Transfer Impedance of the Respiratory System by Forced Oscillation Technique and Optoelectronic Plethysmography

To estimate the transfer impedance of the respiratory system we applied pressure forcing at the mouth from 1 to 24 Hz in eight healthy subjects and used optoelectronic plethysmography (OEP) to measure volume changes of the chest wall and its different compartments: pulmonary rib cage abdominal rib cage and abdomen (AB). Spectral analysis allowed assessment of input impedance and total and compartmental and transfer impedances. As expected, averaged values of and were similar at low frequencies (<8 Hz) while they progressively differed at high frequencies. The percentage contributions of and to were, respectively, 35.3±1.4SD, 13.8±1.4, and 50.8±2.8 at low frequencies (<8 Hz) and 63.1±5.5, 20.7±5.2, and 16.2±2.3 at higher frequencies (>10 Hz). The validation of our approach was based on the comparison with a physical model comprised of a rubber membrane stretched over and attached to the lip of a bowl. We conclude that the combination of forced oscillations with OEP provides the simultaneous assessment of and it does not require the use of a plethysmographic chamber and it allows the separation between the different rib cage-abdominal pathways. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 8780-y, 8763Lk     

Effect of Within-Strain Sample Size on QTL Detection and Mapping Using Recombinant Inbred Mouse Strains

Increasing the number of mice used to calculate recombinant inbred (RI) strain means increases the accuracy of determining the phenotype associated with each genotype (strain), which in turn enhances quantitative trait locus (QTL) detection and mapping. The purpose of this paper is to examine quantitatively the effect of within-strain sample size (n) on additive QTL mapping efficiency and to make comparisons with F₂and backcross (BC) populations, where each genotype is represented by only a single mouse. When 25 RI strains are used, the estimated equivalent number of F₂mice yielding the same power to detect QTLs varies inversely as a function of the heritability of the trait in the RI population . For example, testing 25 strains with n= 10 per strain is approximately equivalent to 160 F₂mice when = 0.2, but only 55 when = 0.6. While increasing nis always beneficial, the gain in power as nincreases is greatest when is low and is much diminished at high values. Thus, when is high, there is little advantage of large n, even when napproaches infinity. A cost analysis suggested that RI populations are more cost-effective than conventional selectively genotyped F₂populations at values likely to be seen in behavioral studies. However, with DNA pooling, this advantage is greatly reduced and may be reversed depending on the values of and n.     

Tissue Plasminogen Activator (tPA) Inhibits Human Neutrophil Superoxide Anion Production in Vitro

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide ( ) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil production.     

Aerobic power and pubertal peak height velocity in Belgian boys

Summary To determine the cardiorespiratory response to maximal exercise before, during and after the pubescent growth spurt, thirty boys were tested at yearly intervals over a period of six consecutive years. For each individual, peak height velocity (PHV) was determined. The age at PHV (¯X= 13.6 years) was taken as a standard of maturation. The results from all subjects at 1.5 and 0.5 years before and 0.5 and 1.5 years after PHV are presented. The highest oxygen uptake ( ) obtained during an incremental bicycle ergometer test to voluntary exhaustion was taken as peak oxygen uptake ( peak). Across each of the four years studied, mean peak (min=49.6; max=52.5 ml·kg^–1·min^–1) and mean heart rate (HR) at peak (min=190; max=192) did not change significantly as a function of PHV. On the other hand, the respiratory quotient at peak increased considerably from mean minima and maxima of 0.99 and 1.01 before PHV to 1.07 and 1.10 after PHV. Ventilatory equivalent for ( ), taken as an indicator of ventilatory economy, seemed to be unaffected by the maturation process. The steepest increase in circumpubertal oxygen pulse was found one year after PHV. Average stability coefficients (¯r), calculated from the inter-years correlations were high for height (¯r=0.95), weight (¯r=0.92), HR at peak (¯r=0.74), peak in 1/min (¯r=0.71), oxygen pulse (¯r=0.68) and tidal volume (¯r=0.64).     

