Effect of hypoxia on muscle oxygenation and metabolism during arm exercise in humans

Summary. The influence of hypoxaemia on anaerobic energy production during arm exercise (AE) has been investigated. Six men were studied during maximal AE and during 10 min of sitting submaximal AE under both normoxic (AEN) and hypoxic (AEH, respiratory hypoxia, 12% O2) conditions. Peak pulmonary oxygen uptake (VO₂) during maximal AE in normoxia and hypoxia was 2.25±0.15 and 2–18±014 1 min^-1, respectively (P<0.05). The absolute workload was the same during submaximal AEN and AEH and corresponded to 54% of peak VO₂ during normoxic maximal AE. To eliminate the potential influence of differences in catecholamine levels on the metabolic response, the submaximal experiments were performed during β-adrenoceptor blockade. Oxygen deficit was.,45±0–26 and 1.67±0191 during AEN and AEH, respectively (n.s.). Oxygen extraction at steady state was lower during AEH than during AEN, and assuming a similar O₂ demand this corresponds to a 14% higher muscle blood flow during AEH. At the onset of both AEN and AEH, O₂ extraction (a-v O₂) across the arm increased transiently above that at steady state, the increase being more pronounced during AEN than during AEH (P<0–05). Muscle oxygenation, measured by near-infrared spectroscopy, demonstrated an initial decrease which was partially reversed as exercise proceeded. The reversal of muscle O₂ desaturation was slower in all subjects during AEH (t_1/2=2.4±0.2 min) than during AEN (t_1/2=1.2±0–2 min; P<0–01). After 10 min of exercise, arterial blood lactate was higher (P<0–05) during AEH (5.5 ±0.2 mmol 1^-1) than during AEN (4.9±0.6 mmol 1^-1), whereas arterial plasma ammonia (NH₃) was similar. The arteriovenous difference for both lactate and ammonia was similar during AEN and AEH. It is concluded that the high anaerobic energy production at the onset of AE is associated with a transient increase in O₂ extraction and a transient decrease in muscle oxygenation. The effects of hypoxaemia on peak VO₂, oxygen deficit and blood metabolites are less pronounced than previously described during submaximal leg exercise (LE).     

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.     

ATP breakdown products in human skeletal muscle during prolonged exercise to exhaustion

Summary. To study changes in muscle energy state during prolonged exercise, especially in relation to fatigue, muscle biopsies were obtained from seven healthy males working until exhaustion on a cycle ergometer at 68% (63–74%) of their maximal oxygen uptake. Biopsies were taken at rest, after 15 and 45 min of exercise and at exhaustion, and analysed for ATP, ADP, AMP, inosine monophosphate (IMP) and hypoxanthine content by high performance liquid chromatography (HPLC), and for creatine phosphate (CP), lactate and glycogen by enzymatic fluorometric techniques. Glycogen content at exhaustion was approximately 30% of the pre-exercise level. The CP content decreased steeply during the first 15 min of exercise (P<0·01) and continued to decrease during the rest of the exercise period (P<0·05). Pronounced increases in contents of IMP (64%P<0·001) and hypoxanthine (69%, P<0·05) were found when exhaustion was approaching. Furthermore, energy charge [EC; (ATP+0·5 ADP)/(ATP+ADP+AMP)] was decreased at exhaustion (P<0·05). The increases in IMP and hypoxanthine which occurred when exhaustion was approaching during prolonged submaximal exercise together with the decrease in EC during this phase of exercise suggest a failure of the exercising skeletal muscle to regenerate ATP at exhaustion.     

Does post-tetanic potentiation compensate for low frequency fatigue?

Summary. The purpose of this study was to examine the effect of post-tetanic potentiation on low frequency fatigue in adult human quadriceps muscle. Sixteen subjects (10 male and six female) performed three 60 s sets of knee extension exercise in order to induce low frequency fatigue (reduction in torque output at 10 and 20 Hz). The potentiating stimulus (a 10 s maximal voluntary contraction) induced a 58% increase in twitch tension (P_t) during the pre-fatigue state. Immediately following the fatiguing exercise, torque (X± SE, Nm) at 10 and 20 Hz (submaximal transcutaneous stimulation, 50 μs pulses) decreased (P<0·05) from 54·8 ± 5·8 and 94·9 ± 9·6 to 40·3 ± 6·1 and 77·0 ± 11, respectively. Although potentiation at this time increased P, from 40·9 ± 4·0 to 54·8 ± 3·7 (P<0·05), torque at 10 and 20 Hz was unaffected. At 60, 120 and 240 min post-contraction, torque at 10 and 20 Hz remained depressed. Following potentiation, which increased twitch tensions to between 64 and 75%, torque at 10 Hz was increased (P<0·05) at 60 min (36·3 ± 4·1 vs. 50·7 ± 6·2), 120 min (40·8 ± 6·3 vs. 56·5 ± 8·9) and 240 min (42·0 ± 4·7 vs. 57·5 ± 8·3) of recovery. Similar effects were also noted at 20 Hz. These findings indicate that post-tetanic potentiation can overcome the low frequency fatigue during the post-contraction period and restore torque to pre-exercise levels.     

