On the edema-preventing effect of the calf muscle pump

During motionless standing an increased hydrostatic pressure leads to increased transcapillary fluid filtration into the interstitial space of the tissues of the lower extremities. The resulting changes in calf volume were measured using a mercury-in-silastic strain gauge. Following a change in body posture from lying to standing or sitting a two-stage change in calf volume was observed. A fast initial filling of the capacitance vessels was followed by a slow but continuous increase in calf volume during motionless standing and sitting with the legs dependent passively. The mean rates of this slow increase were about 0.17%.min-1 during standing and 0.12%.min-1 during sitting, respectively. During cycle ergometer exercise the plethysmographic recordings were highly influenced by movement artifacts. These artifacts, however, were removed from the recordings by low-pass filtering. As a result the slow volume changes, i.e. changes of the extravascular fluid were selected from the recorded signal. Contrary to the increases during standing and sitting the calf volumes of all 30 subjects decreased during cycle ergometer exercise. The mean decrease during 18 min of cycling (2-20 min) was -1.6% at 50 W work load and -1.9% at 100 W, respectively. This difference was statistically significant (p less than or equal to 0.01). The factors which may counteract the development of an interstitial edema, even during quiet standing and sitting, are discussed in detail. During cycling, however, three factors are most likely to contribute to the observed reduction in calf volume: (1) The decrease in venous pressure, which in turn reduces the effective filtration pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calf blood flow and posture: Doppler ultrasound measurements during and after exercise.

To investigate the joint effects of body posture and calf muscle pump, the calf blood flow of eight healthy volunteers was measured with pulsed Doppler equipment during and after 3 min of rhythmic exercise on a calf ergometer in the supine, sitting, and standing postures. Muscle contractions seriously impeded calf blood flow. Consequently, blood flow occurred mainly between contractions and reached a plateau that lasted at least the final 100 s of each exercise series. After exercise the blood flow decreased much faster in the sitting and standing postures than in the supine posture. There was no difference in blood flow between various postures during the same submaximal exercise. However, subjects in the standing posture were able to perform exercise with a higher load than in the supine posture, and blood flow in the standing posture could become twice as high as in the supine posture. We conclude that calf blood flow is regulated according to needs; available perfusion pressure determined maximal blood flow and exercise; and compared with the supine posture, the standing posture and calf muscle pump increase the perfusion pressure.     

Metabolic responses to light arm and leg exercise when sitting

Seven male subjects performed progressive exercises with a light work load on an upper limb or bicycle ergometer in the sitting position. At any comparable work load above zero, arm exercise induced higher oxygen uptake, ventilation, heart rate, oxygen pulse, respiratory rate and tidal volume than leg exercise. At similar levels of VO2 above 0.45 1 X min-1, heart rate and ventilation were higher during arm exercise. A close linear relationship between carbon dioxide output and oxygen uptake was observed during both arm and leg exercises, the slope for arm work being steeper. The ventilatory equivalent for VCO2 (VE/VCO2) gradually decreased during both types of exercise. The ventilatory equivalent for VO2(VE/VO2) remained constant (arm) while it rose (leg) to a peak at 9.8 W and then gradually decreased. Ventilation in relation to tidal volume had a linear relationship with leg exercise, but became curvilinear with arm exercise after tidal volume exceeded 1100 ml. The observed differences in response between arm and leg exercises at a given work load appear to be influenced by differences in sympathetic outflow due to the greater level of static contraction of the relatively small muscle groups required by arm exercise.     

Adaptation of human left ventricular volumes to the onset of supine exercise

The purpose of this study was to measure the changes and rates of adaptation of left ventricular volumes at the onset of exercise. Eight asymptomatic subjects, in whom intramyocardial markers had been implanted 3-6 years previously during aortocoronary bypass surgery, exercised in the supine position at a constant workload of 73.6 W for 5 min. Six also exercised first at 16.4 W, and then against a workload which progressively increased by 8.2 W every 15 s. Cardiac volumes were measured by computer assisted analysis of the motion of the implanted markers. In the constant workload test, cardiac output increased rapidly from 5.7 +/- 1 min-1 to 10.3 +/- 1.9 1 min-1 by 2 min and then increased more slowly to 10.8 +/- 2.0 1 min-1 by 5 min. The cardiac output increase was mainly due to an increase in heart rate from 68 +/- 12 beats min-1 to 120 +/- 16 beats min-1 with minimal changes in stroke volume. The time constant for the early increase in cardiac output was 45s and for heart rate, 35s. With progressively increasing workloads, there was an almost linear increase of heart rate and cardiac output, but these increased at a slower rate than during the early phase of the constant load exercise test. In conclusion: rapid changes in cardiac output during supine exercise were produced by changes in heart rate; changes in stroke volume provided minor adjustments to cardiac output; the end-diastolic volume was almost constant.     

