Inter-test reliability for non-invasive measures of respiratory muscle function in healthy humans

The aims of this study were to quantify the inter-test reliability of several voluntary, non-invasive measures of respiratory muscle function and to determine the implications of these data for studies using a repeated-measures design. Systematic measurement differences were found for 50% of the variables (P0.05, t-tests). Nevertheless, 95% ratio limits of agreement for most measures proved acceptable and similar to those reported elsewhere. The random error component of the agreement ratios ranged from 1.047 to 1.149 for measures of pulmonary function in healthy subjects (n=46), 1.045 to 1.056 for maximum static respiratory pressures (n=24), 1.062 to 1.173 for measures relating to the maximum pressure-flow-power relationship (n=16–22), and 1.036 to 1.071 for measures relating to maximum incremental inspiratory muscle performance (n=12). The judgement that the limits of agreement were acceptable is supported by the sample-size calculations. Estimated sample sizes based upon an alpha level of 0.05 and a statistical power of 0.9 were mostly 11 for a repeated-measures experimental design, particularly for the larger effect sizes (5%). However, peak expiratory flow, the maximum rate of pressure development and the time constant of relaxation, require larger sample sizes to detect small within-group changes. In conclusion, the described protocols provide reliable measurements for most parameters of respiratory muscle function in healthy subjects. Furthermore, experiments utilising a within-subjects design lasting up to 3 weeks can be conducted with feasible sample sizes (11 per group) where substantial (5%) changes are expected.     

Effect of thoracic gas compression and bronchodilation on the assessment of expiratory flow limitation during exercise in healthy humans

Expiratory flow limitation (EFL) during exercise may be overestimated or falsely detected when superimposing tidal breaths within a pre-exercise maximal expiratory flow volume (MEFV) curve due to thoracic gas compression (TGC) and bronchodilation. Accordingly, the purpose of this study was to determine the effects of TGC and bronchodilation on the assessment of EFL in 35 healthy subjects. A pre-exercise forced vital capacity (FVC) maneuver was performed that did not account for TGC (MEFV_pre). Subjects then performed graded expirations from total lung capacity to residual volume at different efforts to account for TGC (MEFV_pre-TGC). Post-exercise FVC (MEFV_post) and post-exercise graded expirations (MEFV_post-TGC) were performed to account for bronchodilation and TGC. EFL occurred in 29 subjects when using MEFV_pre. The magnitude of EFL in these subjects was 47 ± 23% which was significantly higher than MEFV_pre-TGC (28 ± 28%), MEFV_post (24 ± 27%) and MEFV_post-TGC (19 ± 24%) (P < 0.00001). Using the traditional MEFV_pre curve overestimates and falsely detects EFL since it does not account for TGC and bronchodilation.     

Non-invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method

AIMS: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three-element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non-invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. METHODS: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi-stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. RESULTS AND CONCLUSION: The Modelflow-estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min-1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non-invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.     

Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral blood flow velocity in healthy humans

Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know how spontaneous fluctuations in BP and CO influence cerebral circulation throughout 24 h. We performed simultaneous monitoring of BP, systemic haemodynamic parameters and blood flow velocity in the middle cerebral artery (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded continuously during 24 h by Portapres and bilateral MCAV was measured by transcranial Doppler (TCD) during the first 15 min of every hour. The subjects remained supine during TCD recordings and during the night, otherwise they were seated upright in bed. Stroke volume (SV), CO and total peripheral resistance (TPR) were determined by Modelflow analysis. The 15 min mean value of each parameter was assumed to represent the mean of the corresponding hour. There were no significant differences between right vs. left, nor between mean daytime vs. night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV recordings showed marked variations (P < 0.001). Within each single 15-min recording period, however, MCAV was stable whereas BP showed significant short-term variations (P < 0.01). A day-night difference in BP was only observed when daytime BP was evaluated from recordings in the seated position (P < 0.02), not in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P < 0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV remains stable when measured under constant supine conditions but shows significant variations throughout 24 h because of activity. Moreover, changes in SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h.     