Central hypoxic-hypercapnic interaction in mild hypoxia in man

Hypoxic-hypercapnic interaction in mild hypoxia was studied in 12 healthy males. Steady state ventilatory responses to hypercapnic-hypoxia were obtained as the difference in ventilation between hypoxia (mean values ± S.D. of =7.36±0.20 kPa or of 7.10 ±0.41 kPa) and hyperoxia ( >26.7 kPa) with the same degree of hypercapnia ( 6.12±0.22 kPa). On the other band, withdrawal responses were obtained as the magnitude of depression in ventilation caused by two bicaths of O₂ from the above mentioned hypoxic hypercapnia. Averaged and were 9.57±5.45 and 6.45 ±4.90l/min, respectively, the difference being statistically significant (P<0.01). Furthermore, if we assume the presence of ventilatory depression to be due to tissue fall resulting from an increase in cerebral blood flow caused by hypoxia, the magnitude of central hypoxic-hypercapnic interaction was estimated to be as great as the value of .     

Total muscle mitochondrial volume in relation to aerobic capacity of horses and steers

The relationship between maximal oxygen consumption rate ( ) and mitochondrial content of skeletal muscles was examined in horses and steers (n=3 each). Samples of the heart left ventricle, diaphragm,m. vastus medialis, m. semitendinosus, m. cutaneous thoracicus andm. masseter, as well as samples of muscles collected in a whole-body sampling procedure, were analyzed by electron microscopy. per kilogram body mass was 2.7× greater in horses than steers. This higher was in proportion to the higher total volume of mitochondria in horse versus steer muscle when analyzed from the whole-body samples and from the locomotor muscle samples. In non-locomotor muscles, total mitochondrial volume was greater in horses than steers, but not in proportion to their differences in . The of the mitochondria was estimated to be close to 4.5 ml O₂·ml^–1 mitochondria in both species. It is concluded that in a comparison of a highly aerobic to a less aerobic mammalian species of similar body size, a higher oxidative potential may be found in all muscles of the more aerobic species. This greater oxidative potential is achieved by a greater total volume of skeletal muscle mitochondria.     

Changes in skeletal muscle oxygenation during incremental exercise measured with near infrared spectroscopy

To determine the change in muscle oxygenation in response to progressively increasing work rate exercise, muscle oxyhemoglobin + oxymyoglobin saturation was measured transcutaneously with near infrared spectroscopy in the vastus lateralis muscle during cycle ergometry. Studies were done in 11 subjects while gas exchange was measured breath-by-breath. As work rate was increased, tissue oxygenation initially either remained constant near resting levels or, more usually, decreased. Near the work rate and metabolic rate where significant lactic acidosis was detected by excess CO₂ production (lactic acidosis threshold, LAT), muscle oxygenation decreased more steeply. As maximum oxygen uptake ( ) was approached, the rate of desaturation slowed. In 8 of the 11 subjects, tissue O₂ saturation reached a minimum which was sustained for 1–3 min before was reached. The LAT correlated with both the (r = 0.95,P < 0.0001) and the work rate (r = 0.94,P < 0.0001) at which the rate of tissue O₂ desaturation accelerated. These results describe a consistent pattern in the rate of decrease in muscle oxygenation, slowly decreasing over the lower work rate range, decreasing more rapidly in the work rate range of the LAT and then slowing at about 80% of , approaching or reaching a minimum saturation at .     

Factors which alter the relationship between ventilation and carbon dioxide production during exercise in normal subjects

