without sildenafil administration. Tricuspid annular isovolumic acceleration (IVA) and annular velocities were measured in 14 healthy subjects at rest and after maximal exercise in a cross-over, double blind placebo controlled trial in three situations: normoxia, normobaric hypoxia with, and normobaric hypoxia without the administration of 100 mg sildenafil. RVSP, assessed by Doppler echocardiography, was determined from the peak tricuspid regurgitation pressure gradient. RVSP during rest increased from 26.9 ± 2.3 mmHg in normoxia to 37.8 ± 6.9 mmHg in hypoxia, p < 0.01; sildenafil administration reduced RVSP in hypoxia to 30.5 ± 5.6, p < 0.01. Compared to normoxia at rest, IVA increased similarly with peak exercise in normoxia and hypoxia_sildenafil (by 2.37 and 1.90 m/s², respectively), but the observed increase in IVA during exercise was smaller (0.86 m/s², p < 0.05) in hypoxia_placebo. Right ventricular contractility, as estimated by IVA at peak exercise is increased with the administration of sildenafil as compared to placebo, and is not different from the values seen during exercise in normoxia. This effect seems independent of the effect of sildenafil on RVSP.     

Enhanced cerebral CO2 reactivity during strenuous exercise in man

Light and moderate exercise elevates the regional cerebral blood flow by ~20% as determined by ultrasound Doppler sonography (middle cerebral artery mean flow velocity; MCA V _mean). However, strenuous exercise, especially in the heat, appears to reduce MCA V _mean more than can be accounted for by the reduction in the arterial CO₂ tension (P _aCO₂). This study evaluated whether the apparently large reduction in MCA V _mean at the end of exhaustive exercise relates to an enhanced cerebrovascular CO₂ reactivity. The CO₂ reactivity was evaluated in six young healthy male subjects by the administration of CO₂ as well as by voluntary hypo- and hyperventilation at rest and during exercise with and without hyperthermia. At rest, P _aCO₂ was 5.1±0.2 kPa (mean ± SEM) and MCA V _mean 50.7±3.8 cm s⁻¹ and the relationship between MCA V _mean and P _aCO₂ was linear (double-log slope 1.1±0.1). However, the relationship became curvilinear during exercise (slope 1.8±0.1; P<0.01 vs. rest) and during exercise with hyperthermia (slope 2.3±0.3; P<0.05 vs. control exercise). Accordingly, the cerebral CO₂ reactivity increased from 30.5±2.7% kPa⁻¹ at rest to 61.4±10.1% kPa⁻¹ during exercise with hyperthermia (P<0.05). At exhaustion P _aCO₂ decreased 1.1±0.2 kPa during exercise with hyperthermia, which, with the determined cerebral CO₂ reactivity, accounted for the 28±10% decrease in MCA V _mean. The results suggest that during exercise changes in cerebral blood flow are dominated by the arterial carbon dioxide tension.     

Decreased lung capillary blood volume post-exercise is compensated by increased membrane diffusing capacity

The diffusing capacity of the lung for carbon monoxide (DLCO) decreases to below the pre-exercise value in the hours following a bout of intense exercise. Two mechanisms have been proposed: (1) development of pulmonary oedema and (2) redistribution of central blood volume to peripheral muscles causing a reduction in pulmonary capillary blood volume (V_c). In the present study DLCO, V_c and the membrane diffusing capacity (D_m) were measured in nine healthy females using a rebreathing method, in contrast to the single breath technique employed in previous studies. DLCO, V_c and D_m were measured before and at 1, 2, 3, 16 and 24 h following maximal treadmill exercise. Compared with pre-exercise values, DLCO was depressed by up to 8.9 (3.0)% (P<0.05) for the first 3 h following exercise, but had returned to pre-exercise values by 16 h post-exercise. V_c fell by 21.2 (4.1)% (P<0.05) at 3 h post-exercise, but at the same time D_m increased by 14.7 (9.1)%. It was concluded that: (1) the increase in D_m made it unlikely that the fall in DLCO was due to interstitial oedema and injury to the blood gas barrier; (2) on the other hand, the reduction in DLCO following exercise was consistent with a redistribution of blood away from the lungs; and (3) the trend for D_m and V_c to reciprocate one another indicates a situation in which a fall in V_c nevertheless promotes gas transfer at the respiratory membrane. It is suggested that this effect is brought about by the reorientation of red blood cells within the pulmonary capillaries following exercise.     

