Immune parameters in athletes before and after strenuous exercise

Secretory IgA levels were studied in nationally ranked Nordic skiers before and after the national cross-country races held in February 1981. Comparing the skiers with age-matched controls, there was a significantly lower level of salivary IgA before the race. Concentrations of IgA decreased further following the competition (50 km for males; 20 km for females) to very low levels. There also were a significant increase in the percentage of B lymphocytes and a decrease in the null population (non-T, non-B) in the athletes after the race compared with the controls. The mechanism responsible for these changes is unknown, but the low salivary IgA levels may result from depletion of nasal fluid and/or malfunction of the mucosal plasma cells due to a decreased temperature in the mucous membranes. We speculated that a temporary antibody deficiency on the mucosal surface might lead to a susceptibility to acquiring viral and bacterial infections, especially during the interval immediately following strenuous exercise.     

Changes in blood cell response following strenuous physical exercise

Summary The generation of tumour necrosis factor (TNF) and tissue factor activity in lipopolysaccharide (LPS) stimulated blood were studied in 25 healthy subjects before and after physical exercise of different intensities. Of the subjects a group of 9 were athletes who trained once to twice every day of the week, a second group of 8 exercised 3–7 times a week, and a third group of 8 exercised 4–5 times a month. The production of TNF in freshly drawn LPS stimulated blood in heparin, drawn from top athletes at rest was significantly lower than in the other subjects. The LPS induced concentrations of TNF- of 2.73 (SEM 1.05) ng · ml^–1 in the blood of the top athletes compared to 5.08 (SEM 0.7) ng · ml^–1 and 7.6 (SEM 1.6) ng · ml^–1, respectively, in the other two groups. The group that trained the least had the highest values. Immediately after exercise, the monocytes appeared to be less responsive to LPS stimulation, as a reduction of 47%–48% was observed in the top athletes and in the other group of well-trained individuals. The group that trained the least, which was also subjected to the least stressful exercise, had a 33% reduction in TNF production. Within 6 h the TNF concentration was back to pre-exercise values. Within 6 h the TNF concentration was back to pre-exercise values. In contrast to TNF production, the LPS induced tissue factor activity of monocytes was significantly higher in the top athletes and in the group of well-trained individuals when measured immediately after 10 min of exercise compared to pre-exercise values. The increase in tissue factor activity was probably a reflection of simultaneous granulocyte- and platelet activation which is known to enhance LPS induced tissue factor activity in monocytes. Except for the period immediately after exercise, there was a significant correlation between LPS induced TNF and tissue factor activity in the whole blood of the participants. In conclusion, hard physical training appeared to suppress the availability of TNF in stimulated blood. This was even more pronounced immediately after strenuous physical exercise.     

Blood lactate response to overtraining in male endurance athletes

Many physiological markers vary similarly during training and overtraining. This is the case for the blood lactate concentration ([La⁻]_b), since a right shift of the lactate curve is to be expected in both conditions. We examined the possibility of separating the changes in training from those of overtraining by dividing [La⁻]_b by the rating of perceived exertion ([La⁻]_b/RPE) or by converting [La⁻]_b into a percentage of the peak blood lactate concentration ([La⁻]_b,peak). Ten experienced endurance athletes increased their usual amount of training by 100% within 4 weeks. An incremental test and a time trial were performed before (baseline) and after this period of overtraining, and after 2 weeks of recovery (REC). The [La⁻]_b and RPE were measured during the recovery of each stage of the incremental test. We diagnosed overtraining in seven athletes, using both physiological and psychological criteria. We found a decrease in mean [La⁻]_b,peak from baseline to REC [9.64 (SD 1.17), 8.16 (SD 1.31) and 7.69 (SD 1.84) mmol · l⁻¹, for the three tests, respectively; P < 0.05] and a right shift of the lactate curve. Above 90% of maximal aerobic speed (MAS) there was a decrease of mean [La⁻]_b/RPE from baseline to REC [at 100% of MAS of 105.41 (SD 17.48), 84.61 (SD 12.56) and 81.03 (SD 22.64) arbitrary units, in the three tests, respectively; P < 0.05), but no difference in RPE, its variability accounting for less than 25% of the variability of [La⁻]_b/RPE (r=0.49). Consequently, [La⁻]_b/RPE provides little additional information compared to [La⁻]_b alone. Expressing [La⁻]_b as a %[La⁻]_b,peak resulted in a suppression of the right shift of the lactate curve, suggesting it was primarily the consequence of a decreased production of lactate by the muscle. Since the right shift of the curve induced by optimal training is a result of improved lactate utilization, the main difference between the two conditions is the decrease of [La⁻]_b,peak during overtraining. We propose retaining it as a marker of overtraining for long duration events, and repeating its measurement after a sufficient period of rest to make the distinction with overreaching. Accepted: 26 September 2000     

