Role of brain IL-1beta on fatigue after exercise-induced muscle damage

Brain cytokines, induced by various inflammatory challenges, have been linked to sickness behaviors, including fatigue. However, the relationship between brain cytokines and fatigue after exercise is not well understood. Delayed recovery of running performance after muscle-damaging downhill running is associated with increased brain IL-1beta concentration compared with uphill running. However, there has been no systematic evaluation of the direct effect of brain IL-1beta on running performance after exercise-induced muscle damage. This study examined the specific role of brain IL-1beta on running performance (either treadmill or wheel running) after uphill and downhill running by manipulating brain IL-1beta activity via intracerebroventricular injection of either IL-1 receptor antagonist (ra; downhill runners) or IL-1beta (uphill runners). Male C57BL/6 mice were assigned to the following groups: uphill-saline, uphill-IL-1beta, downhill-saline, or downhill-IL-1ra. Mice initially ran on a motor-driven treadmill at 22 m/min and -14% or +14% grade for 150 min. After the run, at 8 h (wheel cage) or 22 h (treadmill), uphill mice received intracerebroventricular injections of IL-1beta (900 pg in 2 microl saline) or saline (2 microl), whereas downhill runners received IL-1ra (1.8 microg in 2 microl saline) or saline (2 microl). Later (2 h), running performance was measured (wheel running activity and treadmill run to fatigue). Injection of IL-1beta significantly decreased wheel running activity in uphill runners (P<0.01), whereas IL-1ra improved wheel running in downhill runners (P<0.05). Similarly, IL-1beta decreased and Il-1ra increased run time to fatigue in the uphill and downhill runners, respectively (P<0.01). These results support the hypothesis that increased brain IL-1beta plays an important role in fatigue after muscle-damaging exercise.     

Metabolism of rats running up and down an incline

The purpose of these experiments was to determine oxygen consumption (VO2) in rats as a function of treadmill speed (10, 20, 30, 40, and 50 m . min-1) as they ran on the level and up and down a 16 degree (17.8%) incline. The slopes of the regression lines relating VO2 (ml O2 . kg-1 . min-1) to running speed (m . min-1) were linear for all three inclines. The regression slope for uphill runners (y = 1.25x + 47.7) was greater than the regression slopes for level (y = 0.88x + 41.2) (P less than 0.025) or downhill (y = 0.68x + 39.7) (P less than 0.005) runners, and the regression slope for level runners was greater than that for downhill runners (P less than 0.10). All VO2 measurements were submaximal. In conclusion, incline has a significant effect on the metabolism of rats running on a motor-driven treadmill.     

Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage

Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness, and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investigated for its anti-inflammatory activity and may offset some of the damage and functional deficits associated with downhill running. This study examined the effects of curcumin on inflammation and recovery of running performance following downhill running in mice. Male mice were assigned to downhill placebo (Down-Plac), downhill curcumin (Down-Cur), uphill placebo (Up-Plac), or uphill curcumin (Up-Cur) groups and run on a treadmill at 22 m/min at -14% or +14% grade, for 150 min. At 48 h or 72 h after the up/downhill run, mice (experiment 1) underwent a treadmill performance run to fatigue. Another subset of mice was placed in voluntary activity wheel cages following the up/downhill run (experiment 2) and their voluntary activity (distance, time and peak speed) was recorded. Additional mice (experiment 3) were killed at 24 h and 48 h following the up/downhill run, and the soleus muscle was harvested for analysis of inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and plasma was collected for creatine kinase analysis. Downhill running decreased both treadmill run time to fatigue (48 h and 72 h) and voluntary activity (24 h) (P < 0.05), and curcumin feedings offset these effects on running performance. Downhill running was also associated with an increase in inflammatory cytokines (24 h and 48 h) and creatine kinase (24 h) (P < 0.05) that were blunted by curcumin feedings. These results support the hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage.     