The slope of the linear relationship between ventilation and carbon dioxide production has been thought to indicate that is one of the major stimuli to . A group of 15 normal subjects undertook different incremental treadmill exercise protocols to explore the relationship between and . An incremental protocol using 1 instead of 3-min stages of exercise resulted in an increase in the to ratio [26.84 (SEM 1.23) vs 31.08 (SEM 1.36) (P < 0.008) for the first stage, 25.24 (SEM 0.86) vs 27.83 (SEM 0.91) (P < 0.005) for the second stage and 23.90 (SEM 0.86) vs 26.34 (SEM 0.81) (P = 0.001) for the third stage]. Voluntary hyperventilation to double the control level of during exercise resulted in an increase in the to slope [from 21.3 (SEM 0.71) for the control run to 35.1 (SEM 1.2) for the hyperventilation run (P < 0.001)]. Prolonged hyperventilation (5 min) during exercise at stage 2 of the Bruce protocol resulted in a continuted elevation of and the slope. A steady state of and metabolic gas exchange can only be said to have been present after at least 3 min of exercise. Voluntary hyperventilation increased the slope of the relationship between and . End-tidal carbon dioxide fell, but remained within the normal range. These results would suggest that a non-carbon dioxide factor may have been responsible for the increase we found in during exercise, and that factors other than increased dead space ventilation can cause an increased ventilation to slope, such as that seen in some pathophysiological conditions, such as chronic heart failure.     

Diffusion-limited gas mixing in the lung and its consequences for transpulmonary gas transport

The ratio of alveolar ventilations of He and SF₆ ( ) was determined in 7 healthy male subjects at rest and at three different levels of exercise on a bicycle ergometer (75, 150 and 225 W). This ratio was calculated from the ratio of the specific ventilations for these gases which were obtained from the decay of the end-tidal partial pressures of He and SF₆ during a simultaneous, multiple-breath washout. In all experiments, for He was larger than for SF₆. On the average, was equal to 1.09, and the mean values of this ratio at rest and at the three levels of exercise were not significantly different. Therefore, the difference in for He and SF₆ increased with increasing work load. Further, we used the mean value obtained for , to calculate the ratio of excretion values (E₁/E₂) for pairs of hypothetical tracer gases with equal blood-gas partition coefficients and with different diffusivities in the gas phase. E₁/E₂ ranged from anity for =0 to about 1.08 for =10. At a given , E₁/E₂ decreased with increasing ventilation-perfusion ratio of the lung. Thus, the difference between the excretion values of light and heavy tracer gases will be most pronounced under rest conditions and for gases that are well soluble in blood.     

Le métabolisme non lié à l'activité musculaire est fonction de {\text{FA}}_{{\text{CO}}_{\text{2}} } et de la température

Summary Metabolic variations as a function of and as a function of temperature are studied in curarized, artificially ventilated cats. Metabolic rate is measured in terms of O₂ uptake and CO₂ production. Measures are taken for variations of 4–7% and for temperatures between 42 and 21°C. The results are presented in the form of graphs. Metabolism decreases when increases and increases when temperature increases. The shape of the curve obtained when values for metabolic rate are plotted as a function of temperature, depends upon the ventilation which acts by determining the magnitude of .     

Potassium activity in cells of isolated perfused cortical thick ascending limbs of rabbit kidney

The Na⁺2Cl^–K⁺ cotransporter in the apical membrane of the cortical thick ascending limb of the Henle's loop (cTAL) of rabbit nephron utilizes the electrochemical gradient for Na⁺ to transport K⁺ and Cl^– against an unfavorable electrochemical gradient from lumen to cell interior. In the present study attempts are made to measure intracellular K⁺ activity ( ) under control conditions and after inhibition of the cotransport system by furosemide (50·10^–6 mol·l^–1). 70 cTAL segments of 55 rabbits were perfused in vitro. Conventional Ling-Gerard and K⁺-selective microelectrodes were used to measure the PD across the basolateral membrane (PD_bl) as well as the PD sensed by the single barrelled K⁺-selective electrode ( ). PD_bl was –64±1 (n=65) mV and +15±1 (n=32) mV under control conditions. The positive value, significantly different from zero, indicates that is higher than predicted for passive distribution. The estimate for obtained from PD_bl and was 113±8 mmol·l^–1. Furosemide lead to the previously reported hyperpolarization of PD_bl by 17±4 (n=13) mV and to a reduction of from 15±1 to 5±1 (n=20) mV. The , obtained from this set of data, was 117±9 mmol·l^–1, and was not different from the control value. The present data indicate that is significantly above Nernst equilibrium under control conditions. The source for this above equilibrium accumulation of K⁺ stems from the carrier mediated uptake of Na⁺2Cl^– and K⁺. Consequently, the electrochemical gradient for K⁺ is rapidly reduced when the carrier is blocked by furosemide. The electrochemical gradient for K⁺, under control conditions, energizes the back leak of K⁺ from cell to lumen. This K⁺ flux is one component responsible for the lumen positive transepithelial PD.Parts of this study have been presented at the 58th Tagung Deutsche Physiologische und Deutsche Pharmakologische Gesellschaft, Mainz 1983; 67th Federation Meeting, Chicago 1983. This study was supported by Deutsche Forschungsgemeinschaft Gr. 480/5-7     