Some characteristics of the proteinase—Inhibitor systems in adaptive response to strenuous exercise

In rats, adaptation to strenuous exercise was accompanied by phasic changes in the activities of the kallikrein-kinin system, elastase-like proteinases, and proteinase inhibitors, and total antioxidant activity in the serum, myocardium, liver, and cerebral cortex. After 30-min physical exercises, activity of the kallikrein-kinin system decreased in the serum and increased in tissue with parallel activation of elastase-like proteinases in the myocardium and cerebral cortex. After 3-h exercises the activity of the kallikrein-kinin system showed some indications of exhaustion, especially in the myocardium and cerebral cortex. Activities of elastase-like proteinases tended to normal due to activation of α₁-proteinase inhibitor and normalization of total antioxidant activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 529–532, May, 1999     

The cardio-vascular response during exercise in athletes

Summary In an exercise test of 160 w intensity, accomplished by 16 athletes, a comparative study was carried out on the following heart rate and arterial pressure indices: total cardiac work cost/w, total cardiac recovery cost/w, the ratio of the former to the latter, cardiac work cost above rest/w, cardiac recovery cost above rest and the ratio of the former to the latter, the cardiac work cost above rest/w in the last minute, cardiac recovery cost, the sum of P_1,2,3 and P_{av. 1,2,3}, the ratio of increase of systolic pressure during work to the number of watts performed, the ratio of this pressure increase to the heart rate increase, the ratio of differential pressure during work to: the heart rate in the 10. min of work, increase in the heart rate during work and number of watts achieved.     

Effects of chronic dobutamine administration on the response to acute exercise in dogs

The effects of chronic dobutamine administration on haemodynamic and metabolic responses to submaximal and maximal exercise were studied in dogs. Dobutamine was infused at a rate of 40 micrograms/kg min-1, 2 h day-1, 5 days week-1 for a period of 6 weeks. Acute infusion of dobutamine for 1 h increased heart rate by 73 +/- 30 beats min-1 and cardiac output by 143 +/- 141 ml/min kg-1, reduced mean arterial blood pressure by 12 +/- 10 mmHg and arterial-venous O2 difference by 1.5 +/- 1 vol%. Maximal oxygen consumption, heart rate, stroke volume, cardiac output and arterial-venous O2 difference were unchanged after 6 weeks of treatment. Reductions in heart rate at rest and during submaximal exercise following chronic dobutamine treatment were small and significant only at the lowest exercise level studied. Mixed venous lactate concentrations measured at rest, during submaximal and maximal exercise and at 2 min of recovery were not different after dobutamine treatment. Chronic dobutamine infusion did not change the citrate synthase activity in the lateral gastrocnemius muscle. These results suggest that chronic dobutamine therapy in healthy dogs does not produce aerobic training responses.     

Prolonged wakefulness alters neuronal responsiveness to local electrical stimulation of the neocortex in awake rats

Prolonged wakefulness or a lack of sleep lead to cognitive deficits, but little is known about the underlying cellular mechanisms. We recently found that sleep deprivation affects spontaneous neuronal activity in the neocortex of sleeping and awake rats. While it is well known that synaptic responses are modulated by ongoing cortical activity, it remains unclear whether prolonged waking affects responsiveness of cortical neurons to incoming stimuli. By applying local electrical microstimulation to the frontal area of the neocortex, we found that after a 4 h period of waking the initial neuronal response in the contralateral frontal cortex was stronger and more synchronous, and was followed by a more profound inhibition of neuronal spiking as compared with the control condition. These changes in evoked activity suggest increased neuronal excitability and indicate that, after staying awake, cortical neurons become transiently bistable. We propose that some of the detrimental effects of sleep deprivation may be a result of altered neuronal responsiveness to incoming intrinsic and extrinsic inputs.     