Electromyographic correlates of the transition from aerobic to anaerobic metabolism in treadmill running

This study analysed the changes in electromyographic (EMG) activity of the vastus lateralis, biceps femoris and gastrocnemius muscles during incremental treadmill running. The changes in EMG were related to the lactate and ventilatory thresholds. Ten trained subjects participated in the study. Minute ventilation, oxygen consumption, carbon dioxide expired and the fraction of oxygen in the expired gas were recorded continuously. Venous blood samples were collected at each exercise intensity and analysed for lactate concentration. The EMG were recorded at the end of each exercise intensity using surface electrodes. The EMG were quantified through integration (iEMG) and by calculating the mean power frequency (MPF). The iEMG measurements were characterized by a breakpoint in the vastus lateralis and/or gastrocnemius muscles in eight of the subjects tested. However, the results indicated that blood lactate concentrations had already begun to increase in a nonlinear fashion before the iEMG breakpoint had been surpassed. Consequently, the occurence of the lactate threshold cannot be attributed solely to the change in motor unit recruitment or rate coding patterns demonstrated by the iEMG breakpoint. The ventilatory threshold was shown to be a far more reliable and convenient noninvasive predictor of the lactate threshold in comparison with EMG techniques. In conclusion, the EMG measurements used in this study (i.e. iEMG and MPF) were not considered to be viable noninvasive determinants of the aerobic-anaerobic transition phase in treadmill running.     

Ground reaction forces during downhill and uphill running

We investigated the normal and parallel ground reaction forces during downhill and uphill running. Our rationale was that these force data would aid in the understanding of hill running injuries and energetics. Based on a simple spring-mass model, we hypothesized that the normal force peaks, both impact and active, would increase during downhill running and decrease during uphill running. We anticipated that the parallel braking force peaks would increase during downhill running and the parallel propulsive force peaks would increase during uphill running. But, we could not predict the magnitude of these changes. Five male and five female subjects ran at 3m/s on a force treadmill mounted on the level and on 3 degrees, 6 degrees, and 9 degrees wedges. During downhill running, normal impact force peaks and parallel braking force peaks were larger compared to the level. At -9 degrees, the normal impact force peaks increased by 54%, and the parallel braking force peaks increased by 73%. During uphill running, normal impact force peaks were smaller and parallel propulsive force peaks were larger compared to the level. At +9 degrees, normal impact force peaks were absent, and parallel propulsive peaks increased by 75%. Neither downhill nor uphill running affected normal active force peaks. Combined with previous biomechanics studies, our normal impact force data suggest that downhill running substantially increases the probability of overuse running injury. Our parallel force data provide insight into past energetic studies, which show that the metabolic cost increases during downhill running at steep angles.     

Relationship between muscle fatigue and oxygen uptake during cycle ergometer exercise with different ramp slope increments.

The surface electromyogram (EMG) from active muscle and oxygen uptake (VO2) were studied simultaneously to examine changes of motor unit (MU) activity during exercise tests with different ramp increments. Six male subjects performed four exhausting cycle exercises with different ramp slopes of 10, 20, 30 and 40 W.min-1 on different days. The EMG signals taken from the vastus lateralis muscle were stored on a digital data recorder and converted to obtain the integrated EMG (iEMG). The VO2 was measured, with 20-s intervals, by the mixing chamber method. A non-linear increase in iEMG against work load was observed for each exercise in all subjects. The break point of the linear relationship of iEMG was determined by the crossing point of the two regression lines (iEMGbp). Significant differences were obtained in the exercise intensities corresponding to maximal oxygen uptake (VO2max) and the iEMGbp between 10 and 30, and 10 and 40 W.min-1 ramp exercises (P < 0.05). However, no significant differences were obtained in VO2max and VO2 corresponding to the iEMGbp during the four ramp exercises. With respect to the relationship between VO2 and exercise intensity during the ramp increments, the VO2-exercise intensity slope showed significant differences only for the upper half (i.e. above iEMGbp). These results demonstrated that the VO2max and VO2 at which a nonlinear increase in iEMG was observed were not varied by the change of ramp slopes but by the exercise intensity corresponding to VO2max and the iEMGbp was varied by the change of ramp slopes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acoustic myography reflects force changes during dynamic concentric and eccentric contractions of the human biceps brachii muscle.