The role of the vagus nerves in the respiratory response to CO2 under hyperoxic conditions

Summary In anesthetized rabbits rebreathing oxygen the respiratory and circulatory responses to increased were determined repeatedly in the same animal before and after inactivation of the vagus nerves by cold blocking and finally sectioning. In some animals responses were also obtained by blocking the vagi during respiration of constant mixtures of CO₂ and O₂. With intact vagi the response curve was, on the average, practically linear up to an increase of the by 27 Torr. Inactivation of the vagi caused a small increase of the resting ventilatory minute volume during the initial breathing of pure oxygen, and a corresponding decrease of the resting . In the range of small increases of the response curve was significantly steepened and shifted to higher ventilatory values by the inactivation. With greater increases, the slope of the response with inactivated vagi was flatter and shifted to lower ventilatory values as compared with intact vagi. These effects were the result of corresponding changes of the response curves for tidal volume and respiratory rate: Inactivation considerably steepened the response at low values of while flattening the response at high values, whereas the curve was only depressed at all stages of hypercapnia. The results were principally the same whether the carotid sinus nerves were intact or sectioned. Vagal inactivation had only little influence on the reactions of systemic blood pressure and heart rate to the increase of . It is concluded that vagal reflexes, possibly from stretch receptors of the lungs, modify the ventilatory efficacy of the central chemosensitive drive of respiration in the rabbit.Supported by grant Wi 165 from the Deutsche Forschungsgemeinschaft.     

The mechanism of the urinary concentrating defect in potassium deficient rats

Summary The mechanism of the defect in urinary concentrating capacity in potassium deficiency was investigated by measuring solute-free water reabsorption ( ) in normal and hypokalemic rats undergoing mannitol diuresis. Since potassium-deficiency markedly lowered glomerular filtration rate (GFR), was examined in normal rats whose GFR had been comparably reduced either acutely by aortic constriction or chronically by feeding a salt- and protein-free diet. By calculating the volume of filtrate delivered to the loop of Henle from the GFR and C _osm it was found that in normal rats was linearly related to volume delivery. At each level of volume delivery to the loop hypokalemic rats formed about half the normal amount of . Decreased solute delivery to the loop of Henle, therefore, cannot be the cause of the concentrating defect in hypokalemia. It is concluded, therefore, that the impaired concentrating capacity in potassium deficiency results from defective sodium transport in the ascending limb of Henle's loop, so that at any level of sodium delivery to the loop less sodium is transported into the medulla and therefore less is generated.

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Zusammenfassung Der Mechanismus der verminderten Harnkonzentrierung bei Kaliummangel wurde anhand der Bestimmung des rückresorbierten freien Wassers ( ) während Mannitoldiurese an normalen und hypokaliämischen Ratten untersucht. Da die glomeruläre Filtration der hypokaliämischen Ratten deutlich eingeschränkt war, wurde bei den normalen Tieren eine ähnliche Reduktion der glomerulären Filtration akut durch Constriction der Aorta und chronisch durch Fütterung einer NaCl- und Protein-freien Diät erreicht.Das in die Henlesche Schleife einströmende Primärharnvolumen wurde aus der glomerulären Filtration und der osmolaren Clearance (Cosm) berechnet. Das Konzentrationsvermögen ( ) erwies sich als lineare Funktion des in die Henlesche Schleife einströmenden Primärharnvolumens. In hypokaliämischen Ratten war das Konzentrationsvermögen ( ) verglichen mit dem in die Henlesche Schleife einströmenden Primärharnvolumen, im ganzen Bereich auf ungefähr die Hälfte eingeschränkt.Daraus wird geschlossen, daß die eingeschränkte Harnkonzentrierung bei Hypokaliämie durch verminderten Natriumtransport im aufsteigenden Schenkel der Henleschen Schleife verursacht wird, und zwar derart, daß von der in die Henlesche Schleife einströmenden Natriummenge ein geringerer Anteil ins Nierenmark transportiert wird und deshalb weniger gebildet werden kann.