The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats

The purposes of this study were to investigate the effects of strenuous exercise on apoptosis of the gastrocnemius and soleus muscle fibers and clarify the role of oxidative metabolism in the strenuous exercise-induced apoptosis. The experiment was designed with 49 (n = 49) male, 24-week-old, L. Wistar albino rats. Strenuous exercise model was applied to 42 (n = 42) rats and seven (n = 7) rats served as rested controls. All rats were randomly assigned to one of the following groups (n = 7): rested control (C), immediately after exercise (0 h) and 3, 6, 12, 24, and 48 h after exercise. Apoptotic nuclei were shown by single stranded DNA (ssDNA) determination. Oxidative damage in mitochondrial fractions of the muscle tissues was evaluated by malondialdehyde (MDA) levels and reduced/oxidized glutathione (GSH/GSSG) ratios. Caspase-9, -8 and -3 activities and the level of cytochrome c (Cyt c) were measured in the cytosolic fractions of muscle tissues to follow mitochondrial-dependent (intrinsic) or ligand-mediated death receptor (extrinsic) pathways of apoptosis. Plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were also determined. Based on our results, apoptosis is significantly triggered in muscle fibers by strenuous exercise (P < 0.05). Apoptosis in the soleus muscle tissues mostly depends on the intrinsic pathway and may be triggered by increased oxidative stress. In contrast, extrinsic pathway of apoptosis was predominant in the gastrocnemius muscle and increases of TNF-α and IL-6 may play a significant role.     

Muscle afferent contributions to the cardiovascular response to isometric exercise

The cardiovascular response to isometric exercise is governed by both central and peripheral mechanisms. Both metabolic and mechanical stresses on the exercising skeletal muscle produce cardiovascular change, yet it is often overlooked that the afferent signal arising from the muscle can be modified by factors other than exercise intensity. This review discusses research revealing that muscle fibre type, muscle mass and training status are important factors in modifying this peripheral feedback from the active muscles. Studies in both animals and humans have shown that the pressor response resulting from exercise of muscle with a faster contractile character and isomyosin content is greater than that from a muscle of slower contractile character. Athletic groups participating in training programmes that place a high anaerobic load on skeletal muscle groups show attenuated muscle afferent feedback. Similarly, longitudinal studies have shown that specific local muscle training also blunts the pressor response to isometric exercise. Thus it appears that training may decrease the metabolic stimulation of muscle afferents and in some instances chronic exposure to the products of anaerobic metabolism may blunt the sensitivity of the muscle metaboreflex. There may be surprising parallels between the local muscle conditions induced in athletes training for longer sprint events (e.g. 400 m) and by the low-flow conditions in, for example, the muscles of chronic heart failure patients. Whether their similar attenuations in muscle afferent feedback during exercise are due to decreased metabolite accumulation or to a desensitization of the muscle afferents is not yet known.     

Response of erythrocytic 2,3-diphosphoglycerate to strenuous exercise

Summary Since increases of erythrocytic 2,3-diphosphoglycerate (2,3-DPG) have been shown to enhance the release of oxygen from hemoglobin, experiments were designed to evaluate the response of 2,3-DPG to two different workloads in 13 fasted human subjects. No significant mean change in 2,3-DPG was found following 16 min of strenuous exercise on a bicycle ergometer, but when the subjects were subjected later to a greater workload for 20 min, there was a significant mean decrease in 2,3-DPG despite much individual variation. In addition, there was a significant positive correlation of 2,3-DPG reduction with increases in postexercise lactate, and a significant inverse correlation of oxygen consumption during exercise with postexercise lactate. The data suggest that the 2,3-DPG mechanism may not be compensating in exercise when the workload requires a preponderance of anaerobic metabolism promoting lactacidaemia.     

Mapping the central neurocircuitry that integrates the cardiovascular response to exercise in humans

There are abundant animal data attempting to identify the neural circuitry involved in cardiovascular control. Translating this research into humans has been made possible using functional neurosurgery during which deep brain stimulating electrodes are implanted into various brain nuclei for the treatment of chronic pain and movement disorders. This not only allows stimulation of the human brain, but also presents the opportunity to record neural activity from various brain regions. This symposium review highlights key experiments from the past decade that have endeavoured to identify the neurocircuitry responsible for integrating the cardiovascular response to exercise in humans. Two areas of particular interest are highlighted: the periaqueductal grey and the subthalamic nucleus. Our studies have shown that the periaqueductal grey (particularly the dorsal column) is a key part of the neurocircuitry involved in mediating autonomic changes adapted to ongoing behaviours. Emerging evidence also suggests that the subthalamic nucleus is not only involved in the control of movement, but also in the mediation of cardiovascular responses. Although these sites are unlikely to be the 'command' areas themselves, we have demonstrated that the two nuclei have the properties of being key integrating sites between the feedback signals from exercising muscle and the feedforward signals from higher cortical centres.     

Role of arterial baroreceptors in mediating cardiovascular response to exercise.

