Category: Exercise

Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls

Abstract:

PURPOSE: Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

METHODS: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise.

RESULTS: Basal HSP27 was higher among CFS patients than in controls (0.54 +/- 0.13 vs. 0.19 +/- 0.06, mean +/- SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 +/- 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 +/- 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 +/- 0.40 vs. 1.32 +/- 0.46; P < 0.05), and for HSP90 (0.34 +/- 0.09 vs. 0.49 +/- 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 +/- 0.27) and day 7 (1.24 +/- 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 +/- 0.06) (P < 0.05, respectively).

CONCLUSION: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

 

Source: Thambirajah AA, Sleigh K, Stiver HG, Chow AW. Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Clin Invest Med. 2008 Dec 1;31(6):E319-27. https://www.ncbi.nlm.nih.gov/pubmed/19032901

 

Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome

Abstract:

Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise.

We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs.

At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (> or = 2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups.

In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

 

Source: Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol Med. 2009 Jan-Feb;15(1-2):34-42. doi: 10.2119/molmed.2008.00098. Epub 2008 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/ (Full article)

 

Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome

Abstract:

This study examined the effects of maximal incremental exercise on cerebral oxygenation in chronic fatigue syndrome (CFS) subjects. Furthermore, we tested the hypothesis that CFS subjects have a reduced oxygen delivery to the brain during exercise.

Six female CFS and eight control (CON) subjects (similar in height, weight, body mass index and physical activity level) performed an incremental cycle ergometer test to exhaustion, while changes in cerebral oxy-haemoglobin (HbO2), deoxy-haemoglobin (HHb), total blood volume (tHb = HbO2 + HHb) and O2 saturation [tissue oxygenation index (TOI), %)] was monitored in the left prefrontal lobe using a near-infrared spectrophotometer. Heart rate (HR) and rating of perceived exertion (RPE) were recorded at each workload throughout the test.

Predicted VO2peak in CFS (1331 +/- 377 ml) subjects was significantly (P < or = 0.05) lower than the CON group (1990 +/- 332 ml), and CFS subjects achieved volitional exhaustion significantly faster (CFS: 351 +/- 224 s; CON: 715 +/- 176 s) at a lower power output (CFS: 100 +/- 39 W; CON: 163 +/- 34 W). CFS subjects also exhibited a significantly lower maximum HR (CFS: 154 +/- 13 bpm; CON: 186 +/- 11 bpm) and consistently reported a higher RPE at the same absolute workload when compared with CON subjects. Prefrontal cortex HbO2, HHb and tHb were significantly lower at maximal exercise in CFS versus CON, as was TOI during exercise and recovery.

The CFS subjects exhibited significant exercise intolerance and reduced prefrontal oxygenation and tHb response when compared with CON subjects. These data suggest that the altered cerebral oxygenation and blood volume may contribute to the reduced exercise load in CFS, and supports the contention that CFS, in part, is mediated centrally.

 

Source: Patrick Neary J, Roberts AD, Leavins N, Harrison MF, Croll JC, Sexsmith JR. Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome. Clin Physiol Funct Imaging. 2008 Nov;28(6):364-72. doi: 10.1111/j.1475-097X.2008.00822.x. Epub 2008 Jul 29. https://www.ncbi.nlm.nih.gov/pubmed/18671793

 

Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial

Abstract:

OBJECTIVE: It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with chronic fatigue syndrome.

DESIGN: An uncontrolled clinical trial (semi-experimental design).

SETTING: Outpatient clinic of a university department.

SUBJECTS: Twenty-four patients with chronic fatigue syndrome.

INTERVENTIONS: Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an intensity where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio = 1.0 derived from a previous submaximal exercise test and for a duration calculated from how long each patient felt they were able to walk.

MAIN OUTCOME MEASURES: The Short Form 36 Health Survey or SF-36, the Chronic Fatigue Syndrome Symptom List, and the Chronic Fatigue Syndrome -Activities and Participation Questionnaire were filled in prior to, immediately after and 24 hours after exercise.

RESULTS: The fatigue increase observed immediately post-exercise (P= 0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (P=0.03). Fourteen of the 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score > or =10); 6 indicated that the exercise bout had slightly worsened their health status, and 2 had a clinically meaningful decrease in vitality (change of SF-36 vitality score > or =20). There was no change in activity limitations/participation restrictions.

CONCLUSION: It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with chronic fatigue syndrome, but was unable to prevent short-term symptom increases.

 

Source: Nijs J, Almond F, De Becker P, Truijen S, Paul L. Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial. Clin Rehabil. 2008 May;22(5):426-35. Doi: 10.1177/0269215507084410. https://www.ncbi.nlm.nih.gov/pubmed/18441039

 

Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations

Abstract:

Controversy regarding the aetiology and treatment of patients with chronic fatigue syndrome continues among the medical professions. The Cochrane Collaboration advises practitioners to implement graded exercise therapy for patients with chronic fatigue syndrome using cognitive behavioural principles. Conversely, there is evidence that exercise can exacerbate symptoms in chronic fatigue syndrome, if too-vigorous exercise/activity promotes immune dysfunction, which in turn increases symptoms.

When designing and implementing an exercise programme for chronic fatigue syndrome it is important to be aware of both of these seemingly opposing viewpoints in order to deliver a programme with no detrimental effects on the pathophysiology of the condition.

Using evidence from both the biological and clinical sciences, this paper explains that graded exercise therapy for people with chronic fatigue syndrome can be undertaken safely with no detrimental effects on the immune system. Exercise programmes should be designed to cater for individual physical capabilities and should take into account the fluctuating nature of symptoms.