Contractile properties of the human triceps surae following prolonged exercise and β-blockade

Summary. Sixteen healthy males volunteered to perform both an incremental maximal and prolonged submaximal treadmill test with β-blockade (2 × 80 mg oral propranolol per day) or matched placebo in a blind crossover design. Prior to and following the prolonged exercise, electrical stimulation of the triceps surae was performed to examine contractile properties. During the maximal test, the heart rate (HR) was reduced at all times by β-blockade. The time to exhaustion in this test was significantly reduced by β-blockade (P < 0·03), while the maximal oxygen uptake (VO_2max) was not significantly lower (P= 0·06). In response to prolonged treadmill walking at 60% of VO_2max, the HR was reduced but VO₂, respiratory quotient and ventilation were not affected by β-blockade relative to placebo. Plasma concentrations of free fatty acids increased during exercise in the placebo but not β-blocked treatment (P < 0·0001). Plasma noradrenalin and adrenalin increased with exercise; the increase in adrenalin with β-blockade was greater than that with placebo (P < 0·001). The RPE obtained at intervals during the prolonged exercise were greater for β-blockades than placebo. Eight of 16 subjects were unable to complete full 90 min with β-blockade; but all 16 completed the test with placebo. The electrically evoked twitches in the triceps surae muscle group after exercise did not differ in peak torque or one-half relaxation time compared to pre-exercise. The time to peak twitch torque was significantly shorter after exercise. No differences in twitch were observed due to β-blockade. The tetanic responses at 10, 20, 50 and 100 Hz were not affected by either exercise or the β-blockade. In conclusion, an increased subjective estimate of fatigue (RPE) was observed during prolonged exercise with β-blockade. This subjective fatigue did not relate to altered peripheral muscle force production during electrical stimulation. The results suggest either a central rather than peripheral origin of fatigue, or fatigue in a muscle group not examined by stimulation of the triceps surae.     

Effects of varying central command and muscle mass on the cardiovascular responses to isometric exercise

To determine if the central command signal associated with isometric exercise is mass‐dependent, 20 subjects (nine male, 11 female; 23 ± 1 years) performed four 5‐min bouts of supine isometric exercise with a large (quadriceps; LEG) and small (forearm; ARM) muscle mass. For each extremity, one bout entailed maintaining a constant force (CF; 20% maximal voluntary contraction) and the other constant electromyographic activity (CE; ~20% MVC initially). Central command was assumed to increase with CF and remain unchanged with CE. Heart rate increased more with LEG than ARM (P<0·001) and, in LEG, was higher in CF than CE at min 5 (P<0·001). Mean arterial pressure was higher in LEG (P<0·001) by min 2 and 10 ± 3 mmHg higher in LEG CF than LEG CE by min 5 (P<0·001). Ratings of perceived exertion were highest in LEG CF (P<0·001); LEG CE did not differ from ARM CE (P<0·001) by min 4. The ARM responses did not differ between CF and CE in any variable. These data suggest that muscle mass influences the central command signal during isometric exercise and central command modulates this response in larger muscle masses.     

Acute physiological and perceptual responses to high‐load resistance exercise in hypoxia

This study assessed whether hypoxia during high‐load resistance exercise could enhance the acute physiological responses related to muscular development. Twelve trained men performed exercise in three conditions: normoxia (fraction of inspired oxygen [F_IO₂] = 21%), moderate‐level hypoxia (F_IO₂ = 16%) and high‐level hypoxia (F_IO₂ = 13%). Exercise comprised high‐load squats and deadlifts (5 × 5 using 80% of 1‐repetition maximum with 180‐s rest). Muscle oxygenation and activation were monitored during exercise. Metabolic stress was estimated via capillary blood sampling. Perceived fatigue and soreness were also quantified following exercise. While the hypoxic conditions appeared to affect muscle oxygenation, significant differences between conditions were only noted for maximal deoxyhaemoglobin in the deadlift (P = 0·009). Blood lactate concentration increased from 1·1 to 1·2 mmol l^?1 at baseline to 9·5–9·8 mmol l^?1 after squats and 10·4–10·5 mmol l^?1 after deadlifts (P≤0·001), although there were no between‐condition differences. Perceived fatigue and muscle soreness were significantly elevated immediately and at 24 h following exercise, respectively, by similar magnitudes in all conditions (P≤0·001). Muscle activation did not differ between conditions. While metabolic stress is thought to moderate muscle activation and subsequent muscular development during hypoxic resistance training, it is not augmented during traditional high‐load exercise. This may be explained by the low number of repetitions performed and the long interset rest periods employed during this training. These findings suggest that high‐load resistance training might not benefit from additional hypoxia as has been shown for low‐ and moderate‐load training.     