The role played by the major arterial baroreceptor reflexes in the cardiovascular response to exercise was examined by comparing the responses of untethered conscious dogs instrumented for the measurement of aortic pressure and cardiac output with those of dogs with total arterial barorecptor denervation (TABD). Moderately severe levels of exercise (12 mph) in intact dogs increased cardiac output from 111 +/- 17 ml/kg per min, increased heart rate from 101 +/- 5 to 265 +/- 8 beats/min, and reduced total peripheral resistance from 0.039 +/- 0.003 to 0.015 +/- 0.002 mmHg/ml per min. Dogs with TABD responded in a very similar fashion; exercise increased cardiac output from 119 +/- 8 to 356 /+- 23 ml/kg per min, increased heart rate from 122 +/- 7 to 256 +/- 5 beats/min, and decreased total peripheral resistance from 0.042 +/- 0.005 to +/- 0.015 +/- 0.001 mmHg/ml per min. The reflex heart rate responses to intravenous bolus doses of methoxamine were also examined in intact animals, both at rest and during exercise. Methoxamine caused striking bradycardia at rest, but little bradycardia during exercise. These results suggest that the arterial baroreceptor reflex is normally turned off during severe exercise and thus does not modify significantly the cardiovascular response to exercise.     

Stroke volume response to progressive exercise in athletes engaged in different types of training

Summary Using the impedance cardiography method, heart rate ( _c) matched changes on indexed stroke volume (SI) and cardiac output (CI) were compared in subjects engaged in different types of training. The subjects consisted of untrained controls (C), volleyball players (VB) who spent about half of their training time (360 min · week^–1) doing anaerobic conditioning exercises and who had a maximal oxygen uptake ( ) 41% higher than the controls, and distance runners (D) who spent all their training time (366 min·week^–1) doing aerobic conditioning exercises and who had a 26% higher than VB. The subjects performed progressive submaximal cycle ergometer exercise (10 W·min^–1) up to _c of 150 beats·min^–1. In group C, SI had increased significantly (P<0.05) at _c of 90 beats·min^–1 ( + 32%) and maintained this difference up to 110 beats·min^–1, only to return to resting values on reaching 130 beats·min^–1 with no further changes. In group VB, SI peaked (+ 54%) at _c of 110 beats·min^–1, reaching a value significantly higher than that of group C, but decreased progressively to 22010 of the resting value on reaching 150 beats·min^–1. In group D, SI peaked at _c of 130 beats·min^–1 (+ 54%), reaching a value significantly higher than that of group VB, and showed no significant reduction with respect to this peak value on reaching 150 beats·min^–1. As a consequence, the mean CI increase per _c unit was progressively higher in VB than in C (+46%) and in D than in VB (+ 105%). It was concluded that thef _c value at which SI ceased to increase during incremental exercise was closely related to the endurance component in the training programme.     

Fibrinolytic response to moderate exercise in young male diabetics and non-diabetics

The euglobulin lysis time was measured in 25 young male insulin-dependent diabetics and 25 age- and sex-matched healthy controls before and after a standardized moderate treadmill exercise procedure. There was a statistically significant mean shorter resting euglobulin lysis time in the diabetic group but their ability to respond to the exercise procedure was significantly impaired. It is suggested that this impaired fibrinolytic reactivity may be related to the diminished vaso-active reactivity previously reported in young diabetics.     

The interstitial fluid content in working muscle modifies the cardiovascular response to exercise

Summary The volume of interstitial fluid in the limbs varies considerably, due to hydrostatic effects. As signals from working muscle, responsible for much of the cardiovascular drive, are assumed to be transmitted in this compartment, blood pressure and heart rate could be affected by local or systemic variations in interstitial hydration. Using a special calf ergometer, eight male subjects performed rhythmic aerobic plantar flexions in a supine position with dependent calves for periods of 7 min. During exercise heart rate, blood pressure, oxygen uptake (VO₂) and blood lactate concentrations were measured in two different tests, one before and after interstitial calf dehydration through limb elevation for 25 min, compared to the other, a control with unaltered fluid volume in a maintained working position. Impedance plethysmography showed calf volume to be stabilized in the control position. Leg elevation by passive hip flexion to 90° resulted in a fast (vascular) volume decrease lasting <2 min, followed by a slow linear fluid loss from the interstitial compartment. Then, when returned to the control position, adjustment of vascular volume was completed within 2 min and exercise could be performed with dehydration remaining in the interstitium only. Cadiovascular response was identical at the start of both tests. However, exercising with dehydrated calves elicited a significantly larger increase in heart rate compared to the control, whereasVO₂ was identical. The blood pressure response was shown to be only slightly enhanced. Structural interstitial features varying with hydration, most likely chemical or mechanical ones, may have been responsible for this amplification of signals.     