Attenuated relationship between cardiac output and oxygen uptake during high-intensity exercise

Aim: Recent findings have challenged the belief that the cardiac output (CO) and oxygen consumption (VO₂) relationship is linear from rest to maximal exercise. The purpose of this study was to determine the CO and stroke volume (SV) response to a range of exercise intensities, 40–100% of VO_2max, during cycling. Methods: Ten well‐trained cyclists performed a series of discontinuous exercise bouts to determine the CO and SV vs. VO₂ responses. Results: The rate of increase in CO, relative to VO₂, during exercise from 40 to 70% of VO_2max was 4.4 ± 1.4 L L^?1. During exercise at 70–100% of VO_2max, the rate of increase in CO was reduced to 2.1 ± 0.9 L L^?1 (P = 0.01). Stroke volume during exercise at 80–100% of VO_2max was reduced by 7% when compared to exercise at 50–70% of VO_2max (134 ± 5 vs. 143 ± 5 mL per beat, P = 0.02). Whole body arterial‐venous O₂ difference increased significantly as intensity increased. Conclusion: The observation that the rate of increase in CO is reduced as exercise intensity increases suggests that cardiovascular performance displays signs of compromised function before maximal VO₂ is reached.     

Combined spiroergometry and 31P–MRS of human calf muscle during high‐intensity exercise

Simultaneous measurements of pulmonary oxygen consumption (VO₂), carbon dioxide exhalation (VCO₂) and phosphorus magnetic resonance spectroscopy (³¹P–MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO₂ and VCO₂ whilst simultaneously performing ³¹P–MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR‐compatible pedal ergometer. The use of a non‐magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO₂ and VCO₂. Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO₂ = 1.05 ± 0.31 L/min; VCO₂ = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τ_{PCr fast} and pH; R² = 0.73, p < 0.005) and global respiration (τ_{PCr fast} and VO₂; R² = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.     

The relation of ventilation to metabolic rate during moderate exercise in man

Summary To characterize more precisely the relationship between ventilation (V _E) and CO₂ output (VCO₂) during incremental exercise, 35 healthy males were studied at rest and during upright cycle ergometry, with the work rate incremented every 4 min up to each subject's anaerobic threshold ( _an). Twenty-one subjects had arterial blood sampled at rest and in the steady state at each work rate to determine the relationship between physiological dead space ventilation (V _D) and VCO₂. At these work rates arterial PCO₂ was regulated at the resting, control value. V _E (BTPS) was linearly related to VCO₂ from rest to _an with a slope of 24.6. However, the regression had a significant positive intercept of 3.2 L·min^–1. This causes the ventilatory equivalent for CO₂ (i.e., V _E/VCO₂) to decrease with increasing work rates. V _D also increased linearly with increasing VCO₂. However, this was consequent to increased breathing frequency as V _D remained constant. Thus, the observed fall in V _E/VCO₂ with increasing work rates is due to the positive intercept but the inherent relationship between V _E and VCO₂, reflected by the linear regression slope, remains unchanged from rest through moderate exercise.This investigation was supported by National Institutes of Health Grant HL-11907     

Cardiac response to exercise in normal-weight and obese, Hispanic men and women: implications for exercise prescription