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.     

The relationship between exercise‐induced muscle fatigue,arterial blood flow and muscle perfusion after 56 days local muscle unloading

In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work‐related power deficit (WoRPD) as a measure for exercise‐induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near‐infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (P<0·001) and soleus fibre size was reduced by 8·5 ± 13% (P = 0·016). However, WoRPD remained unaffected as indicated by an unchanged loss of relative plantar flexor power between pre‐ and postexperiments (P = 0·88). Blood flow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise‐induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability.     

Muscle glycogen concentration during recovery after prolonged severe exercise in fasting subjects

The influence of 12 h of fasting after prolonged severe exercise on the muscle glycogen concentration was studied in 5 normal subjects. The subjects exercised in the post absorptive state at 70% of max. V_o2 till exhaustion, then rested for 12 h. No food was allowed during recovery. Blood samples and muscle biopsies were obtained before exercise, immediately after the cessation of exercise, and after 2, 4, 6, 9 and 12 h of recovery. Muscle glycogen content decreased from 70.4 ± 3.0 to 21.6 ±3.9 mmol glucosyl units/kg w.w. in response to exercise. After 4 h of recovery muscle glycogen had increased to 28.8 + 3.6 mmol glucosyl units/kg (P<0.025). During the next 8 h of recovery no further increase in glycogen concentration was observed. Mean plasma glucose concentration decreased from 5.25±0.16 to 4.37±0.18 mmol/1 during exercise (P<0.001). No change in the plasma glucose level was observed during recovery. Immunoreactive insulin (IRI) concentration decreased from 15.9±1.0 to 10.2±0.5 μU/ml (P<0.001) during exercise, and remained at this level during recovery. It is concluded that some muscle glycogen repletion may occur after prolonged, severe exercise even under fasting conditions. It is suggested that this may proceed through an increased hepatic gluconeogenesis.     

Forearm composition and muscle function in trained and untrained limbs

Summary. The influence of a period of training, which lasts for several years, on the proportions of muscle, fat and bone present in the human forearm has been investigated by comparing trained and untrained limbs of nine experienced male tennis players. Ten healthy but untrained males of similar age served as a control group. Computed tomography (CT) scans of the forearm were made at intervals along its length to identify fat, muscle and bone and to calculate the volumes occupied by each of these components. Total forearm volume was greater in the dominant limb compared with the contralateral side in both trained (by 135±59 cm³, mean±SD, P<0·001) and untrained subjects (by 41±45 cm³, P<0·02). Forearm muscle volume was also greater in dominant limbs of trained (by 117±52 cm³, P<0·001) and untrained by 35±41 cm³, P<0·025) subjects. Muscle accounted for 75·4±2·7% of the total volume in the dominant arm of trained subjects compared with 71·4±4·2% in the control group (P<0·05). There was a greater proportion of muscle (P<0·05) and a smaller proportion of fat (P<0·001) in the trained limb compared with the contralateral limb of the same subjects. No differences in proportions of fat, muscle and bone were observed in dominant and non-dominant limbs of the control subjects. Trained subjects were able to exert a greater isometric force with the dominant limb (549±76N) than with the non-dominant limb (496±48N; P<0·005). There was no difference in grip strength between the arms of the untrained group (dominant: 516±107N; non-dominant: 491±91N). The ratio of strength to muscle volume was, however, the same in dominant and non-dominant arms of both groups of subjects.     