The relationship between acoustic myography (AMG), electromyography (EMG) and force during submaximal dynamic contractions was examined in the biceps brachii muscles of eight healthy males (aged 17-26 years). Different weights were lifted and lowered at a constant speed, using a wall pulley system, to perform concentric and eccentric contractions, respectively. Integrated AMG (iAMG) and integrated EMG (iEMG) activity both increased linearly with force during concentric (iAMG r = 0.94; iEMG r = 0.99) and eccentric (iAMG r = 0.90; iEMG r = 0.94) contractions. The slopes of the concentric regression lines were significantly different from the eccentric slopes (P less than 0.01) for both iAMG and iEMG with concentric contractions showing greater levels of activity. The results indicated that AMG can be used to detect changes in force during dynamic contractions which has important implications for the use of AMG in rehabilitation. The differences in iAMG activity between concentric and eccentric contractions are discussed in relationship to the origin of the AMG signal.     

Energy cost of walking and running at extreme uphill and downhill slopes.

The costs of walking (Cw) and running (Cr) were measured on 10 runners on a treadmill inclined between -0.45 to +0.45 at different speeds. The minimum Cw was 1.64 +/- 0.50 J. kg(-1). m(-1) at a 1.0 +/- 0.3 m/s speed on the level. It increased on positive slopes, attained 17.33 +/- 1.11 J. kg(-1). m(-1) at +0.45, and was reduced to 0.81 +/- 0.37 J. kg(-1). m(-1) at -0.10. At steeper slopes, it increased to reach 3.46 +/- 0.95 J. kg(-1). m(-1) at -0.45. Cr was 3.40 +/- 0.24 J. kg(-1). m(-1) on the level, independent of speed. It increased on positive slopes, attained 18.93 +/- 1.74 J. kg(-1). m(-1) at +0.45, and was reduced to 1.73 +/- 0.36 J. kg(-1). m(-1) at -0.20. At steeper slopes, it increased to reach 3.92 +/- 0.81 J. kg(-1). m(-1) at -0.45. The mechanical efficiencies of walking and running above +0.15 and below -0.15 attained those of concentric and eccentric muscular contraction, respectively. The optimum gradients for mountain paths approximated 0.20-0.30 for both gaits. Downhill, Cr was some 40% lower than reported in the literature for sedentary subjects. The estimated maximum running speeds on positive gradients corresponded to those adopted in uphill races; on negative gradients they were well above those attained in downhill competitions.     

Magnetic resonance imaging and electromyography as indexes of muscle function.

Electromyography (EMG) is commonly used to determine the electrical activity of skeletal muscle during contraction. To date, independent verification of the relationship between muscle use and EMG has not been provided. It has recently been shown that relaxation- (e.g., T2) weighted magnetic resonance images (MRI) of skeletal muscle demonstrate exercise-induced contrast enhancement that is graded with exercise intensity. This study was conducted to test the hypothesis that exercise-induced magnetic resonance (MR) contrast shifts would relate to EMG amplitude if both measures reflect muscle use during exercise. Both MRI and EMG data were collected for separate eccentric (ECC) and concentric (CON) exercise of increasing intensity to take advantage of the fact that the rate of increase and amplitude of EMG activity are markedly greater for CON muscle actions. Seven subjects 30 +/- 2 (SE) yr old performed five sets of 10 CON or ECC arm curls with each of four resistances representing 40, 60, 80, and 100% of their 10 repetition maximum for CON curls. There was 1.5 min between sets and 30 min between bouts (5 sets of 10 actions at each relative resistance). Multiple echo, transaxial T2-weighted MR images (1.5 T, TR/TE 2,000/30) were collected from a 7-cm region in the middle of the arm before exercise and immediately after each bout. Surface EMG signals were collected from both heads of the biceps brachii and the long head of the triceps brachii muscles. CON and ECC actions resulted in increased integrated EMG (IEMG) and T2 values that were strongly related (r = 0.99, P < 0.05) with relative resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Downhill running: a model of exercise hyperemia in the rat spinotrapezius muscle.

