Regional V˙A/Q˙ ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation

We describe a technique to obtain non-invasively regional pulmonary ventilation–perfusion ratios (V˙_A/Q˙) using single photon emission computed tomography (SPECT) and continuous infusion of ¹³³Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for V˙_A/Q˙ calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean V˙_A/Q˙ for the whole lung of the normal subjects ranged from 0·49 to 0·65, group mean 0·56 ± 0·07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low V˙_A/Q˙ values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of V˙_A/Q˙, as defined by the standard deviation of the individual distribution functions, ranged from 0·12 to 0·19. One of the patients was characterized by a low mean V˙_A/Q˙ of 0·35, and the other patient had a wide dispersion (SD) of V˙_A/Q˙ of 0·37. In the normal subjects, a consistent V˙_A/Q˙ gradient was found only in the ventrodorsal direction. ¹³³Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.     

Ventilatory inefficiency for carbon dioxide during exercise in patients with pulmonary hypertension

The purpose of this study was to analyse the ventilatory efficiency for carbon dioxide (CO₂) in the assessment of exercise tolerance in patients with pulmonary hypertension. Two groups of patients were studied. One group consisted of 37 patients with normal pulmonary artery pressure who underwent surgical closure of a left-to-right shunt. Another group was composed of 10 patients with pulmonary hypertension. Both patient groups were compared with the mean value of an age-matched pool of normal control subjects. Aerobic exercise performance was assessed by determination of the ventilatory threshold. The ventilatory efficiency for CO₂ was assessed by calculating the slope of ventilation over carbon dioxide below the ventilatory threshold. The slope of ventilation vs. carbon dioxide output in patients with pulmonary hypertension (48 ± 12) was steeper than the slope (31·3 ± 7·0) in patients with normal pulmonary artery pressure (P<0·05). Significant correlations (P<0·05) were found between the pulmonary artery pressure and the slope of pulmonary ventilation over carbon dioxide (r = 0·92) and also with the physiological dead space–tidal volume ratio at maximal exercise (r = 0·55). This was associated with a severe reduction in exercise performance in patients with pulmonary hypertension, whereas in patients with normal pulmonary artery pressure it was only slightly below the lower limit of normal. These results demonstrate that patients with pulmonary hypertension have an inefficient ventilatory response to metabolically produced CO₂ during exercise, which severely limits exercise tolerance.     

Pulmonary capillary blood flow by partial CO2 rebreathing: importance of the regularity of the respiratory pattern

The partial CO₂ rebreathing technique has been shown to be a reliable non‐invasive method for measurement of pulmonary capillary blood flow (Q˙_c), but experience with this technique has been limited to controlled mechanical ventilation. In this study, we evaluated this technique during spontaneous and oriented ventilation in nine subjects without known cardiopulmonary disease. Subjects underwent 10 consecutive (Q˙_c) measurements with both spontaneous and oriented ventilation. Breath‐by‐breath gas exchange was measured and (Q˙_c) was calculated from changes in CO₂ elimination and P_ETCO₂, which were achieved by sudden increase of the apparatus deadspace (rebreathing period). An exponential curve was fitted to the P_ETCO₂ values in the rebreathing period in order to estimate P_ETCO₂ at equilibrium. We found that mean (Q˙_c) values were not influenced by the ventilation pattern (P=0·51), but that the intra‐individual variability with oriented ventilation (median=16·0%) was significantly lower than with spontaneous ventilation (median=31·8%, P=0·039). Accordingly, the curve fitting for rebreathing P_ETCO₂ rise failed in 4·4% of measurements with oriented ventilation vs. 18·9% of measurements with spontaneous ventilation (P=0·039). Our results suggest that the performance of the partial CO₂ rebreathing technique is adversely affected by spontaneous ventilation and, consequently, that this method should be reserved for patients with regular respiratory patterns.     