Muscular adaptations to fatiguing exercise with and without blood flow restriction

The purpose of this study was to determine the muscular adaptations to low‐load resistance training performed to fatigue with and without blood flow restriction (BFR). Middle‐aged (42–62 years) men (n = 12) and women (n = 6) completed 18 sessions of unilateral knee extensor resistance training to volitional fatigue over 6 weeks. One limb trained under BFR, and the contralateral limb trained without BFR [free flow (FF)]. Before and after the training, measures of anterior and lateral quadriceps muscle thickness (MTh), strength, power and endurance were assessed on each limb. The total exercise training volume was significantly greater for the FF limb compared with the BFR limb (P<0·001). Anterior quadriceps thickness and muscle function increased following the training in each limb with no differences between limbs. Lateral quadriceps MTh increased significantly more (P<0·05) in the limb trained under BFR (BFR: 3·50 ± 0·61 to 3·67 ± 0·62 cm; FF: 3·49 ± 0·73 to 3·56 ± 0·70 cm). Low‐load resistance training to volitional fatigue both with and without BFR is viable options for improving muscle function in middle‐aged individuals. However, BFR enhanced the hypertrophic effect of low‐load training and reduced the volume of exercise needed to elicit increases in muscle function.     

Fatigue and rapid hamstring/quadriceps force capacity in professional soccer players

The aim of this study was to investigate the effect of fatigue induced by an exhaustive laboratory‐based soccer‐specific exercise on different hamstrings/quadriceps (H:Q) ratios of soccer players. Twenty‐two male professional soccer players (23·1 ± 3·4 year) performed maximal eccentric (ecc) and concentric (con) contractions for knee extensors (KE) and flexors (KF) at 60° s^?1 and 180° s^?1 to assess conventional (H_con:Q_con) and functional (H_ecc:Q_con) ratios. Additionally, they performed maximal voluntary isometric contraction for KE and KF, from which the maximal muscle strength, rate of force development (RFD) and RFD H:Q strength ratio (RFDH:Q) were extracted. Thereafter, subjects were performed an exhaustive laboratory‐based soccer‐specific exercise and a posttest similar to the pretest. There was significant reduction in H_con:Q_con (0·60 ± 0·06 versus 0·58 ± 0·06, P<0·05) and in H_ecc:Q_con (1·29 ± 0·2 versus 1·16 ± 0·2, P<0·01) after the soccer‐specific exercise. However, no significant difference between Pre and Post exercise conditions was found for RFDH:Q at 0–50 (0·53 ± 0·23 versus 0·57 ± 0·24, P>0·05) and 0–100 ms (0·53 ± 0·17 versus 0·55 ± 0·17, P>0·05). In conclusion, H:Q strength ratios based on peak force values are more affected by fatigue than RFDH:Q obtained during early contraction phase. Thus, fatigue induced by soccer‐specific intermittent protocol seems not reduce the potential for knee joint stabilization during the initial phase of voluntary muscle contraction.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

Summary. The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68±3% of their VO₂ max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136±13 min v. 1st test: 110±12 min, P<0·01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137±13 min) than with either fructose (114±12 min) or water (116±13 min) (both P<0·01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467±29 mmol kg d.w.^-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P<0·05) with the ingestion of glucose (1·3±0·4 mmol kg d.w.^-1 min^-1) as compared to fructose (2·1±0·5 mmol kg d.w.^-1 min^-1) or water (2·3±0·5 mmol kg d.w.^-1 min^-1). Intermittent glucose ingestion (3×17·5 g h^-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Blood glucose concentration dependent ACTH and cortisol responses to prolonged exercise

Summary. The purpose of this study is to investigate responses of serum ACTH and cortisol concentration to low intensity prolonged exercise. In experiment 1, 10 subjects fasted for 12 h and performed bicycle exercise at 49·3%V?O₂max (±4·3%) until exhaustion or up to 3 h. During the early part of the exercise, serum ACTH and cortisol concentrations did not increase from the pre-exercise values (ACTH: 44±5 μg/1, cortisol: 139±52 μg/1). Whilst the time to serum ACTH concentration increasing varied among the subjects (60·180 min), the increases of this hormone occurred for all subjects (175±85 ng/1, P<0·05) when blood glucose concentration decreased to a critical level of 3·3 mmol/1. At the end of the exercise, blood glucose concentration decreased to 2·60±0·21 mmol/1, and serum ACTH and cortisol concentrations increased to 313±159 μg/1 and 371±151 μg/1, respectively. In experiment 2, four subjects performed the same intensity exercise until exhaustion, and were then given 600 ml of 20 g glucose solution, and immediately afterwards, they were asked to repeat the same exercise. The subjects continued the exercise for between 30 to 90 min until again reaching exhaustion. During the second exercise, blood glucose concentration increased to the pre-exercise value (2·72±0·58 to 4·00±0·22 mmol/1, P<0·05) and simultaneously, serum ACTH concentration decreased considerably (354±22 to 119±54 ng/1, P<0·05). The results of the present study suggest that serum ACTH and cortisol concentration during low intensity prolonged exercise may be dependent on blood glucose concentration.     