To utilize the rat spinotrapezius muscle as a model to investigate the microcirculatory consequences of exercise training, it is necessary to design an exercise protocol that recruits this muscle. There is evidence that the spinotrapezius is derecruited during standard treadmill exercise protocols performed on the uphill treadmill (i.e., 6 degrees incline). This investigation tested the hypothesis that downhill running would effectively recruit the spinotrapezius muscle as assessed by the presence of an exercise hyperemia response. We used radioactive 15-microm microspheres to determine blood flows in the spinotrapezius and selected hindlimb muscles of female Sprague-Dawley rats at rest and during downhill (i.e., -14 degrees incline; 331 +/- 5 g body wt, n = 7) and level (i.e., 0 degrees incline; 320 +/- 11 g body wt, n = 5) running at 30 m/min. Both level and downhill exercise increased blood flow to all hindlimb muscles (P < 0.01). However, in marked contrast to the absence of a hyperemic response to level running, blood flow to the spinotrapezius muscle increased from 26 +/- 6 ml.min(-1).100 g(-1) at rest to 69 +/- 8 ml.min(-1).100 g(-1) during downhill running (P < 0.01). These findings indicate that downhill running represents an exercise paradigm that recruits the spinotrapezius muscle and thereby constitutes a tenable physiological model for investigating the adaptations induced by exercise training (i.e., the mechanisms of altered microcirculatory control by transmission light microscopy).     

Evaluation of human dynamic contraction by phonomyography.

Phonomyogram (PMG, or acoustic myogram) is known to increase with force in isometric contractions. We investigated this relationship for dynamic contractions against different inertias. PMG and surface electromyogram (EMG) from biceps brachii and brachioradialis muscles were simultaneously recorded with the angular acceleration of elbow flexions. These were self-initiated movements (30 degrees) toward a fixed target and performed against two different inertias. PMG and EMG were integrated from the onset of the signal to the end of the acceleration phase. Phono- and electromechanical delays were also measured. For integrated EMG (iEMG), there was a linear relationship between integrated PMG (iPMG) and force, the slope of which did not depend on inertia. There was also a linear relationship between iPMG or iEMG and angular acceleration, with a higher slope for the highest inertia condition. There was also a family of linear relationships between iPMG or iEMG and angular acceleration, and their slopes depended on inertia. Measurements of the phono- and electromechanical delays showed that onset of PMG followed that of EMG but preceded onset of acceleration. It is suggested that PMG expresses tension of the underlying muscle contractile elements. Given the simplicity of the PMG method, we conclude that PMG allows convenient evaluation of muscle tension during human dynamic contraction.     

Effect of training on skeletal muscle injury from downhill running in rats

Experiments were conducted to test the hypothesis that injury to skeletal muscle in rats resulting from prolonged downhill running is prevented to a greater extent by prior downhill training than by either uphill or level training. Changes in plasma creatine phosphokinase (CPK) activity and glucose-6-phosphate dehydrogenase (G-6-PDase) activity in the soleus (S), vastus intermedius (VI), and medial head of triceps brachii (TM) muscles were evaluated as markers of muscle injury 48 h after 90 min of intermittent downhill running (16 m . min -1). Prior to this acute downhill run, groups of rats were trained by either downhill (-16 degrees), level (0 degrees), or uphill (+16 degrees) running (16 m . min -1) for 30 min/day. Training duration was either 5 days or 1 day. A training effect (i.e., reduced muscle injury) was indicated if muscle G-6-PDase or plasma CPK activity in a trained group following the 90-min downhill run was not different from that of nonexercised control animals and/or if it was lower than that of nontrained runners. A significant training effect was achieved in all three muscles with 5 days of either downhill or level training, but only in S after 5 days of uphill training. Elevation of plasma CPK activity was prevented by 5 days of training on all three inclines.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between anaerobic threshold and electromyographic fatigue threshold in college women

The purpose of this study was to investigate the relationship between anaerobic threshold (Th(an)) and muscle fatigue threshold (EMGFT) as estimated from electromyographic (EMG) data taken from the quadriceps muscles (vastus lateralis) during exercise on a cycle ergometer. The subjects in this study were 20 female college students, including highly trained endurance athletes and untrained sedentary individuals, whose fitness levels derived from their maximal oxygen consumption ranged from 24.9 to 62.2 ml.kg-1.min-1. The rate of increase in integrated EMG (iEMG) activity as a function of time (iEMG slope) was calculated at each of four constant power outputs (350, 300, 250, 200 W), sufficiently high to bring about muscle fatigue. The iEMG slopes so obtained were plotted against the exercise intensities imposed, resulting in linear plots which were extrapolated to zero slope to give an intercept on the power axis which was in turn interpreted as the highest exercise intensity sustainable without electromyographic evidence of neuromuscular fatigue (EMGFT). The Th(an) was estimated from gas exchange parameters during an incremental exercise test on the same cycle ergometer. The mean results indicated that oxygen uptake (VO2) at Than was 1.39 l.min-1, SD 0.44 and VO2 at EMGFT was 1.33 l.min-1, SD 0.57. There was no significant difference between these mean values (P greater than 0.05) and there was a highly significant correlation between VO2 at Than and VO2 at EMGFT (r = 0.823, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Walking slope and heavy backpack loads affect torso muscle activity and kinematics