Prolonged exercise does not cause lymphocyte DNA damage or increased apoptosis in well-trained endurance athletes

Recent research has demonstrated that lymphocyte apoptosis sensitivity appears to be related to training status and exercise intensity. This work investigated the effect of prolonged, submaximal treadmill running on percentage (%) apoptosis, % necrosis and DNA strand breaks in lymphocytes and related these to changes in total lymphocyte and blood cortisol concentrations in well-trained runners. Venous blood samples (n = 14) were taken immediately before (PRE), immediately after (IPE) and 3 h after (3PE) 2.5 h of treadmill running at 75% of VO₂ max from eight well-trained male endurance athletes (age 34.2 ± 2.44 years) and analysed for cellular content and serum cortisol concentrations. Lymphocytes were isolated from whole blood and % apoptotic and necrotic cell were detected by flow cytometry using Annexin V-FITC and propidium iodide uptake. DNA strand breaks were measured by single-cell gel electrophoresis. Despite a significant (P < 0.001) exercise-induced increase in mean serum cortisol concentrations and reduction in lymphocyte counts, the mean % Annexin-V positive cells (13.3 ± 6.78 in PRE, 11.3 ± 5.51 in IPE and 12.8 ± 6.75 in 3PE samples) were not significantly different at the three time-points (P > 0.05). Mean DNA strand breaks in the lymphocytes also did not change significantly (P > 0.05) rising from 25.7 ± 2.16 to 26.9 ± 1.89 and 27.1 ± 1.38 μm in IPE and 3PE samples, respectively. The exercise-induced changes in total blood lymphocyte counts and cortisol concentrations did not result in a significant change in % apoptotic lymphocytes or DNA strand breaks in the endurance-trained athletes during this prolonged, submaximal exercise.     

Biphasic changes in leukocytes induced by strenuous exercise

Summary Seven healthy male volunteers participated in short- (STR, 1.7 km), middle- (MTR, 4.8 km) and long- (LTR, 10.5 km) term runs at a speed close to their maximum. A prompt mobilization of white cells, and lymphocytes in particular, appeared following the exercise. The initial increase in the number of lymphocytes was succeeded by a significant decrease [(P < 0.03) lymphopenia), which on average was 32%–39% of the pre-exercise values in all groups. A close correlation was found between the initial increase in plasma cortisol concentration after exercise and the subsequent lymphopenia. A modest enhancement in the number of granulocytes immediately after the exercise was accompanied by a comprehensive increase in polymorphonuclear (PMN) elastase concentration accounting for 78.6%, SEM 16.3%, 140.7%, SEM 31.8% and 241.3%, SEM 48.1% in the STR, MTR and LTR groups. No correlation was found between granulocyte number and the plasma PMN elastase concentration. A delayed granulocytosis was noted in all subjects, reaching a peak between 2 and 4 h after the exercise. The magnitude of the granulocytosis varied among subjects and peak values of the number of circulating granulocytes were found to be 5.7 × 10⁹ cells · 1^–1, SEM 0.5, 6.7 × 10⁹ cells · 1^–1, SEM 0.6 and 8.8 × 10⁹ cells · 1^–1, SEM 0.5 in STR, MTR and LTR respectively, whereas the mean baseline value was 3.6 × 10⁹ cells · 1^–1, SEM 0.4. The neutrophilic granulocytosis was not accompanied by a corresponding enhancement in PMN elastase concentration. The plasma cortisol concentration reached a peak 30 min after exercise and declined below the control level in 4 h. Neither the initial increase, nor the subsequent decrease in plasma cortisol concentration were found to be essential for the magnitude of the delayed leukocytosis.     

Atrial natriuretic factor during exercise in male endurance athletes: effect of training

Nine male endurance runners were evaluated with bicycle exercise testing before a training break of 3 weeks duration, and 0, 2 and 4 weeks after resumption of training to assess the effects of training on resting and exercise plasma atrial natriuretic factor (ANF) measured at 50% and 100% of predetermined maximal workload. Maximal oxygen uptake and lean body mass (LBM) were calculated at each time point. Maximal oxygen uptake decreased during training break, but rose 4 weeks after resumption of training (P less than 0.01). LBM was unchanged after inactivity, but rose after resumption of training (P less than 0.01). Plasma ANF at rest did not change throughout the experiment. ANF levels rose after training break at maximal workload (P less than 0.05), and decreased 4 weeks after resumption of training, but only at submaximal workload (P less than 0.05). No correlations between systolic blood pressure, mean blood pressure or heart rate and ANF could be demonstrated. These results indicate that the haemodynamic changes associated with endurance training are reflected in plasma ANF levels during exercise, but not at rest. The full adaptation of ANF release to training probably requires more time than the 4 weeks reported for the haemodynamic adjustments.