The effect of dietary restriction and menstrual cycle on excess post‐exercise oxygen consumption (EPOC) in young women

The purpose of this study was to evaluate the effect of acute dietary restriction on excess post‐exercise oxygen consumption (EPOC) in young women at two different phases of the menstrual cycle. Five young sedentary women (age 21–22 years) participated in this study. Each subject visited the laboratory eight times for measurement of EPOC. They performed cycle ergometer exercise for 60 min at a work rate corresponding to approximately 70% of V˙O₂max under each four different conditions (i.e. standard diet/follicular phase (SF), standard diet/luteal phase (SL), restricted diet/follicular phase (RF) and restricted diet/luteal phase (RL)). The exercise was performed in the morning and V˙O₂ was measured for the last 15 min of each hour for 7 h after the exercise. As a control, V˙O₂ was also measured with an identical time schedule under the same four conditions but without exercise. EPOC was calculated as the difference of the V˙O₂–time integral for 7 h between the exercise and control trial days in each of the four conditions (i.e. SL, SF, RL and RF). The diet was precisely controlled during 2 days (i.e. the test day and the day preceding it). The standard diet was 1600 kcal day^–1 and the restricted diet was half of the standard diet. A two‐way (dietary and menstrual cycle factors) ANOVA indicated that EPOC was significantly affected only by the dietary factor. The dietary restriction decreased EPOC compared to the standard dietary condition (SF 8·6 ± 2·1, RF 5·3 ± 1·6, SL 8·9 ± 4·8, RL 4·0 ± 1·2 l). These data indicate that for young sedentary women, EPOC is significantly lowered by prior acute dietary restriction but is not influenced by different phases of the menstrual cycle.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

Summary. The effect of dynamic exercise on muscle and blood ammonia (NH₃) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5·2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH₃ at rest and after submaximal exercise was (x?±SE) 0·5±0·1 mmol/kg dry muscle (d.m.) and increased to 4·1 ±0·5 mmol/kg d.m. at fatigue (P<0·001). The total adenine nucleotide (TAN) pool (TAN=ATP+ADP+AMP) did not change after submaximal exercise but decreased significantly at fatigue (P<0·01). The decrease in TAN was similar to the increase in NH₃. Muscle lactate was 3±1 mmol/kg d.m. at rest and increased to 104±5 mmol/kg d.m. at fatigue. Whole blood and plasma NH₃ did not change significantly during submaximal but both increased significantly during maximal exercise (P<0·001). During maximal exercise the leg released 7,120 μmol/min of lactate, whereas only 89 μmol/min of NH₃ were released. NH₃ accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH₃ release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P<0·001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P<0·001), respectively, during exercise. It is concluded that (1) muscle and blood NH₃ levels increase only during strenuous exercise and (2) NH₃ accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

Intensity of Nordic Walking in young females with different peak O2 consumption

The purpose of this cross‐sectional study was to determine the physiological reaction to the different intensity Nordic Walking exercise in young females with different aerobic capacity values. Twenty‐eight 19–24‐year‐old female university students participated in the study. Their peak O₂ consumption (VO₂ peak kg^?1) and individual ventilatory threshold (IVT) were measured using a continuous incremental protocol until volitional exhaustion on treadmill. The subjects were analysed as a whole group (n = 28) and were also divided into three groups based on the measured VO₂ peak kg^?1 (Difference between groups is 1 SD) as follows: 1. >46 ml min^?1 kg^?1 (n = 8), 2. 41–46 ml min^?1 kg^?1 (n = 12) and 3. <41 ml min^?1 kg^?1 (n = 8). The second test consisted of four times 1 km Nordic Walking with increasing speed on the 200 m indoor track, performed as a continuous study (Step 1 – slow walking, Step 2 – usual speed walking, Step 3 – faster speed walking and Step 4 – maximal speed walking). During the walking test expired gas was sampled breath‐by‐breath and heart rate (HR) was recorded continuously. Ratings of perceived exertion (RPE) were asked using the Borg RPE scale separately for every 1 km of the walking test. No significant differences emerged between groups in HR of IVT (172·4 ± 10·3–176·4 ± 4·9 beats min^?1) or maximal HR (190·1 ± 7·3–191·6 ± 7·8 beats min^?1) during the treadmill test. During maximal speed walking the speed (7·4 ± 0·4–7·5 ± 0·6 km h^?1) and O₂ consumption (30·4 ± 3·9–34·0 ± 4·5 ml min^?1 kg^?1) were relatively similar between groups (P > 0·05). However, during maximal speed walking, the O₂ consumption in the second and third groups was similar with the IVT (94·9 ± 17·5% and 99·4 ± 15·5%, respectively) but in the first group it was only 75·5 ± 8·0% from IVT. Mean HR during the maximal speed walking was in the first group 151·6 ± 12·5 beats min^?1, in the second (169·7 ± 10·3 beats min^?1) and the third (173·1 ± 15·8 beats min^?1) groups it was comparable with the calculated IVT level. The Borg RPE was very low in every group (11·9 ± 2·0–14·4 ± 2·3) and the relationship with VO₂and HR was not significant during maximal speed Nordic Walking. In summary, the present study indicated that walking is an acceptable exercise for young females independent of their initial VO₂ peak level. However, females with low initial VO₂ peak can be recommended to exercise with the subjective ‘faster speed walking’. In contrast, females with high initial VO₂ peak should exercise with maximal speed.     