The independent effects of sloped walking or carrying a heavy backpack on posture and torso muscle activations have been reported. While the combined effects of sloped walking and backpack loads are known to be physically demanding, how back and abdominal muscles adapt to walking on slopes with heavy load is unclear. This study quantified three-dimensional pelvis and torso kinematics and muscle activity from longissimus, iliocostalis, rectus abdominis, and external oblique during walking on 0° and ± 10° degree slopes with and without backpack loads using two different backpack configurations (hip-belt assisted and shoulder-borne). Iliocostalis activity was greater during downhill and uphill compared to level walking, but longissimus was only greater during uphill. Rectus abdominis activity was greater during downhill and uphill compared to level, while external oblique activity decreased as slopes progressed from down to up. Longissimus, but not iliocostalis, activity was reduced during both backpack configurations compared to walking with no pack. Hip-belt assisted load carriage required less rectus abdominis activity compared to using shoulder-borne only backpacks; however, external oblique was not influenced by backpack condition. Our results revealed different responses between iliocostalis and longissimus, and between rectus abdominis and external obliques, suggesting different motor control strategies between anatomical planes.     

Zigzagging: theoretical insights on climbing strategies

Human and animal trails on steep hillsides often exhibit dramatic switchbacks and shortcuts. Helbing et al. have recently examined the emergence of human trail systems on flat terrains while Minetti and Margaria established the effect of gradients on human metabolic efficiency. In this paper we use these ideas to develop a semi-quantitative theoretical model of the behaviour of humans moving on a terrain with relief. The model determines the direction of movement by minimising metabolic cost per unit of distance in a desired direction. The structure of the theory resembles the Landau Theory of Phase Transitions, much used in theoretical physics. We find that both hairpin bends (switchbacks) and shortcuts appear as efficient strategies for downhill walkers, while uphill walkers retain switchbacks. For weakly inclined slopes, the best strategy involves walking directly uphill or downhill. For sufficiently steep slopes, however, we find that the best strategy should undergo a transition to a broken symmetry solution corresponding to the switchback trail patterns typical of rugged environments. The critical slope at which this transition takes place should be less steep for uphill and downhill walkers. The theory should be amenable to empirical investigation. Amongst other applications, this model will enable us to generalize the work of previous authors to real landscapes, eventually permitting the reconstruction of ancient patterns of movement in archaeological landscapes.     

EFFECTS OF DOWNHILL AND UPHILL EXERCISES OF EQUIVALENT SUBMAXIMAL INTENSITIES ON SELECTED BLOOD CYTOKINE LEVELS AND BLOOD CREATINE KINASE ACTIVITY

The study was aimed at comparing the effects of concentric (CONC) and eccentric (ECC) exercises of equivalent (in terms of relative work load expressed as a percentage of VO₂max) moderate intensity on selected blood cytokine levels and blood creatine kinase (CK) activity. Twenty recreationally active healthy young male volunteers were randomized between two groups that performed a single 1 h bout of CONC (uphill running) or ECC (downhill running) exercise at 60% of the respective individual VO₂max. Venous blood taken 1 h before, at the end, and 24 h after the exercise was processed for plasma and analyzed for CK activity and IL-6, IL-1β and TNFα levels. There was no between-group difference in these cytokines prior to or just after the exercise, and in pre-exercise CK activity. The cytokines elevated significantly and similarly in both groups during the exercise, with no significant change in CK activity. Twenty-four hours later, CK activity and IL-6 were at pre-exercise levels in the CONC group, but showed further major increases in the ECC group, resulting in marked between-group differences in these indices. Changes in IL-1β and TNFα levels during the recovery period showed only minor differences between the study groups and produced no significant between-group difference in these cytokines. However, IL-1β level normalized in the ECC but not in the CONC group. The study suggests that moderate intensity ECC exercise compared to CONC exercise of equivalent relative work load results in considerably greater muscle damage and its related elevation in circulating IL-6, but it does not cause a major systemic inflammatory response.     