Aim: The effects of obesity on cardiac function during incremental exercise to peak oxygen consumption (VO_2peak) have not been previously described. The purpose of this study was to compare submaximal and maximal cardiac function during exercise in normal‐weight and obese adults. Methods: Normal‐weight (n = 20; means ± SE: age = 21.9 ± 0.5 years; BMI = 21.8 ± 0.4 kg m^?2) and obese (n = 15; means ± SE: age = 25.1 ± 5.2 years; BMI = 34.1 ± 01.0 kg m^?2) participants were assessed for body composition, VO_2peak and cardiac variables (thoracic bioimpedance analysis) at rest and at heart rates (HR) of 110, 130, 150 and 170 beats min^?1 and maximal HR during incremental cycling exercise to exhaustion. Differences between groups were assessed with mixed‐model ancova with repeated measures. Cardiac variables were statistically indexed for body surface area and resting HR. VO₂ and arteriovenous oxygen difference (a‐vO₂) were statistically indexed for fat‐free mass and resting HR. Results: Significant main effects for group indicated obese participants had higher cardiac output (Q) index and stroke volume (SV) index but lower ejection fraction (EF) and a‐vO₂ index during incremental exercise to exhaustion compared with their normal‐weight peers, despite similar submaximal and maximal VO₂ and absolute power outputs (P < 0.05). Conclusions: Our findings suggest that although Q index and SV index were higher in obese, young adults, EF and a‐vO₂ index were significantly lower when compared to matched, normal‐weight adults.     

No effect of menstrual cycle phase on fuel oxidation during exercise in rowers

The aim of this investigation was to examine the effects of menstrual cycle phase on substrate oxidation and lactate concentration during exercise. Eleven eumenorrheic female rowers (18.4 ± 1.9 years; 172.0 ± 4.0 cm; 67.2 ± 8.4 kg; 27.7 ± 4.8% body fat) completed 1 h rowing ergometer exercise at 70% of maximal oxygen consumption (VO_2max) during two different phases of the menstrual cycle: the follicular phase (FP) and the luteal phase (LP). Resting and exercise measurements of the whole body energy expenditure, oxygen consumption (VO₂), respiratory exchange ratio (RER), substrate oxidation and lactate blood levels were made. Energy expenditure, VO₂ and heart rate during the 1-h exercise were not significantly different (P > 0.05) among menstrual cycle phases. Resting RER and RER during the entire 1 h exercise period were not significantly different among menstrual cycle phases. There was an increase (P < 0.05) in RER in the transition between rest and exercise and a further increase in RER occurred after the first 30 min of exercise at both menstrual cycle phases. Blood lactate concentrations significantly increased in the transition between rest and exercise and remained relatively constant during the whole 1 h of exercise in both menstrual cycle phases. No menstrual cycle phase effect (P > 0.05) was observed for blood lactate concentrations. In conclusion, our results demonstrated no effect of menstrual cycle phase on substrate oxidation and blood lactate concentration during rowing exercise at 70% of VO_2max in athletes. Normally menstruating female rowers should not be concerned about their menstrual cycle phase with regard to substrate oxidation in everyday training.     

Resting mechanomyography before and after resistance exercise

A number of mechanisms have been proposed to explain the elevation in oxygen consumption following exercise. Biochemical processes that return muscle to its pre-exercise state do not account for all of the extra oxygen consumed after exercise (excess post-exercise oxygen consumption, EPOC). Muscle at rest after aerobic exercise produces mechanomyographic (MMG) activity of increased amplitude, compared to the pre-exercise state, which declines exponentially with the same time constant as EPOC. The purpose of this study was to determine how the resting MMG is affected by resistance exercise, and whether any change is related to oxygen consumption (VO₂). Ten young male subjects (22.9 years) performed 30 min of resistance exercise consisting of one set of 10 repetitions at 50% 1-repetition maximum (1-RM) followed by five sets of eight repetitions at 75% of 1-RM for leg press and leg (knee) extension, with 1 min rest between sets. Oxygen consumption was measured by indirect calorimetry, MMG by an accelerometer placed over the rectus femoris, and surface electromyogram (EMG) with electrodes placed distal to the accelerometer. Recordings were made before exercise and for 5.5 h after exercise. MMG activity, expressed as mean absolute acceleration, was significantly elevated after exercise (P = 0.0006), as was EMG activity expressed as root-mean-square voltage (P = 0.03). MMG and VO₂ demonstrated exponential decay after exercise with similar time constants of 7.5 ± 2.2 and 7.2 ± 1.0 min, respectively. We conclude that resting muscle is more mechanically active following resistance exercise and that this may contribute to an elevated VO₂.     