Limb vs trunk sweat gland recruitment patterns during exercise in humans

The purpose of this study was to examine the sweat gland recruitment pattern, on multiple trunk and limb sites, during exercise. Nineteen male volunteers performed 30 min of exercise on a cycle ergometer at approx. 25, 50 and 75% of their maximal oxygen uptake. The number of active sweat glands (per cm(2)) was determined immediately following each exercise bout at the following six sites: left triceps, chest, back, forearm, thigh and calf. The data showed that increases in rectal temperature during exercise resulted in a linear increase in the absolute number of active sweat glands recruited at all six sites (r=0.60-0.80). However, on a percentage basis, the limb sites increased proportionally more (300-600% increase) than the trunk sites (100-200% increase) with increases in rectal temperature. These data suggest that the absolute number of sweat glands recruited, on both the trunk and the limbs, increases in a linear manner with increases in rectal temperature during exercise. However, on a proportional basis, sweat gland recruitment on the limbs is greater than that found on the trunk during progressive exercise.     

Total power output generated during dynamic knee extensor exercise at different contraction frequencies.

A novel approach has been developed for the quantification of total mechanical power output produced by an isolated, well-defined muscle group during dynamic exercise in humans at different contraction frequencies. The calculation of total power output comprises the external power delivered to the ergometer (i.e., the external power output setting of the ergometer) and the "internal" power generated to overcome inertial and gravitational forces related to movement of the lower limb. Total power output was determined at contraction frequencies of 60 and 100 rpm. At 60 rpm, the internal power was 18+/- 1 W (range: 16-19 W) at external power outputs that ranged between 0 and 50 W. This was less (P<0.05) than the internal power of 33+/-2 W (27-38 W) at 100 rpm at 0-50 W. Moreover, at 100 rpm, internal power was lower (P<0.05) at the higher external power outputs. Pulmonary oxygen uptake was observed to be greater (P<0.05) at 100 than at 60 rpm at comparable total power outputs, suggesting that mechanical efficiency is lower at 100 rpm. Thus a method was developed that allowed accurate determination of the total power output during exercise generated by an isolated muscle group at different contraction frequencies.     

A study of physical demands in riding

Thirteen experienced riders and three elite riders underwent bicycle ergometer tests at submaximal and maximal workloads. Oxygen uptake, pulmonary ventilation and heart rate were also studied during riding at a walk, a trot and a canter. The mean maximal oxygen uptake of the experienced riders in the ergometer test (2.71 . min-1) was superior to the average maximal oxygen uptake of other groups of the same age and sex. The average oxygen uptake of the experienced riders in trot sitting was 1.701 . min-1, trot rising 1.681 . min-1 and in canter 1.801 . min-1. The experienced riders used at least 60% of their maximal aerobic power in trot and canter, which is an exercise intensity that may induce some training effect. Two elite riders consistently had lower oxygen uptakes in riding than the other riders. The heart rate -- oxygen uptake relationships in riding and in the ergometer tests were similar, except during trot sitting when the heart rate tended to be higher, indicating a larger share of static muscle contraction in this gait. Static muscle strength was measured in nine riders and seven non-riders. Six muscle groups were investigated, but no significant difference in muscle strength could be demonstrated between riders and controls.     