Sex differences in oxidative stress after eccentric and concentric exercise

Objectives: Comparison of redox balance changes in the blood of women and men as a result of submaximal eccentric (ECC) and concentric (CONC) efforts.

Methods: 10 women and 10 men performed three 45-minute submaximal treadmill runs at constant velocities (downhill run – ECC, uphill run – CONC and level run). Prior to the 45-minute exercises, after their completion and following 24 hours of recovery, the concentration of lactate, oxidized low-density lipoprotein (ox-LDL), 3-nitrotyrosine, uric acid (UA) and the white blood cell count (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte content in the blood were determined.

Results: In women, the ox-LDL increased significantly 10 minutes and 24 hours following ECC (P?P?P?P?Discussion: ECC cause impaired redox balance only in women. Due to the increase in antioxidant capacity of the blood without accompanying oxidative damage to macromolecules, for both sexes, it is recommended to perform concentric running efforts at the highest possible subliminal intensity.     

Mechanical work performed by the individual legs during uphill and downhill walking

Previous studies of the mechanical work performed during uphill and downhill walking have neglected the simultaneous negative and positive work performed by the leading and trailing legs during double support. Our goal was to quantify the mechanical work performed by the individual legs across a range of uphill and downhill grades. We hypothesized that during double support, (1) with steeper uphill grade, the negative work performed by the leading leg would become negligible and the trailing leg would perform progressively greater positive work to raise the center of mass (CoM), and (2) with steeper downhill grade, the leading leg would perform progressively greater negative work to lower the CoM and the positive work performed by the trailing leg would become negligible. 11 healthy young adults (6 M/5 F, 71.0±12.3 kg) walked at 1.25 m/s on a dual-belt force-measuring treadmill at seven grades (0, ±3, ±6, ±9°). We collected three-dimensional ground reaction forces (GRFs) and used the individual limbs method to calculate the mechanical work performed by each leg. As hypothesized, the trailing leg performed progressively greater positive work with steeper uphill grade, and the leading leg performed progressively greater negative work with steeper downhill grade (p<0.005). To our surprise, unlike level-ground walking, during double support the leading leg performed considerable positive work when walking uphill and the trailing leg performed considerable negative work when walking downhill (p<0.005). To understand how humans walk uphill and downhill, it is important to consider these revealing biomechanical aspects of individual leg function and interaction during double support.     

Eccentric exercise-induced injury to rat skeletal muscle

These experiments were designed to study skeletal muscle pathology resulting from eccentric-biased exercise in rats. The effects on the muscles of running on a treadmill on a 0 degrees incline (similar amounts of concentric and eccentric contractions), down a 16 degrees incline (primarily eccentric contractions), and up a 16 degrees incline (primarily concentric contractions) at 16 m . min-1 for 90 min were assessed by following postexercise changes in 1) plasma creatine kinase and lactate dehydrogenase activities, 2) glucose-6-phosphate dehydrogenase (G-6-PDase) activity (bio- and histochemically) in the physiological extensor muscles, and 3) histological appearance of the muscles. The data indicate the following. 1) Whereas all exercise protocols resulted in elevations of plasma enzymes immediately after running, only eccentric exercise caused late phase elevations 1.5-2 days postexercise. 2) Significant increases in muscle G-6-PDase activity, which were always associated with accumulations of mononuclear cells, always occurred within some muscles of each extensor group 1-3 days following downhill and uphill running and did not occur following level running; the increases in activity were usually of lower magnitude in the muscles of uphill runners than in those of downhill runners; the deeply located, predominantly slow-twitch muscles were most affected by both down- and uphill running. 3) Muscle histology demonstrated localized disruption of normal banding patterns of some fibers immediately after exercise and accumulations of macrophages in the interstitium and in some (less than 5%) muscle fibers by 24 h postexercise in the deep slow muscles of the antigravity groups. Although the data generally indicated that eccentric exercise causes greater injury to the muscles, questions remain.