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women

Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO₂), peak exercise capacity (W _peak), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% F_IO₂) and high (HA; ~3,900 m, 12.8% F_IO₂) altitudes. Eleven men and ten women completed two HA W _peak trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W _peak + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO₂ values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W _peak at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.     

The effects of exercise duration on dynamics of respiratory gas exchange,ventilation, and heart rate

This study investigated the effect of exercise duration on the response dynamics of oxygen consumptionVO₂, carbon dioxide outputVCO₂, ventilation V_E), and cardiac frequency (f _c) following stepped changes in exercise intensity, by manipulating the duration of the pretransition exercise period. A group of 11 healthy men performed a stepped exercise intensity cycling protocol on three separate occasions, each consisting of a stepped increase from 55% to 65% peak oxygen consumptionVO_2,peak of 6-min duration, followed by a stepped decrease to 55%VO_2,peak of 10-min duration. This stepped protocol was preceded by either 5, 15, or 60 min of cycling at 55%VO_2,peak. The response times for each variable were calculated at 10% increments between the prestep baselines and poststep plateaux. Following the stepped increase, the response times forVO₂ at the 50%, 60%, 70%, 80%, and 90% relative increments were significantly reduced in the 60-min condition compared to the 15-min condition (P< 0.05); however, the response times forVCO₂ andf _c were not significantly altered across the three conditions. No significant differences were found in the response times forVO₂,VCO₂ andf _c, across the three conditions following the stepped decrease in exercise intensity. It was concluded that the faster response time of aerobic metabolism to a stepped increase in exercise intensity was mediated by increases in active muscle temperature, leading to improved oxygen utilisation.     

Oxygen uptake kinetics during exercise in adults with Down syndrome

Persons with Down syndrome (DS) have diminished submaximal and peak work capacity. This study evaluated the dynamic response of oxygen uptake at onset and recovery (VO₂ kinetics) of constant-load exercise (moderate intensity 45% VO_2peak) in adults with DS. A total of 27 healthy participants aged 18–50 years performed graded treadmill exercise to assess peak VO₂: 14 with DS (9 males and 5 females) and 13 controls without disabilities (9 males and 4 females). Subjects also performed constant-load exercise tests at 45% VO_2peak to determine VO₂ on-transient and VO₂ off-transient responses. Peak VO₂ was lower in participants with DS as compared to controls (DS 30.2 ± 7.1; controls 46.1 ± 9.6 mL kg⁻¹ min⁻¹, P < 0.05). In contrast, at 45% VO_2peak, the time constants for the VO₂ on-transients (DS 34.6 ± 9.1; controls 37.6 ± 9.0 s) and VO₂ off-transients (DS 36.5 ± 12.3; controls 37.7 ± 7.0 s) were not significantly different between the groups. Additionally, there were no differences between on-transient and off-transient time constants in participants with DS or controls. These data demonstrate that the VO₂ kinetics at onset and recovery of moderate intensity exercise is similar between adults with DS and controls. Therefore, the submaximal exercise performance of these individuals is not affected by slowed VO₂ kinetics.     