Measurement of cardiac output with non-invasive Aesculon impedance versus thermodilution

Background: This study compared the non‐invasive thoracic electrical bioimpedance Aesculon^® technique (TEB_Aesculon) with thermodilution (TD) to evaluate whether TEB_Aesculon may offer a reliable means for estimating cardiac output (CO) in humans. Material and method: Cardiac output was measured with TD and TEB_Aesculon in 33 patients, with a mean age ± SEM of 59 ± 2·7 years, that underwent right heart catheterization for clinical investigation of pulmonary hypertension or severe heart failure. Four to five CO measurements were performed with each technique simultaneously in 33 patients at rest, 11 during exercise and seven during NO inhalation. Result: Cardiac output correlated poorly between TEB_Aesculon and TD at rest (r = 0·46, P<0·001), during exercise (r = 0·35, P<0·013) and NO inhalation (r = 0·41, P<0·017). CO was higher for TEB_Aesculon than TD with 0·86 ± 0·14 l min^?1 at rest (P<0·001) and 2·95 ± 0·69 l min^?1 during exercise (P<0·003), but similar during NO inhalation, with a tendency (P<0·079) to be 0·44 ± 0·19 l min^?1 higher for TEB_Aesculon than TD. CO increased from rest to exercise for TEB_Aesculon and TD with 6·11 ± 0·6 l min^?1 (P<0·001) and 3·91 ± 0·36 l min^?1 (P<0·001), respectively; an increase that was higher (P<0·002) for TEB_Aesculon than TD. During NO inhalation, compared to rest, CO decreased for TEB_Aesculon with 0·62 ± 0·11 l min^?1 (P<0·002), but not significantly for TD with 0·21 ± 0·12 l min^?1 (P<0·11). Bland–Altman analysis showed a poor agreement between TEB_Aesculon and TD. Conclusion: TEB_Aesculon overestimated CO compared to TD with ～17% at rest and ～34% during exercise, but the techniques showed similar results during NO inhalation. CO, furthermore, correlated poorly between TEB_Aesculon and TD. TEB_Aesculon may at present not replace TD for reliable CO measurements in humans.     

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.     

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.     

Influence of exercise intensity on systemic oxidative stress and antioxidant capacity

The aim of the current study was to examine the influence of exercise intensity on systemic oxidative stress (OS) and endogenous antioxidant capacity. Non‐smoking, sedentary healthy adult males (n = 14) participated in two exercise sessions using an electronically braked cycle ergometer. The first session consisted of a graded exercise test to determine maximal power output and oxygen consumption (VO_2max). One week later, participants undertook 5‐min cycling bouts at 40%, 55%, 70%, 85% and 100% of VO_2max, with passive 12‐min rest between stages. Measures of systemic OS reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), heart rate (HR), VO₂, blood lactate and rating of perceived exertion were assessed at rest and immediately following each exercise stage. Significant (P<0·05) differences between exercise bouts were examined via repeated measures ANOVA and post hoc pairwise comparisons with Bonferroni correction. Increasing exercise intensity significantly augmented HR (P<0·001), VO₂ (P<0·001), blood lactate (P<0·001) and perceived exertion (P<0·001) with no significant effect on dROM levels compared with resting values. In contrast, increasing exercise intensity resulted in significantly (P<0·01) greater BAP at 70% (2427 ± 106), 85% (2625 ± 121) and 100% (2651 ± 92) of VO_2max compared with resting levels (2105 ± 57 μmol Fe²⁺/L). The current results indicate that brief, moderate‐to‐high‐intensity exercise significantly elevates endogenous antioxidant defences, possibly to counteract increased levels of exercise‐induced reactive oxygen species. Regular moderate‐to‐high‐intensity exercise may protect against chronic OS associated diseases via activation, and subsequent upregulation of the endogenous antioxidant defence system.     

Myocardial perfusion defects in Bartter and Gitelman syndromes

Background Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events. Patients and methods Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two‐dimensional and myocardial contrast echocardiography. Results BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 ± 9·1 ms (P < 0·001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 ± 4% to 78 ± 5%, P < 0·003) while in seven BS/GS patients (Group 1) it declined (64 ± 5% to 43 ± 9%, P < 0·001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: β (a measure of myocardial flow velocity; 0·89 ± 0·12 vs. 0·99 ± 0·12, P < 0·001) and myocardial blood volume (14·4 ± 2 vs. 20·2 ± 0·25, P < 0·001), while in Group 1 BS/GS it decreased (0·87 ± 0·15 vs. 0·67 ± 0·15, P < 0·001; and 14·5 ± 1·9 vs. 8·3 ± 0·22, P < 0·001, respectively). Conclusions Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in‐depth cardiac assessment in order to identify patients at higher risk.