Hemodynamic responses during prolonged sitting

Eight young men (group A) underwent 5 h of quiet sitting, preceded by 30 min of recumbency, 20 min of standing, and 20 s of walking, and five other young men (group B) underwent 70 min of sitting, preceded by recumbency only, to determine the effects of prolonged sitting and previous posture on hemodynamic responses (measured by impedance plethysmography). Group A showed more calf blood pooling and a decrease in thigh blood flow during sitting in comparison with the control group, but after 1 h of sitting hemodynamic responses of the two groups were similar. Sitting for 5 h (1st vs. 5th h) resulted in an increase in calf venous pooling (17%) and a decrease in calf BF (13%), a reduction in gravitational pooling in the thigh (corresponding to increased pooling in the calf), increases in diastolic and mean arterial pressures (6 and 7.3 mmHg, respectively), and minor changes in heart rate, stroke volume, and cardiac output. The results show that it is necessary to sit for 1 h before hemodynamic responses can be assessed in this position, regardless of the posture maintained previously. The main effect of prolonged sitting is pooling in the calf, which is compensated for by an increase in peripheral resistance.     

Effects of standing cycling and the use of toe stirrups on maximal oxygen uptake

Twenty-eight subjects (6 normal men, 14 distance runners, and 8 rowers) were tested for maximal oxygen uptake (VO2max) and associated physiological measures during bicycle ergometer exercise with toe stirrups while standing (BEts) and during treadmill exercise (TM). Correlation between BEts VO2max and TM VO2max was high (r = 0.901, p less than 0.05). No significant difference existed between the two VO2max values (60.3 +/- 8.9 vs. 60.5 +/- 9.7 ml.kg-1.min-1; n = 28). No differences were found even when three different subgroups were separately compared. It is concluded that the higher VO2max elicited during BEts as compared with normal sitting cycling may be attributed to the increased muscle blood flow and/or involvement of a larger muscle mass, the latter being partly evidenced by the observation of greater electromyographic activity during BEts.     

Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake

It is not known whether the diameter of peripheral conduit arteries may impose a limitation on muscle blood flow and oxygen uptake at peak effort in humans, and it is not clear whether these arteries are dimensioned in relation to the tissue volume they supply or, rather, to the type and intensity of muscular activity. In this study, eight humans, with a peak pulmonary oxygen uptake of 3.90 +/- 0.31 (range 2.29-5.03) l/min during ergometer cycle exercise, performed one-legged dynamic knee extensor exercise up to peak effort at 68 +/- 7 W (range 55-100 W). Peak values for knee extensor blood flow (thermodilution) and oxygen uptake of 6.06 +/- 0.74 (range 4.75-9.52) l/min and 874 +/- 124 (range 590-1,521) ml/min, respectively, were achieved. Pulmonary oxygen uptake reached a peak of 1.72 +/- 0.19 (range 1.54-2.33) l/min. Diameters of common and profunda femoral arteries determined by ultrasound Doppler were 10.6 +/- 0.4 (range 8.2-12.7) and 6.0 +/- 0.4 (range 4.5-8.0) mm, respectively. Thigh and quadriceps muscle volume measured by computer tomography were 10.06 +/- 0.66 (range 6.18-10.95) and 2.36 +/- 0.19 (range 1.31-3.27) liters, respectively. The common femoral artery diameter, but not that of the profunda branch, correlated with the thigh volume and quadriceps muscle mass. There were no relationships between either of the diameters and the absolute or muscle mass-related resting and peak values of blood flow and oxygen uptake, peak pulmonary oxygen uptake, or peak power output during knee extensor exercise. However, common femoral artery diameter correlated to peak pulmonary oxygen uptake during ergometer cycle exercise. In conclusion, common and profunda femoral artery diameters are sufficient to ensure delivery to the quadriceps muscle. However, the common branch may impose a limitation during ergometer cycle exercise.     

Effect of alcohol on perceived exertion in relation to heart rate and blood lactate

The purpose of the study was to determine whether the perception of exertion is affected by alcohol during physical performance and whether altered self-rating of exertion is the result of an altered perception per se or of an altered physical capacity to perform work. Ten healthy men participated. Each subject was his own control and received an alcohol dose corresponding to 1 g.kg-1 body mass in 40% solution in the experimental session. The exercise test was performed on a cycle ergometer with an initial intensity of 50 W which was increased stepwise by 50 W at 4-min intervals up to near-maximal. The rating of perceived exertion (RPE) did not differ between alcohol and control sessions. Alcohol induced a significant increase in heart rate during exercise at 50 W (delta x = 8 beats.min-1) and at 100 W (delta x = 10 beats.min-1), while the change at higher intensities was insignificant. The systolic blood pressure and the blood lactate concentration were not significantly changed by alcohol. It is concluded that a moderate dose of alcohol does not alter RPE during physical exercise either per se or secondarily to an altered physical capacity to perform work.     