A comparison of normal versus low dietary carbohydrate intake on substrate oxidation during and after moderate intensity exercise in women

We compared the effects of consuming a 2-day low-carbohydrate (CHO) diet (low-CHO; 20% CHO, 40% protein, 40% fat) versus an isocaloric 2-day moderate-CHO diet (mod-CHO; 55% CHO, 15% protein, 30% fat) on substrate oxidation during and after exercise in ten active, young women. Subjects were 24.9 ± 6.2% body fat with a VO_2max of 68.8 ± 13.8 ml/kg FFM/min. For 2 days prior to exercise, subjects consumed either the mod-CHO or the low-CHO diet and then completed treadmill exercise at 55% of VO_2max until 350 kcal of energy was expended. During exercise and for 2 h post-exercise, expired gases were analyzed to determine oxidation rates for CHO (CHO-OX) and fat (FAT-OX). Significant differences (p < 0.05) were found between diets for CHO-OX and FAT-OX (mg/kg FFM/min) during exercise, 1 h post-ex, and 2 h post-ex. During exercise, FAT-OX was higher (low-CHO 8.7 ± 2.2 vs. mod-CHO 6.2 ± 2.2) and CHO-OX was lower (low-CHO 25.1 ± 5.6 vs. mod-CHO 31.1 ± 6.2) following the low-CHO diet. A similar trend was observed during 1 h post-ex for FAT-OX (low-CHO 2.2 ± 0.5 vs. mod-CHO 1.6 ± 0.5) and CHO-OX (low-CHO 2.5 ± 1.2 vs. mod-CHO 4.1 ± 1.9), as well as 2 h post-ex for FAT-OX (low-CHO vs. 1.9 ± 0.5 mod-CHO 1.7 ± 0.4) and CHO-OX (low-CHO 2.5 ± 0.9 vs. mod-CHO 3.1 ± 1.1). Significant positive correlations were observed between VO_2max and CHO-OX during exercise and post-exercise, as well as significant negative correlations between VO_2max and FAT-OX post-exercise in the low-CHO condition. Waist circumference and FAT-OX exhibited a significant negative correlation during exercise in the low-CHO condition. Dietary macronutrient intake influenced substrate oxidation in active young women during and after moderate intensity exercise.     

Breathing dry or humid air and exercise-induced asthma during swimming

Summary With a view to investigating the aerobic and anaerobic proportions of oxygen supply during different grades of muscular activity in varying thermal stress, studies have been conducted on six young healthy Indians naturally acclimatized to heat. The subjects were given submaximal exercises of 400, 500, and 600 kgm/min (equivalent to 65.40, 81.75, and 98.10 W) for 6 min on a bicycle ergometer in three different simulated conditions, i.e., comfortable, hot humid, and very hot humid. Their O₂ consumption (VO₂), pulmonary ventilation (V _E) and heart rate (HR) were measured during rest and throughout the exercise period (6 min) and for 30 min post exercise. Blood lactate level (LA) was measured during rest and recovery. From these, the total O₂ cost with aerobic and anaerobic proportions were calculated. Results indicated a significant increase in the total O₂ cost for each exercise with increasing thermal stress, along with a significant increase in the anaerobic fraction and a decrease in the aerobic fraction. The increase in anaerobic contribution to the energy supply processes was further confirmed by a significant increase in relative O₂ debt (l/kg) and in blood lactate level at each work load. Thus, a highly significant correlation (P<0.001) was found between O₂ debt contracted and increase in thermal stress. A significant fall in VO₂ max was also observed in hot humid and very hot humid conditions as against comfortable temperature, with no change in HR max and V _E max.     

Cerebral oxygenation is reduced during hyperthermic exercise in humans

Aim: Cerebral mitochondrial oxygen tension (P_mitoO₂) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO₂) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P_mitoO₂ calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO_2max) 63 ± 6 mL kg⁻¹ min⁻¹]. Results: The CBF, CMRO₂ and P_mitoO₂ remained stable during 1 h of moderate cycling (170 ± 11 W, ∼50% of VO_2max, RPE 9–12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), P_mitoO₂ declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO₂ increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19–20; P < 0.05); the RPE correlated inversely with P_mitoO₂ (r² = 0.42, P < 0.05). Conclusion: These data indicate that strenuous exercise in the heat lowers cerebral P_mitoO₂, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation.     