The exercise heart rate profile in master athletes compared to healthy controls

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle‐aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle‐aged athletes and controls. Fifty endurance‐trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom‐limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O₂ uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg^?1 min^?1; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between‐group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle‐aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.     

Day-to-day variation in oxygen consumption and energy expenditure during submaximal treadmill walking in female adolescents

The day-to-day variation in oxygen consumption (V˙O ₂) and energy expenditure (EE) during horizontal treadmill walking was measured using indirect calorimetry in 20 female adolescents (mean age 17·3 years). Two different walking speeds were used: 5 km h^?1 and an individually convenient speed of 3·0 km h^?1 (mean). The two sets of measurements were performed on 2 consecutive days, and great care was taken to minimize possible disturbing factors. The mean V˙O ₂ was 919 ml min^?1 at 5 km h^?1 and 622 ml min^?1 at the individual speed, and the mean values of EE were 4·5 kcal min^?1 and 3·1 kcal min^?1 respectively. The individual day-to-day variation in V˙O ₂ (at 5 km h^?1) was between ?11·7% and +12·6% of the mean V˙O ₂. The coefficient of variation (CV) was 6·4% when values were calculated in ml min^?1 kg^?1. The energy expenditure varied somewhat less between the 2 days (CV = 5·7%). The corresponding value for EE when walking at the individual speed was 7·2%, and the mean day-to day variation in V˙O ₂ was 7·5% (CV). The rate of perceived exertion according to Borg's scale was lower on day 2 (11·9) compared with day 1 (13·0) when walking at 5 km h^?1. There was no difference in heart rate between the 2 days. It is concluded that EE varies somewhat less than V˙O ₂ on successive days, probably because of an interchangeable relationship between breathing gases, depending on which substrate is used for combustion. When using V˙O ₂ and EE for evaluation of physical capacity, the day-to-day variation in the measurements must be taken into consideration.     

Left ventricular response to graded isometric exercise in patients with coronary heart disease

Summary. The effects of graded isometric exercise on left ventricular performance were characterized in 11 male patients (53 ± 2 years) with coronary artery disease (CAD) and in 12 normal subjects (11 male and one female, 36 ± 5 years). The echocardiographic indices of left ventricular function at rest were similar in both groups. Heart rate and blood pressure increased significantly in both groups in response to 40 and 60% of handgrip maximal voluntary contraction (MVC). Left ventricular end-diastolic dimension increased significantly (from 50 ± 1 to 56 ± 1 mm; P < 0·01) with 60% of MVC in CAD group but not in the healthy subjects. The patients with CAD also exhibited significant (P < 0·01) increases in end-systolic dimension (from 34 ± 1 to 40 ± 2 with 40% and to 44 ± 1 mm with 60% MVC). End-diastolic and end-systolic dimensions did not change during isometric exercise in the healthy subjects. Mean velocity of circumferential shortening (mV_CF) increased with 60% MVC in normal subjects. In the CAD group mV_CF decreased significantly (from 1.08 ± 0·06 to 0·86 ± 0·06 with 40% and to 0·74 ± 0·04 d·s^-1 with 60% MVC; P < 0·01). At comparable mean blood pressures, mV_CF was significantly lower in the CAD group than in normal subjects. These results demonstrate that progressive deterioration of left ventricular function during increasing levels of isometric exercise in patients with CAD can be detected with echocardiography.     

Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO₂) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO₂ similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l^?1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l^?1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO₂ (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.     

Effect of exercise training and detraining on gas exchange kinetics in patients with chronic obstructive pulmonary disease

Symptom-limited incremental exercise tests are used to estimate the training effect on patients with chronic obstructive pulmonary disease (COPD). However, there is a need for objective parameters for measurement on submaximal exercise testing. The purpose of this study was to assess the usefulness of measurement of oxygen uptake (V?O₂) kinetics during a constant work rate exercise test of patients with COPD after exercise training. Eleven patients with COPD performed exercise tests before and after cycle ergometer training on 3 days per week for 8 weeks; they then went without training for 5 months and performed the same tests. They performed an incremental exercise test to symptom-limited maximum and a constant work rate exercise test for 6 min on a cycle ergometer. The time constant of V?O₂ during the onset of constant work rate exercise was significantly decreased (from 63·5±7·8 s to 53·2±8·0 s) after exercise training (P=0·021), but was significantly increased (to 73·4±14·9 s) after 5 months without training (P=0·001). The oxygen pulse at steady state during constant work rate exercise testing was significantly increased after exercise training but decreased 5 months later. The change in blood lactate from rest to steady state during constant work rate exercise was significantly decreased after exercise training, but increased 5 months later. Measurement of the time constant of V?O₂ and oxygen pulse during constant work rate exercise are useful for the objective evaluation of the training effect of patients with COPD.     

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy

Background: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O₂ content (CaO₂). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long‐term O₂ therapy but present with exercise‐induced hypoxaemia and (ii) improve with hyperoxia (FIO₂ = 0·4) in this specific sub‐population. Methods: A total of 20 non‐hypercapnic men (FEV₁ = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold‐changes from unloaded exercise in O₂Hb) being determined by near‐infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO₂), and impedance cardiography estimated changes in cardiac output (ΔQT). Results: Peak work rate and ΔCOx in normoxia were lower in eight O₂‘desaturators’ compared with 12 ‘non‐desaturators’ (P<0·05). Area under ΔCOx during sub‐maximal exercise was closely related to SpO₂ decrements in ‘desaturators’ (r = 0·92, P<0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P<0·05). Despite a trend to lower sub‐maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for ‘non‐desaturators’ and ‘desaturators’, respectively; P<0·05). Conclusions: ΔCOx was impaired in non‐hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO₂ rather than improved central haemodynamics. This indicates that O₂ supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O₂ therapy.     

Influence of CYP2D6*10 on the pharmacokinetics of metoprolol in healthy Korean volunteers

Background and objective: Genetic polymorphism of CYP2D6 leads to differences in pharmacokinetics of CYP2D6 substrates. The CYP2D6*10 allele is clinically important in Koreans because of its high frequency in Asians. We investigated whether the pharmacokinetics of metoprolol was altered by the presence of the CYP2D6*10 allele in Korean subjects. Methods: One hundred and seven volunteers were recruited and grouped as CYP2D6*1/*1, CYP2D6*1/*10 and CYP2D6*10/*10 according to their genotypes. Metoprolol tartrate 100 mg (Betaloc^®) was administered orally once to each subject in these three groups (n = 6, 7 and 5, respectively). The pharmacokinetic parameters of metoprolol and its metabolite, α‐hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared. Results and discussion: The area under the plasma concentration–time curve (AUC_0→∞), the maximum plasma concentration (C_max) and the elimination half‐life (T_1/2) of metoprolol and α‐hydroxymetoprolol for the CYP2D6*10/*10 group were all significantly different from those of the CYP2D6*1/*1 group (P < 0·05). The AUC_0→∞s of metoprolol were 443·7 ± 168·1, 995·6 ± 321·4 and 2545·3 ± 632·0 ng·h/mL, and the AUC_0→∞s of α‐hydroxymetoprolol were 1232·0 ± 311·2, 1344·0 ± 288·1 and 877·4 ± 103·4 ng·h/mL for groups CYP2D6*1/*1, *1/*10 and *10/*10, respectively. The corresponding T_1/2 values of metoprolol were 2·7 ± 0·5, 3·2 ± 1·3 and 5·0 ± 1·1 h, while those of α‐hydroxymetoprolol were 5·4±1·5, 6·0 ± 1·4 and 10·5 ± 4·2 h, respectively. The metabolic ratios of the three groups were significantly different (P < 0·05). Conclusion: The CYP2D6*10 allele altered the pharmacokinetics of metoprolol in Korean subjects and is likely to affect other drugs metabolized by the CYP2D6 enzyme, similarly.     