Calf blood flow and posture: Doppler ultrasound calibrated by plethysmography.

A procedure was developed that enables measurement of rapid variations in calf blood flow during voluntary rhythmic contraction of the calf muscles in supine, sitting, and standing positions. During the exercise, maximum blood velocity is measured by Doppler ultrasound equipment in the popliteal artery. The Doppler signals are calibrated by plethysmography to enable calculation of blood flow during exercise in ml.100 ml-1.min-1. Knowledge of the cross-sectional area of the vessel and the angle of insonation is not required in this procedure. Evaluation of the calibration method with 10 healthy volunteers showed that for each subject a new calibration was necessary after a change in posture; the relationship between the blood flow and the maximum Doppler frequency averaged over one heart cycle was linear for each calibration.     

Reduction in extracellular muscle volume increases heart rate and blood pressure response to isometric exercise

To investigate the effect of local dehydration on heart rate and blood pressure during static exercise, six healthy male subjects performed exercise of the calf muscles with different extracellular volumes of the working muscles. Exercise consisted of 5 min of static calf muscle contractions at about 10% of maximal voluntary contraction. The body position during exercise was identical in all tests, i.e. supine with the knee joint 90 degrees flexed. During a 25-min pre-exercise period three different protocols were employed to manipulate the calf volume. In test A the subjects rested in the exercise position; in test B the body position was the same as in A but calf volumes were increased by venous congestion [cuffs inflated to 10.67 kPa (80 mmHg)]; in test C the calf volumes were decreased by lifting the calves about 40 cm above heart level with the subjects supine. To clamp the changed calf volumes in tests B and C, cuffs were inflated to 300 mmHg 5 min before the onset of exercise. This occlusion was maintained for 1 min after the termination of exercise. Compared to tests A and B, the reduced volume of test C led to significant increases in heart rate and blood pressure during exercise. Oxygen uptake did not exceed resting levels in tests B and C until the cuffs were deflated, indicating that only calf muscles contributed to the neurogenic peripheral drive. It is concluded that extracellular muscle volume plays a significant role in adjusting heart rate and blood pressure during static exercise.     

Human diaphragmatic EMG: changes with lung volume and posture during supramaximal phrenic stimulation

If esophageal and chest wall recordings of diaphragmatic electromyographic activity (EMG) accurately reflect neural drive to this muscle, then compound muscle action potentials (CMAPs) produced by supramaximal stimulation of the phrenic nerve should not alter with changes in diaphragmatic position. Maximal CMAPs were therefore recorded 1) during changes in lung volume from near residual volume to near total lung capacity, 2) during isovolume maneuvers at different lung volumes, and 3) while subjects were lying, sitting, and standing. The areas of maximal CMAPs recorded with the gastroesophageal catheter increased 5.1 +/- 3.6 times (mean +/- SD) between these volumes, increased 2.4 +/- 1.3 times as the diaphragm descended during an isovolume maneuver (at functional residual capacity), and increased 4.4 +/- 2.4 times between the lying and standing positions. Because the stimuli were supramaximal, these changes in EMG reflect changes in the relationship between the esophageal electrodes and the diaphragmatic muscle fibers. Artifactual changes were also documented for surface electrodes on the chest wall. Because of these positional changes in maximal CMAPs, previous studies, which used integrated diaphragmatic EMG to document "reflex" changes in neural drive, should be reevaluated.     

Endurance training slows down the kinetics of heart rate increase in the transition from moderate to heavier submaximal exercise intensities