Effect of β-adrenoceptor stimulation on oxygen consumption and triglyceride/fatty acid cycling after exercise

The purpose of this study was to characterize the effects of prolonged β-adrenoceptor stimulation on O₂ uptake and triglyceride/fatty acid (TG/FA) cycling during rest with and without previous exercise. Eight men performed two exercise (90 min cycling at 56 ± 3 (SD)% of maximal O₂ uptake, followed by 4.5 h bed rest) and two rest-control experiments. In one rest and one exercise experiment a bolus dose (5 μg) of the β-adrenoceptor agonist isoprenaline was given immediately after exercise, followed by a continuous infusion (20 ng kg^–1 min^–1), and at the corresponding time in the rest experiment. In the other experiments saline was given instead. The O₂ uptake increased in the post-exercise period both with and without β-stimulation. The total excess post-exercise oxygen consumption (EPOC) was not different between saline (8.1 ± 1.8 (SE) L) and isoprenaline administration (10.8 ± 1.8 L, P = 0.40). Also, the total accumulated increase in O₂ uptake for the 4.5 h period after isoprenaline infusion was not different between the rest (12.5 ± 2.0 L) and the exercise experiments (15.2 ± 1.7 L, P = 0.40). The rate of TG/FA cycling increased after both exercise and isoprenaline treatment, but no interaction effect was found. In conclusion, the increases observed in O₂ uptake and the rate of TG/FA cycling during β-adrenoceptor stimulation were not increased by a previous exercise bout.     

Metabolic consequences of reduced frequency breathing during submaximal exercise at moderate altitude

Summary The intention of this study was to determine the metabolic consequences of reduced frequency breathing (RFB) at total lung capacity (TLC) in competitive cyclists during submaximal exercise at moderate altitude (1520 m; barometric pressure, P _B=84.6 kPa; 635 mm Hg). Nine trained males performed an RFB exercise test (10 breaths · min ^–1) and a normal breathing exercise test at 75–85% of the ventilatory threshold intensity for 6 min on separate days. RFB exercise induced significant (P<0.05) decreases in ventilation (V _E), carbon dioxide production (VCO₂), respiratory exchange ratio. (RER), ventilatory equivalent for O₂ consumption (V _E/VO₂), arterial O₂ saturation and increases in heart rate and venous lactate concentration, while maintaining a similar OZ consumption (VO₂). During recovery from RFB exercise (spontaneous breathing) a significant (P< 0.05) decrease in blood pH was detected along with increases in V _E, VO₂, VCO₂, RER, and venous partial pressure of carbon dioxide. The results indicate that voluntary hypoventilation at TLC, during submaximal cycling exercise at moderate altitude, elicits systemic hypercapnia, arterial hypoxemia, tissue hypoxia and acidosis. These data suggest that RFB exercise at moderate altitude causes an increase in energy production from glycolytic pathways above that which occurs with normal breathing.     

The pattern of breathing during hypoxic exercise

Summary Breathing pattern was studied in six subjects in normoxia (F_IO₂=0.21) and hypoxia (F_IO₂=0.12) at rest and during incremental work-rate exercise. Ventilation (V) as well as mean inspiratory flow (V_T/T_I) increased with exercise intensity and were augmented in the hypoxic environment, whereas the ratio between inspiratory (T_I) and total (T_tot) breath durations increased with exercise intensity but was unaffected by hypoxia. The relationship of tidal volume (V_T) and inspiratory time duration (T_I) showed linear, coinciding ranges for the normoxic and hypoxic conditions up to V_T/T_I values of about 2.5 l · s⁻¹. At higher V_T/T_I values T_I continued to decrease, whereas V_T tended to level off, an effect which was more evident in the hypoxic condition. The results suggest that the hypoxic augmentation of exercise hyperpnea is primarily brought about by an enhancement of central inspiratory drive, the timing component being largely unaffected by the hypoxic environment, and that at low to moderate levels of exercise hyperpnea inspiratory off-switch mechanisms are essentially unaffected by moderate hypoxia.