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This work was supported in part by a grant from the Dallas Heart Association and in part by a training grant 5 TI HE 5469-04 from the National Institutes of Health, U. S. Public Health Service.

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Work performed as trainee of U. S. Public Health Service, grant 5 TI HE 5469-04.     

Physical fitness of blind and sighted children

Summary Twenty-seven children (age 7–17 years) with varying degrees of blindness but with no other known disorder were assessed for physical fitness. Twenty-seven randomly selected children with normal eyesight were also assessed. Maximum oxygen uptake ( ) was measured directly during a progressive exercise test on a treadmill. There was a significant and substantial reduction in in totally blind children (mean ± standard deviation 35.0±7.5 ml · min^–1 · kg^–1) compared with normal children (45.9±6.6 ml · min^–1 · kg^–1). Partially sighted children had a significant but smaller reduction in . Fitness assessed by a step-test was significantly reduced in the visually impaired children, and skin-fold thickness was also significantly greater in totally blind children.The level of habitual physical activity for each child, as assessed by a questionnaire, correlated with (r=0.53,p<0.0001). Blind children were significantly less active than normal children, and the difference between mean for blind and normal children became non-significant when their different activity levels were taken into account. It is concluded that totally blind children are less fit than other children at least partly because of their lower level of habitual activity.     

A model for studying the distortion of muscle oxygen uptake patterns by circulation parameters

Summary The transmission of muscle oxygen uptake patterns to the pulmonary site is a basically nonlinear process during unsteady state exercise. We were mainly interested in three questions concerning the dynamic relationship between power input and pulmonary output: 1. To what extent can linear system analysis be applied? 2. What is the relative influence of muscle on pulmonary as compared to other parameters such as muscle perfusion kinetics? 3. To what extent does pulmonary reflect muscle ? Investigations were performed by means of a mathematical model including a muscle compartment and two serial, flow-varying time delays. The non-exercising parts of the body were. incorporated as one term for perfusion and one for . Parameters were adjusted so as to represent a reference state of aerobic exercise while monofrequent sinusoidal changes in aerobic metabolism were used as forcing signals. The following answers were derived from the simulations: 1. Non-linear distortions of the signals are negligible provided that analyses are not driven too far into the higher frequency range (periods shorter than about 1 min). 2. Variations of muscle kinetics have greater effects on pulmonary than changes of perfusion kinetics or venous volume. This finding applies irrespective of whether or not pulmonary closely reflects muscle 3. Small differences in the time constants for muscle perfusion and muscle are a major prerequisite if pulmonary , kinetics are to be taken as correct estimates of muscle kinetics. High basal muscle perfusion, small perfusion changes and small venous volumes between muscle and lungs are further factors reducing dynamic distortions of the muscle signal.     

Effects of temperature variation on the discharges of a monosynaptic reflex. Role of simultaneous variation of \textPA\textCO2 {\text{PA}}_{{\text{CO}}_2 }

Summary Decrease of temperature raises the action potential of the monosynaptic reflex of the masseter nerve in curarized cats artificially ventilated at a constant level. This augmentation is due to: specific action of temperature and simultaneous variation of . Indeed, decreasing the temperature in an animal artificially ventilated, when ventilation is constant, involves a decreasing . Interpretation of the stimulus-response curve of the monosynaptic reflex of the masseter nerve allows us to explain the action of decreasing by a rise in motoneuron excitability, and the action of decreasing temperature by a rise in action potential of the motoneurons.With 1 Figure in the Text     