To find out whether endurance training influences the kinetics of the increases in heart rate (fc) during exercise driven by the sympathetic nervous system, the changes in the rate of fc adjustment to step increments in exercise intensities from 100 to 150 W were followed in seven healthy, previously sedentary men, subjected to 10-week training. The training programme consisted of 30-min cycle exercise at 50%-70% of maximal oxygen uptake (VO2max) three times a week. Every week during the first 5 weeks of training, and then after the 10th week the subjects underwent the submaximal three-stage exercise test (50, 100 and 150 W) with continuous fc recording. At the completion of the training programme, the subjects' VO2max had increased significantly (39.2 ml.min-1.kg-1, SD 4.7 vs 46 ml.min-1.kg-1, SD 5.6) and the steady-state fc at rest and at all submaximal intensities were significantly reduced. The greatest decrease in steady-state fc was found at 150 W (146 beats.min-1, SD 10 vs 169 beats.min-1, SD 9) but the difference between the steady-state fc at 150 W and that at 100 W (delta fc) did not decrease significantly (26 beats.min-1, SD 7 vs 32 beats.min-1, SD 6). The time constant (tau) of the fc increase from the steady-state at 100 W to steady-state at 150 W increased during training from 99.4 s, SD 6.6 to 123.7 s, SD 22.7 (P less than 0.01) and the acceleration index (A = 0.63.delta fc.tau-1) decreased from 0.20 beats.min-1.s-1, SD 0.05 to 0.14 beats.min-1.s-1, SD 0.04 (P less than 0.02). The major part of the changes in tau and A occurred during the first 4 weeks of training. It was concluded that heart acceleration following incremental exercise intensities slowed down in the early phase of endurance training, most probably due to diminished sympathetic activation.     

Thermoregulatory responses to upper body exercise

The purpose of this study was to compare thermoregulatory responses between upper body and lower body exercise. Nine male subjects performed 60 min of arm crank (AC) and cycle (CY) exercise at the same absolute intensity (oxygen uptake = 1.61 X min-1) and at the same relative intensity (60% of ergometer specific peak oxygen uptake) in a temperate (24 degrees C, 20% rh) environment. During the absolute intensity experiments, rectal temperature and sweating rate responses were essentially the same for both modes of exercise. In addition, no differences were found for chest, back, arm, or thigh skin temperatures, but calf skin temperature was significantly (P less than 0.05) lower during arm crank than cycle exercise. During the relative intensity experiments, thermoregulatory responses were lower during arm crank than cycle exercise. In addition, we found no difference between esophageal and rectal temperature values elicited by arm crank exercise. These results indicate that the examined thermoregulatory responses are independent of the skeletal muscle mass employed and dependent upon the absolute metabolic intensity.     

Effects of 8-week in-season upper and lower limb heavy resistance training on the peak power, throwing velocity, and sprint performance of elite male handball players

The aims of this study were to test the potential of in-season heavy upper and lower limb strength training to enhance peak power output (Wpeak), vertical jump, and handball related field performance in elite male handball players who were apparently already well trained, and to assess any adverse effects on sprint velocity. Twenty-four competitors were divided randomly between a heavy resistance (HR) group (age 20 ± 0.7 years) and a control group (C; age 20 ± 0.1 years). Resistance training sessions were performed twice a week for 8 weeks. Performance was assessed before and after conditioning. Peak power (W(peak)) was determined by cycle ergometer; vertical squat jump (SJ) and countermovement jump (CMJ); video analyses assessed velocities during the first step (V(1S)), the first 5 m (V(5m)), and between 25 and 30 m (V(peak)) of a 30-m sprint. Upper limb bench press and pull-over exercises and lower limb back half squats were performed to 1-repetition maximum (1RM). Upper limb, leg, and thigh muscle volumes and mean thigh cross-sectional area (CSA) were assessed by anthropometry. W(peak) (W) for both limbs (p < 0.001), vertical jump height (p < 0.01 for both SJ and CMJ), 1RM (p < 0.001 for both upper and lower limbs) and sprint velocities (p < 0.01 for V(1S) and V(5m); p < 0.001 for V(peak)) improved in the HR group. Upper body, leg, and thigh muscle volumes and thigh CSA also increased significantly after strength training. We conclude that in-season biweekly heavy back half-squat, pull-over, and bench-press exercises can be commended to elite male handball players as improving many measures of handball-related performance without adverse effects upon speed of movement.     