In line with cognitive behaviourally and graded exercise-based strategies, self-management for people with chronic fatigue syndrome involves encouraging patients to pace their activities and respect their physical and mental limitations, with the ultimate aim of improving their everyday functioning.

Comment in: Chronic fatigue syndrome. [J Rehabil Med. 2008]

 

Source: Nijs J, Paul L, Wallman K. Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations. J Rehabil Med. 2008 Apr;40(4):241-7. Doi: 10.2340/16501977-0185. https://www.ncbi.nlm.nih.gov/pubmed/18382818

 

Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study

Abstract:

OBJECTIVE: To review the etiology of chronic fatigue syndrome (CFS) and test hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort.

METHODS: A total of 4779 participants from the Medical Research Council’s National Survey of Health and Development were prospectively followed for the first 53 years of their life with >20 separate data collections. Information was collected on childhood and parental health, atopic illness, levels of physical activity, fatigue, and participant’s weight and height at multiple time points. CFS was identified through self-report during a semistructured interview at age 53 years with additional case notes review.

RESULTS: Of 2983 participants assessed at age 53 years, 34 (1.1%, 95% Confidence Interval 0.8-1.5) reported a diagnosis of CFS. Those who reported CFS were no more likely to have suffered from childhood illness or atopy. Increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

CONCLUSIONS: Individuals who exercise frequently are more likely to report a diagnosis of CFS in later life. This may be due to the direct effects of this behavior or associated personality factors. Continuing to be active despite increasing fatigue may be a crucial step in the development of CFS.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study. Psychosom Med. 2008 May;70(4):488-95. doi: 10.1097/PSY.0b013e31816a8dbc. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378866

 

Comparison of two exercise testing protocols in patients with chronic fatigue syndrome

Abstract:

This study examined whether a linear exercise stress-testing protocol generated different peak exercise performance variables than a stepwise exercise testing protocol in patients with chronic fatigue syndrome (CFS). We conducted a comparative study with patients randomly allocated to one of two exercise testing protocols.

Twenty-eight women with CFS completed two self-reported measures (the CFS Symptom List and the CFS Activities and Participation Questionnaire) and then performed until exhaustion either the linear or the stepwise exercise testing protocol with continuous monitoring of physiological variables (heart rate and oxygen uptake).

At baseline, we found no significant differences in demographic features and health status between groups (p > 0.05). Based on ratio peak workload/peak oxygen uptake, mechanical efficiency was lower among the subjects performing the stepwise protocol (p = 0.002). When we analyzed the mean linear regression slope values between oxygen uptake and workload from each subject’s minute-by-minute exercise data points, we found that mechanical efficiency was lower among the subjects performing the stepwise protocol (p = 0.039). Apart from mechanical efficiency, we found no differences in exercise performance data between groups (p > 0.05).

Our results suggest that the difference between linear and stepwise exercise protocols cannot account for all discrepancies of previous studies on exercise performance data in women with CFS, but they do suggest that the nature of the exercise testing protocol influences mechanical efficiency in these patients. Further study is warranted.

 

Source: Nijs J, Zwinnen K, Meeusen R, de Geus B, De Meirleir K. Comparison of two exercise testing protocols in patients with chronic fatigue syndrome. J Rehabil Res Dev. 2007;44(4):553-9. http://www.rehab.research.va.gov/jour/07/44/4/Nijs.html (Full article)

 

Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS.

We included a consecutive sample of 15 adolescents 12-18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls.

During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls.

Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction.

 

Source: Wyller VB, Saul JP, Walløe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. 2008 Apr;102(6):623-32. Epub 2007 Dec 8. https://www.ncbi.nlm.nih.gov/pubmed/18066580

 

Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance?

Abstract:

AIM: The aetiology, pathophysiology, diagnostic delineation and treatment of chronic fatigue syndrome (CFS) remain a matter of debate. Here some aspects of the debate are elucidated, with a particular focus on the patients’ decreased motor performance.

HYPOTHESIS: The pathophysiological basis of decreased motor performance in CFS may, theoretically, involve three components: (1) a peripheral energetic deficit (impaired oxidative metabolism and/or physical deconditioning); (2) a central perceptual disturbance (higher effort sense or increased ‘interoception’); and (3) a fundamental failure of the neurobiological stress system, leading to an abnormal ‘sickness response’. It is proposed that the first two components may lead to low effort capacity, while the third component may lead to reduced effort tolerance. Although there is evidence for low effort capacity influencing symptoms and functional limitations in CFS, it is assumed that reduced effort tolerance might be the primary disturbance in CFS.

DIAGNOSTIC IMPLICATIONS: Distinguishing low effort capacity and reduced effort tolerance may contribute to a refinement of current diagnostic criteria of CFS and the identification of subgroups.

THERAPEUTIC IMPLICATIONS: The above-mentioned distinction may make it possible to formulate a rationale for an effective implementation and adequate outcome evaluation of rehabilitation strategies in CFS.

RESEARCH IMPLICATIONS: This new heuristic framework may inform future research aimed at disentangling the complex determination of impaired motor performance in CFS, as well as studies aimed at customizing treatment to different subtypes of patients.

 

Source: Van Houdenhove B, Verheyen L, Pardaens K, Luyten P, Van Wambeke P. Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance? Clin Rehabil. 2007 Dec;21(12):1121-42. https://www.ncbi.nlm.nih.gov/pubmed/18042608

 

A real-time assessment of the effect of exercise in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days.

Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1 week before and 2 weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling.

Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise.

 

Source: Yoshiuchi K, Cook DB, Ohashi K, Kumano H, Kuboki T, Yamamoto Y, Natelson BH. A real-time assessment of the effect of exercise in chronic fatigue syndrome. Physiol Behav. 2007 Dec 5;92(5):963-8. Epub 2007 Jul 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170105/ (Full article)