Influence of acute submaximal exercise on T-lymphocyte suppressor cell function in healthy young men

A defect in T-lymphocyte suppressor cell function has been reported to occur in a number of autoimmune diseases. The influence of exercise on suppressor cell function has not been determined in individuals with autoimmune diseases, nor has it been determined in healthy individuals. The purpose of this investigation was to determine the effect of an acute bout of submaximal exercise on suppressor cell function in healthy males. Each subject (n=10) completed an exercise trial (E; 1 h of cycle ergometry at 70.6% of maximal oxygen uptake, followed by 2 h of recovery) and a resting trial (R; 3 h of seated rest), separated by at least 1 week. Treatment (E or R) order was counterbalanced. Venous blood samples were obtained pre-exercise (PRE), immediately after exercise (POST), and 2 h post-exercise (2HPOST), and at the same time points in the R trial. Lymphocyte phenotype percentages were determined by flow cytometry, while concanavalin- A-induced suppressor cell function was determined on peripheral blood mononuclear cells. No change was observed in the percentage of T-cytotoxic/suppressor cells. Suppressor cell function was significantly different between treatments, with the POST E value [mean (SD) 56.8 (1.6)%] being higher than the POST R value [41.7 (1.9)%]. No significant difference was observed 2HPOST. In conclusion, acute submaximal exercise resulted in a transient increase in suppressor cell function in healthy males. Accepted: 17 January 2000     

Adaptation to chronic eccentric exercise in humans: the influence of contraction velocity

We compared changes in muscle fibre composition and muscle strength indices following a 10 week isokinetic resistance training programme consisting of fast (3.14 rad^.s^–1) or slow (0.52 rad^.s^–1) velocity eccentric muscle contractions. A group of 20 non-resistance trained subjects were assigned to a FAST (n=7), SLOW (n=6) or non-training CONTROL (n=7) group. A unilateral training protocol targeted the elbow flexor muscle group and consisted of 24 maximal eccentric isokinetic contractions (four sets of six repetitions) performed three times a week for 10 weeks. Muscle biopsy samples were obtained from the belly of the biceps brachii. Isometric torque and concentric and eccentric torque at 0.52 and 3.14 rad^.s^–1 were examined at 0, 5 and 10 weeks. After 10 weeks, the FAST group demonstrated significant [mean (SEM)] increases in eccentric [29.6 (6.4)%] and concentric torque [27.4 (7.3)%] at 3.14 rad^.s^–1, isometric torque [21.3 (4.3)%] and eccentric torque [25.2 (7.2)%] at 0.52 rad^.s^–1. The percentage of type I fibres in the FAST group decreased from [53.8 (6.6)% to 39.1 (4.4)%] while type IIb fibre percentage increased from [5.8 (1.9)% to 12.9 (3.3)%; P<0.05]. In contrast, the SLOW group did not experience significant changes in muscle fibre type or muscle torque. We conclude that neuromuscular adaptations to eccentric training stimuli may be influenced by differences in the ability to cope with chronic exposure to relatively fast and slow eccentric contraction velocities. Possible mechanisms include greater cumulative damage to contractile tissues or stress induced by slow eccentric muscle contractions. Electronic Publication     

Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans

We assessed segmental and global left ventricular (LV) diastolic function via tissue-Doppler imaging (TDI) as well as Doppler flow variables before and after a marathon race to extend our knowledge of exercise-induced changes in cardiac function. Twenty-nine subjects (age 18–62 year) volunteered to participate and were assessed pre- and post-race. Measurements of longitudinal plane TDI myocardial diastolic velocities at five sites on the mitral annulus included peak early myocardial tissue velocity ( E '), peak late (or atrial) myocardial tissue velocity ( A ') and the ratio E '/ A '. Standard pulsed-wave Doppler transmitral and pulmonary vein flow indices were also recorded along with measurements of body mass, heart rate, blood pressures and cardiac troponin T (cTnT), a biomarker of myocyte damage. Pre- to post-race changes in LV diastolic function were analysed by repeated measures ANOVA. Delta scores for LV diastolic function were correlated with each other and alterations in indices of LV loading. Diastolic longitudinal segmental and mean TDI data were altered post-race such that the mean E '/ A ' ratio was significantly depressed (1.51 ± 0.34 to 1.16 ± 0.35, P < 0.05). Changes in segmental and global TDI data were not related to an elevated post-race HR, a decreased post-race pre-load or an elevated cTnT. The pulsed wave Doppler ratio of peak early transmitral flow velocity ( E )/peak late (or atrial) flow velocity ( A ) was also significantly reduced post-race (1.75 ± 0.46 to 1.05 ± 0.30, P < 0.05); however, it was significantly correlated with post-race changes in heart rate. The lack of change in E / E ' from pre- to post-race (3.4 ± 0.8 and 3.3 ± 0.7, respectively) suggests that the depression in diastolic function is likely to be due to altered relaxation of the left ventricle; however, the exact aetiology of this change remains to be determined.     

Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DL_CO) and the components of DL_CO (pulmonary capillary blood volume V _c, and alveolar–capillary membrane conductance D _M) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m², peak normoxic VO₂ = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO₂ of 12.5% for 90 min. DLCO, V _c, and D _M were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O₂ saturation and VO_2peak did not differ between the two conditions. DL_CO was not different between groups at any time point. V _C was higher with exercise in the placebo group, and the difference in D _M between sildenafil and placebo was significant only when corrected for changes in V _c (D _M/V _c = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in D _M when corrected for changes in V _c during short-term hypoxic exposure with exercise.     

Ventilatory effects of biceps vibration during leg exercise in healthy humans

The ventilatory effects of biceps tendon vibration were studied in healthy human subjects at rest and at two levels of light leg exercise. This was performed with intent to add the ventilatory effects of selective stimulation of muscle spindles to nervous and humoral respiratory inputs from contracting muscles. Tendon vibration performed in individuals at rest elicited a marked increase in respiratory frequency and in the ratio between inspiratory time and total breath duration with variable changes in tidal volume; this was in agreement with previous results (Jammes et al., 1981). When stimulation of biceps proprioceptors was performed during steady state exercise, the changes in ventilatory timing were attenuated, but variations in tidal volume often occurred. These results suggest that, when respiratory centers are being entrained by performance of work, further activation of muscle receptors exerts complex effects on the breathing pattern with a lack of facilitatory influences in ventilation and gas exchange.     

Non‐invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method

Aims: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three‐element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non‐invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. Methods: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi‐stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. Results and Conclusion: The Modelflow‐estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min^?1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non‐invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.     

An instrument for the non-invasive assessment of lip function during speech

This paper describes the development of an instrument using infrared light as a non-invasive means of detecting lip opening, the extent of the opening and also the forward protrusion and backward movement of the lips during speech. The design criteria were to build a simple stand alone means of assessing lip function, which could also link to the group's commercially available Super Nasal-Oral Ratiometry System (SNORS+). SNORS+ allows objective assessment of the function and co-ordination of key articulators, with lip function previously monitored using a video camera. Synchronised tests were carried out using the new Lip Function Monitor and the video camera simultaneously, in order to verify that the signals produced related directly to the activity of the mouth. A small trial was then conducted to show that the system provides reproducible results throughout a range of 'normal' subjects. These subjects were of different gender and race to create a sample group within which there was a variety of lip sizes and face shapes. Technical aspects of the instrument and trial results are presented here. These suggest that the simple visual output and feedback of the instrument will prove useful in the assessment and management of speech disorders.     

Adhesion molecule expression in acute and chronic exercise

Adhesion molecules expressed on leukocytes and the vascular endothelial lining include the selectins, integrins, members of the immunoglobulin superfamily, and mucins. The changes in their expression that develop with acute and chronic exercise are briefly reviewed. Adhesion molecules are thought to modulate leukocyte trafficking, accounting for changes in the counts and possibly also the functional activity of various leukocyte subsets during and following an acute bout of physical activity. Some of the changes in the surface density of adhesion molecules can be explained through the action of epinephrine and other humoral factors on their expression, but an influence of sympathetic nerve terminals on cells sequestered in the spleen and liver, and an influx into the general circulation of leukocytes of differing phenotype also appear to be involved.     