Postural cardiovascular reflexes: comparison of responses of forearm and calf resistance vessels

Simultaneous measurements were made of changes in vascular resistance in the forearm and calf in response to moving from supine to sitting or to head-down tilt. The subjects were healthy male volunteers, 21-63 yr. Blood flows were measured by venous occlusion plethysmography using mercury-in-Silastic strain-gauges. The gauges were maintained at the same level relative to the heart during the postural changes. Arterial blood pressure was measured by auscultation; heart rate was counted from the plethysmograms. Changing from supine to sitting caused a decrease in forearm blood flow from 4.13 +/- 0.14 to 2.16 +/- 0.19 ml.100 ml-1.min-1. Corresponding calf flows were 4.21 +/- 0.32 and 4.40 +/- 0.59 ml.100 ml-1.min-1. There was no change in mean arterial blood pressure, and heart rate increased by 8.0 +/- 1.5 beats/min. Arrest of the circulation of both legs with occlusion cuffs on the thighs before sitting, to prevent pooling of blood in them, reduced the degree of forearm vasoconstriction. Neck suction (40 Torr) during sitting, to oppose the decrease in transmural pressure at the carotid sinuses, inhibited the vasoconstriction. During a 30 degrees head-down tilt, there was a dilatation of forearm but not of calf resistance vessels. A Valsalva maneuver caused a similar constriction of both vascular beds. Thus, when changes in vascular resistance in forearm and calf are compared, the major reflex adjustments to changes in posture take place in the forearm.     

Ventilatory and gas exchange responses under spontaneous and fixed breathing modes during arm exercise

To evaluate the difference of ventilatory and gas exchange response differences between arm and leg exercise, six healthy young men underwent ramp exercise testing at a rate of 15 W.min-1 on a cycle ergometer separately under either spontaneous (SPNT) or fixed (FIX) breathing modes, respectively. Controlled breathing was defined as a breathing frequency (fb; 30 breaths.min-1) which was neither equal to, nor a multiple of, cranking frequency (50 rev.min-1) to prevent coupling of locomotion and respiratory movement, i.e., so-called locomotor-respiratory coupling (LRC). Breath-by-breath oxygen uptake (VO2), ventilation (VE), CO2 output (VCO2), tidal volume (VT), fb and end-tidal PCO2 (PETCO2) were determined using a computerized metabolic cart. Arm exercise engendered a higher level of VO2 at each work rate than leg exercise under both FIX and SPNT conditions. However, FIX did not notably affect the VO2 response during either arm or leg exercise at each work rate compared to SPNT. During SPNT a significantly higher fb and lower PETCO2 during arm exercise was found compared with leg exercise up to a fb of 30 breaths.min-1 while VE and VT were nearly the same. During fixed breathing when fb was fixed at a higher rate than during SPNT, a significantly lower PETCO2 was observed during both exercise modes. These results suggest that: 1) FIX breathing does not affect the VO2 response during either arm or leg exercise even when non-synchronization between limb locomotion movement and breathing rate was adopted; 2) at a fb of 30 breaths.min-1 FIX breathing induced a hyperventilation resulting in a lower PETCO2 which was not associated with the metabolic rate during either arm or leg exercise, showing that VE during only leg exercise under the FIX condition was significantly higher than under the SPNT condition.     

Effect of saline infusion during exercise on thermal and circulatory regulations

To quantify the effect of an acute increase in plasma volume (PV) on forearm blood flow (FBF), heart rate (HR), and esophageal temperature (Tes) during exercise, we studied six male volunteers who exercised on a cycle ergometer at 60% of maximal aerobic power for 50 min in a warm [(W), 30 degrees C, less than 30% relative humidity (rh)] or cool environment [(C), 22 degrees C, less than 30% rh] with isotonic saline infusion [Inf(+)] or without infusion [Inf(-)]. The infusion was performed at a constant rate of 0.29 ml.kg body wt-1.min-1 for 20-50 min of exercise to mimic fluid intake during exercise. PV decreased by approximately 5 ml/kg body wt within the first 10 min of exercise in all protocols. Therefore, PV in Inf(-) was maintained at the same reduced level by 50 min of exercise in both ambient temperatures, whereas PV in Inf(+) increased toward the preexercise level and recovered approximately 4.5 ml/kg body wt by 50 min in both temperatures. The restoration of PV during exercise suppressed the HR increase by 6 beats/min at 50 min of exercise in W; however, infusion had no effect on HR in C. In W, FBF in Inf(+) continued to increase linearly as Tes rose to 38.1 degrees C by the end of exercise, whereas FBF in Inf(-) plateaued when Tes reached approximately 37.7 degrees C. The infusion in C had only a minor effect on FBF.(ABSTRACT TRUNCATED AT 250 WORDS)