Changes of ventilation and ventilatory response to hypoxia during the menstrual cycle

The relationship between change in hypoxic sensitivity in respiration, defined as increment in ventilation per drop of arterial O₂ saturation , with the phase change from follicular to luteal and those in resting pulmonary ventilation , mean inspiratory flow (V _T/T _I), alveolar partial pressures of CO₂ and O₂ ( and , respectively) and body temperature was studied in 10 women. There was a significant relationship between % increase in hypoxic sensitivity and decrement of resting that occurred in the luteal phase. However, no significant relationships were observed between change in hypoxic sensitivity and those in the remaining parameters studied. The intersubject variation in % increase in resting during the luteal phase was not associated with that in % increase in hypoxic sensitivity. The results indicate that the contribution of increased hypoxic sensitivity to increasing during the luteal phase is variable among subjects. Reasons for the increase in hypoxic sensitivity with hypocapnia are discussed.     

Increase in atrial natriuretic peptide in response to physical exercise

Summary Circulating atrial natriuretic peptide (ANP) level was determined during physical exercise to investigate the correlation between changes in ANP level and heart rate increases.Six subjects exercised at a work level of 75% for 30 min, two also performed two successive exercises at 75% while two more exercised for longer at 55% · Plasma ANP levels and heart rate increased in all the exercising subjects. At the end of the exercise, the ANP level fell immediately, suggesting an immediate reduction in ANP secretion by the heart. Pre-exercise values were reached after 30 min. Successive exercises gave the same heart rate related ANP patterns without previous secretory episodes having any effect. These results lead to the conclusion that ANP intervenes in the cardiovascular adjustments to exercise.     

Influence of heat stress and acclimation on maximal aerobic power

Summary Thirteen male volunteers performed cycle ergometer maximal oxygen uptake ( tests) in moderate (21 C, 30% rh) and hot (49 C, 20% rh) environments, before and after a 9-day heat acclimation program. This program resulted in significantly decreased (P<0.01) final heart rate (24 bt·min^–1) and rectal temperature (0.4 C) from the first to last day of acclimation. The was lower (P<0.01) in the hot environment relative to the moderate environment both before (8%) and after (7%) acclimation with no significant difference (P>0.05) shown for maximal power output (PO max, watts) between environments either before or after acclimation. The was higher (P<0.01) by 4% after acclimation in both environments. Also, PO max was higher (P<0.05) after acclimation in both the moderate (4%) and hot (2%) environments. The reduction in in the hot compared to moderate environment was not related to the difference in core temperature at between moderate and hot trials, nor was it strongly related with aerobic fitness level. These findings indicate that heat stress, per se, reduced the . Further, the reduction in due to heat was not affect be state of heat acclimation, the degree of elevation in core temperature, or level of aerobic fitness.     

Use of oxygen uptake recovery curve to predict peak oxygen uptake in upper body exercise

A group of 18 well-trained white-water kayakers performed maximal upper body exercise in the laboratory and during.a field test. Laboratory direct peak oxygen uptake ( ) values were compared, firstly by a backward extrapolation estimation and secondly by an estimation calculated from measured during the first 20 s of exercise recovery. Direct peak correlated with backward extrapolation (r=0.89), but the results of this study showed that the backward extrapolation method tended to overestimate significantly peak by [0.57 (SD 0.31) 1·min^–1 in the laboratory, and 0.66 (SD 0.33) 1·min^–1 in the field,P<0.001]. The measured during the first 20 s of recovery, whether the exercise was performed in the laboratory or in the field, correlated well with the laboratory direct peak (r=0.92 andr=0.91, respectively). The use of the regression equation obtained from field data _2f20s, that is peak ₂=0.23+1.08 _2f20s, gave an estimated peak ₂, the mean difference of which compared with direct peak was 0.22 (SD 0.13) 1·min^–1. In conclusion, we propose the use of a regression equation to estimate peak from a single sample of the gas expired during the first 20 s of recovery after maximal exercise involving the upper part of the body.