Carotid chemoreceptor modulation of sympathetic vasoconstrictor outflow during exercise in healthy humans

Recently, we have shown that specific, transient carotid chemoreceptor (CC) inhibition in exercising dogs causes vasodilatation in limb muscle. The purpose of the present investigation was to determine if CC suppression reduces muscle sympathetic nerve activity (MSNA) in exercising humans. Healthy subjects ( N = 7) breathed hyperoxic gas ( F _IO2∼1.0) for 60 s at rest and during rhythmic handgrip exercise (50% maximal voluntary contraction, 20 r.p.m.). Microneurography was used to record MSNA in the peroneal nerve. End-tidal P _CO2 was maintained at resting eupnoeic levels throughout and breathing rate was voluntarily fixed. Exercise increased heart rate (67 versus 77 beats min⁻¹), mean blood pressure (81 versus 97 mmHg), MSNA burst frequency (28 versus 37 bursts min⁻¹) and MSNA total minute activity (5.7 versus 9.3 units), but did not change blood lactate (0.7 versus 0.7 m m ). Transient hyperoxia had no significant effect on MSNA at rest. In contrast, during exercise both MSNA burst frequency and total minute activity were significantly reduced with hyperoxia. MSNA burst frequency was reduced within 9–23 s of end-tidal P _O2 exceeding 250 mmHg. The average nadir in MSNA burst frequency and total minute activity was −28 ± 2% and −39 ± 7%, respectively, below steady state normoxic values. Blood pressure was unchanged with hyperoxia at rest or during exercise. CC stimulation with transient hypoxia increased MSNA with a similar time delay to that obtained with CC inhibition via hyperoxia. Consistent with previous animal work, these data indicate that the CC contributes to exercise-induced increases in sympathetic vasoconstrictor outflow.     

Effects of graded heat stress on global left ventricular function and twist mechanics at rest and during exercise in healthy humans

Increased left ventricular (LV) twist and untwisting (LV twist mechanics) contribute to the maintenance of stroke volume during passive heat stress. However, it remains unknown whether changes in LV twist mechanics are related to the magnitude of heat stress and whether performing exercise during heat stress alters this response. We examined global LV function and LV twist mechanics in 10 healthy men at baseline and three progressive levels of heat stress, at rest and during knee-extensor exercise. At rest, heat stress increased cardiac output and reduced end-diastolic volume and end-systolic volume, whilst stroke volume and mean arterial pressure (MAP) were maintained. Left ventricular twist and untwisting velocity also increased from baseline to severe heat stress (from 10.6 ± 3.3 to 15.1 ± 5.2 deg and from -123 ± 55 to -210 ± 49 deg s(-1), respectively, both P < 0.01) and correlated significantly with body temperature, heart rate and LV volumes (P < 0.05). Similar to resting conditions, progressive heat stress during exercise increased cardiac output and reduced end-diastolic volume and end-systolic volume with a maintained stroke volume. However, MAP declined (P < 0.01) and there was no significant change in LV twist and untwisting velocity, resulting in non-significant relationships between twist mechanics and systemic responses. In conclusion, LV twist mechanics increase proportionally with the magnitude of heat stress at rest. However, there is no increase in LV twist and untwisting velocity from control exercise to severe heat stress during exercise despite a significant increase in body temperatures and cardiac output. We, therefore, suggest that the maintenance of stroke volume in the combined conditions of heat stress and small muscle mass exercise may be further facilitated by other peripheral factors, such as the continuous decline in MAP.     