Day‐to‐day variation in oxygen consumption at submaximal loads during ergometer cycling by adolescents

The day‐to‐day variation in oxygen consumption (V˙O₂) during ergometer cycling by 20 healthy adolescents, 10 females and 10 males, was measured using indirect calorimetry. The two sets of measurements were performed on two consecutive days. Great care was taken to minimize possible disturbing factors. Cycling started at 50 and 100 W for female and male adolescents, respectively. The load was increased at a rate of 5 W 30 s^?1. In order to reach steady state, the load was kept constant for 3·5 min twice during the cycling session, at 100 and 130 W for the females and at 130 and 160 W for the males. Cycling continued until exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and males, respectively. At the maximal loads the day‐to‐day variation (±2 SD) in oxygen consumption (V˙O₂) was ±330 ml min^?1 for females and 390 ml min^?1 for males. At the submaximal loads the day‐to‐day variation in heart rate (HR) was 9·3 beats min^?1 (±2 SD) (coefficient of variation, CV=3·4% at 130 W) for both sexes. The day‐to‐day variation in oxygen consumption (V˙O₂) was ±199 ml min^?1 (±2 SD) at the different submaximal loads and did not differ between female and male adolescents (CV=5·7% at 130 W). This natural day‐to‐day variation must be taken into consideration when using a submaximal ergometer cycling test for the evaluation of physical capacity in the two sexes.     

Autonomic nervous function at rest in aerobically trained and untrained oldermen

Therelationship between aerobictraining, vagal influence on the heart and ageing was examined by assessing aerobic fitness andresting heart rate variability in trained and untrained older men. Subjects were 11 trained cyclistsand runners (mean age=6±61·6 years) and 11 untrained, age-matchedmen (mean age=66±1·2 years). Heart rate variability testing involvedsubjects lying supine for 25 min during which subjects’ breathing was paced andmonitored (7·5 breaths min^?1). Heart rate variability was assessedthrough time series analysis (HRV_ts) of the interbeat interval. Results indicated thattrained older men (3·55±0·21 l min^?1) hadsignificantly (P<0·05) greater VO _2maxthan that of control subjects (2·35±0·15 l min^?1).Also, trained older men (52±1·8 beats min^?1) hadsignificantly (P<0·05) lower supine resting heart rate than that of controlsubjects (65±4·2 beats min^?1). HRV_ts at highfrequencies was greater for trained men (5·98±0·22) than for untrainedmen (5·23±0·32). These data suggest that regular aerobic exercise inolder men is associated with greater levels of HRV_ts at rest.     

Non-invasive cardiac output assessment during moderate exercise: pulse contour compared with CO2 rebreathing

The arterial pulse contour method called Modelflow 2·1 calculates stroke volume continuously, beat to beat, from the non-invasive blood pressure signal measured by Finapres or Portapres. Portapres is the portable version of Finapres. The purpose of this study was to compare cardiac output (CO) calculated using Modelflow 2·1 (CO_mf) with CO obtained by the CO₂ rebreathing method (CO_re) during steady state at moderate exercise levels. Twelve subjects visited the laboratory twice and performed submaximal exercise on a bicycle ergometer at 20%, 40% and 60% of their individual peak power output (PO_peak). The averaged correlation between CO_mf and CO_re gives an r-value of 0·69, whereas the slope and intercept of the regression line were 1·06 and 1·65 respectively. The averaged difference between CO_mf and CO_re was 2·27 ± 3·9 l min^–1 (mean ± standard deviation). However, the test–retest difference between CO_mf and CO_re was 2·5 ± 3·1 and 0·5 ± 1·3 l min^–1 respectively. These results suggest that Modelflow 2·1 is not an accurate method for estimating CO from non-invasive blood pressure data collected by Portapres during exercise at up to 60% of the individual PO_peak corresponding with daily life activity.