Oxygen kinetics and debt during recovery from expiratory flow-limited exercise in healthy humans

In healthy subjects expiratory flow limitation (EFL) during exercise can lower O(2) delivery to the working muscles. We hypothesized that if this affects exercise performance it should influence O(2) kinetics at the end of exercise when the O(2) debt is repaid. We performed an incremental exercise test on six healthy males with a Starling resistor in the expiratory line limiting expiratory flow to approximately 1 l s(-1) to determine maximal EFL exercise workload (W (max)). In two more square-wave exercise runs subjects exercised with and without EFL at W (max) for 6 min, while measuring arterial O(2) saturation (% SaO(2)), end-tidal pressure of CO(2) (P (ET)CO(2)) and breath-by-breath O(2) consumption VO2 taking into account changes in O(2) stored in the lungs. Over the last minute of EFL exercise, mean P (ET)CO(2) (54.7 +/- 9.9 mmHg) was significantly higher (P < 0.05) compared to control (41.4 +/- 3.9 mmHg). At the end of EFL exercise %SaO(2) fell significantly by 4 +/- 3%. When exercise stopped, EFL was removed, and we continued to measure VO2. During recovery, there was an immediate step increase in [Formula: see text] so that repayment of EFL O(2) debt started at a higher VO2 than control. Recovery VO2 kinetics after EFL exercise was best characterized by a double-exponential function with fundamental and slow time constants of 27 +/- 11 and 1,020 +/- 305 s, compared to control values of 41 +/- 10 and 1,358 +/- 320 s, respectively. EFL O(2) debt was 52 +/- 22% greater than control (2.19 +/- 0.58 vs. 1.49 +/- 0.38 l). We conclude that EFL exercise increases the O(2) debt and leads to hypoxemia in part due to hypercapnia.     

Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

An important determinant of [H⁺] in the environment of the central chemoreceptors is cerebral blood flow. Accordingly we hypothesized that a reduction of brain perfusion or a reduced cerebrovascular reactivity to CO₂ would lead to hyperventilation and an increased ventilatory responsiveness to CO₂. We used oral indomethacin to reduce the cerebrovascular reactivity to CO₂ and tested the steady-state hypercapnic ventilatory response to CO₂ in nine normal awake human subjects under normoxia and hyperoxia (50% O₂). Ninety minutes after indomethacin ingestion, cerebral blood flow velocity (CBFV) in the middle cerebral artery decreased to 77 ± 5% of the initial value and the average slope of CBFV response to hypercapnia was reduced to 31% of control in normoxia (1.92 versus 0.59 cm⁻¹ s⁻¹ mmHg⁻¹, P < 0.05) and 37% of control in hyperoxia (1.58 versus 0.59 cm⁻¹ s⁻¹ mmHg⁻¹, P < 0.05). Concomitantly, indomethacin administration also caused 40–60% increases in the slope of the mean ventilatory response to CO₂ in both normoxia (1.27 ± 0.31 versus 1.76 ± 0.37 l min⁻¹ mmHg⁻¹, P < 0.05) and hyperoxia (1.08 ± 0.22 versus 1.79 ± 0.37 l min⁻¹ mmHg⁻¹, P < 0.05). These correlative findings are consistent with the conclusion that cerebrovascular responsiveness to CO₂ is an important determinant of eupnoeic ventilation and of hypercapnic ventilatory responsiveness in humans, primarily via its effects at the level of the central chemoreceptors.     

Plasma adiponectin response to acute exercise in healthy subjects

Adipose tissue secretes adiponectin, an adipocytokine that is involved in the regulation of insulin sensitivity. Following acute exercise, insulin sensitivity has been shown to increase. Increased adiponectin following exercise may be related to the change in insulin sensitivity. The purpose of the present study was to characterize the effect of a single cycle exercise session on adiponectin and to compare the exercise effects between healthy male and female subjects. Plasma concentrations of adiponectin, tissue necrosis factor-alpha (TNF-), insulin, glucose, and leptin were assessed before and immediately after a 60-minute stationary cycle ergometry session at 65% of O_2max. Male and female subjects were matched for cardiorespiratory fitness and body composition and dietary intake was controlled for the three days prior to the exercise trial. At rest, adiponectin concentration was not associated with percentage body fat, body mass index (BMI), fitness, or resting plasma variables (P>0.05). Following exercise, neither male nor female subjects exhibited changes in adiponectin or leptin concentrations (P>0.05). TNF- exhibited a time main effect increase with exercise (P<0.05), but there were no gender differences. These results suggest that plasma adiponectin concentrations do not change with exercise in healthy male or female subjects. Results are given as mean (SE).